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A Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms

A Phase 3 Study Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms in Postmenopausal Women With an Intact Uterus

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01942668
Acronym
REPLENISH
Enrollment
1845
Registered
2013-09-16
Start date
2013-08-05
Completion date
2016-10-28
Last updated
2019-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Menopause

Keywords

Vasomotor symptoms, Hot flashes, Endometrial protection

Brief summary

This study will be a prospective, randomized, double-blind, placebo-controlled, parallel group, multicenter trial of postmenopausal subjects with an intact uterus.

Detailed description

Postmenopausal subjects with an intact uterus who meet the study entry criteria will be randomized to one of five treatment arms (four active and one placebo) and followed for 12 months. During the Screening period all subjects will be provided with a diary to self-assess the frequency and severity of their vasomotor symptoms. Subjects experiencing a minimum daily frequency of ≥7 (or ≥50 per week) moderate to severe hot flushes will participate in a VMS Substudy during the first 12 weeks of treatment. The Substudy subjects will be stratified by treatment arm within the sites, and only Substudy subjects have the possibility of being randomized to placebo. Subjects who qualify for the study except for experiencing a minimum daily frequency of ≥7 (or ≥50 per week) moderate to severe hot flushes will be stratified within sites to one of the four active treatment arms and followed for 12 months, but will not participate in the VMS Substudy. (However, VMS information will be collected from all subjects during the first 12 weeks of treatment.) All Study Subjects: Postmenopausal women with an intact uterus who seek relief from hot flushes and meet all other inclusion/exclusion criteria are eligible for 12 months of study treatment. VMS Substudy Subjects: A subset of All Study Subjects who have ≥7 per day or ≥50 per week moderate to severe hot flushes (as determined during Screening) are eligible for the 12-week VMS Substudy and for a total of 12 months of study treatment. Clinical evaluations will be performed at the following time points: * Screening Period (Week: - 8.5) (up to -60 Days) * Visit 1 Randomization (Week 0) (Day 1) * Visit 2 Interim (Week 4) * Visit 3 Interim (Week 8) * Visit 4 Interim (Week 12) * Visit 5 Interim (Month 6) * Visit 6 Interim (Month 9) * Visit 7 End of Treatment (Month 12)

Interventions

DRUGEstradiol
DRUGProgesterone
DRUGPlacebo

Sponsors

TherapeuticsMD
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
No

Inclusion criteria

1. Be a female between the ages of 40 and 65 years (at the time of randomization) who is willing to participate in the study, as documented by signing the informed consent form. 2. Be a postmenopausal woman with an intact uterus and a Screening serum estradiol level of ≤50 pg/mL. Postmenopausal is defined herein as: 1. ≥ 12 months of spontaneous amenorrhea, or 2. at least 6 months of spontaneous amenorrhea with a Screening serum FSH level of \>40 mIU/ml, or 3. ≥ 6 weeks postsurgical bilateral oophorectomy. 3. Be seeking treatment or relief for vasomotor symptoms associated with menopause. 4. To participate in the VMS Substudy, a subject must also report ≥7 moderate to severe hot flushes per day, or ≥50 per week, at the baseline assessment during Screening (subjects whose hot flushes are less frequent may still participate as non-Substudy subjects. Note: A minimum of 14 consecutive days of complete hot flush diary data are required during the baseline assessment at Screening, and these consecutive days must occur within the last 14 days prior to the Randomization visit (not counting the Randomization visit day itself). The most recent 7 consecutive days of data prior to randomization (Day -7 to Day -1) will be used to determine the baseline number of mild, moderate and severe hot flushes for each subject. 5. Have a Body Mass Index (BMI) less than or equal to 34 kg/mP2P. (BMI values should be rounded to the nearest integer \[e.g., 34.4 rounds down to 34, while 26.5 rounds up to 27\]). 6. Be willing to abstain from using products (other than study medication) that contain estrogen, progestin, or progesterone throughout study participation. 7. Be judged by the principal or sub-investigator physician as being in otherwise generally good health based on a medical evaluation performed during the Screening period prior to the initial dose of study medication. The medical evaluation findings must include: 1. a normal or non-clinically significant physical examination, including vital signs (sitting blood pressure, heart rate, respiratory rate and temperature). Sitting systolic blood pressure is ≤140 mmHg and diastolic blood pressure ≤90 mmHg at Screening. A subject may be taking up to two antihypertensive medications. 2. a normal or non-clinically significant pelvic examination. 3. a mammogram that shows no sign of significant disease (can be performed within previous 6 months prior to initial dose of study medication). Subjects must have a BI-RADS 1 or 2 to enroll in the study. An incomplete mammogram result, i.e. BI-RADS 0, is not acceptable. The site must obtain a copy of the official report for the subject's study file, and it must be verified that the mammogram itself is available if needed for additional assessment. 4. a normal or non-clinically significant clinical breast examination. An acceptable breast examination is defined as no masses or other findings identified that are suspicious of malignancy. 5. a normal Screening Papanicolaou (Pap) smear. (Subjects with findings of atypical glandular cells \[AGC\], AGUS, ASCUS with high risk HPV type upon reflex testing, LSIL, ASC-H, HSIL, dysplastic cells, or malignant cells must be excluded from randomization.) 6. an acceptable result from an evaluable Screening endometrial biopsy. The endometrial biopsy reports by the two central pathologists at Screening must each specify one of the following: proliferative endometrium; weakly proliferative endometrium; disordered proliferative pattern; secretory endometrium; endometrial tissue other (including benign, inactive or atrophic fragments of endometrial epithelium, glands, stroma, etc); endometrial tissue insufficient for diagnosis; no endometrium identified; or no tissue identified. However, at least one pathologist must identify sufficient tissue to evaluate the biopsy. Additionally, the endometrial biopsy reports by the two central pathologists of Other Findings at Screening must each specify one of the following: endometrial polyp not present; benign endometrial polyp; or polyp other. (See Exclusion criterion #27) 7. a normal or non-clinically significant 12-lead ECG.

Exclusion criteria

* To participate in the study, a subject must NOT: 1. Be currently hospitalized. 2. Have a history of thrombosis of deep veins or arteries or a thromboembolic disorder. 3. Have a history of coronary artery or cerebrovascular disease (e.g., myocardial infarction, angina, stroke, TIA). 4. Have a history of a chronic liver or kidney dysfunction/disorder (e.g., Hepatitis C or chronic renal failure). 5. Have a history of a malabsorption disorder (e.g., gastric bypass, Crohn's disease). 6. Have a history of gallbladder dysfunction/disorders (e.g., cholangitis, cholecystitis), unless gallbladder has been removed. 7. Have a history of diabetes, thyroid disease or any other endocrinological disease. (Subjects with diet-controlled diabetes or controlled hypothyroid disease at Screening are not excluded.) 8. Have a history of estrogen-dependent neoplasia. 9. Have a history of atypical ductal hyperplasia of the breast. 10. Have a finding of clinically significant uterine fibroids at Screening. 11. Have had a uterine ablation. 12. Have a history of undiagnosed vaginal bleeding. 13. Have any history of endometrial hyperplasia, melanoma, or uterine/endometrial, breast or ovarian cancer. 14. Have any history of other malignancy within the last 5 years, with the exception of basal cell (excluded if within 1 year) or non-invasive squamous cell (excluded if within 1 year) carcinoma of the skin. 15. Have a history of any other cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological (e.g., bipolar disorder, schizophrenia, major depressive disorder), or musculoskeletal disease or disorder that is clinically significant in the opinion of the Principal Investigator or Medical Sub-Investigator. 16. Have any of the following clinical laboratory values at Screening: 1. fasting triglyceride of ≥300 mg/dL and/or total cholesterol of ≥300mg/dL 2. positive laboratory finding for Factor V Leiden mutation 3. AST or ALT ≥1.5 times the upper limit of normal (ULN) 4. fasting glucose \>125 mg/dL 17. Be known to be pregnant or have a positive urine pregnancy test. (Note: A pregnancy test is not required for subjects who have had bilateral tubal ligation, bilateral oophorectomy, or are 55 years old or greater and have experienced cessation of menses for at least 1 year.) 18. Have contraindication to estrogen and/or progestin therapy or allergy to the use of estradiol and/or progesterone or any components of the investigational drugs. 19. Use 15 or more cigarettes per day or currently use any electronic cigarettes. 20. Have a history of drug and/or alcohol abuse within one year of start of study. 21. Have used, within 28 days prior to the initial dose of study medication at Visit 1, any medication known to induce or inhibit CYP3A4 enzyme activity that may affect estrogen and/or progestin drug metabolism. (See 48TUSection 4.3U48T) 22. Have used, within 28 days prior to Screening, or plan to use during the study, any prescription or over-the-counter (OTC) medications (including herbal products, such as St. John's Wort) that would be expected to alter progesterone or estrogen activity or is being used to treat vasomotor symptoms. (See Section 4.3U48T) 23. Have used estrogen alone or estrogen/progestin, SERM (selective estrogen receptor modulator), testosterone, or estrogen/testosterone for any of the following time periods: 1. Vaginal nonsystemic hormonal products (rings, creams, gels) within 7 days prior to Screening, or vaginal systemic products (e.g., FemRing) within 28 days prior to Screening. 2. Transdermal estrogen alone or estrogen/progestin products within 8 weeks prior to Screening. 3. Oral estrogen and/or progestin and/or SERM therapy within 8 weeks prior to Screening. 4. Progestational implants, estrogen or estrogen/progestational injectable drug therapy within 3 months prior to Screening. 5. Estrogen pellet therapy or progestational injectable drug therapy within 6 months prior to Screening. 6. Percutaneous estrogen lotions/gels within 8 weeks prior to Screening. 7. Oral, topical, vaginal, patch, implantable or injectable androgen therapy within 8 weeks prior to Screening. 24. Have used an intrauterine device (IUD) within the 12 weeks prior to Screening. 25. For subjects in the VMS Substudy only: use of medication that may affect the outcome of the vasomotor symptom endpoints within 28 days prior to Screening (e.g. SSRIs \[selective serotonin reuptake inhibitors\], SNRIs \[serotonin and norepinephrine reuptake inhibitors\], aldomet, dopaminergic or antidopaminergic drugs, gabapentin, clonidine, or bellergal.) 26. Have any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject from safely participating in the study or complying with protocol requirements. 27. Have a Screening endometrial biopsy sample that is found by both primary pathologists to have endometrial tissue insufficient for diagnosis, no endometrium identified, or no tissue identified. (With the approval of the Medical Monitor, the Screening endometrial biopsy may be repeated once.) 28. Endometrial polyps with atypical nuclei reported by at least 1 central pathologist. 29. Have contraindication to any planned study assessments (e.g., endometrial biopsy). 30. Have participated in another clinical trial within 30 days prior to Screening, have received an investigational drug within the three months prior to the initial dose of study medication, or be likely to participate in a clinical trial or receive another investigational medication during the study. 31. Currently use marijuana.

Design outcomes

Primary

MeasureTime frameDescription
Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)Baseline and Week 4Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)Baseline and Week 4Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Primary Safety Endpoint: Endometrial Protection - HyperplasiaBaseline and Month 12Endometrial biopsies centrally evaluated by 2 primary pathologists using criteria from Blaustein's Pathology text. Pathologists classified bx into 1 of following 3 categories: Cat.1: Non-endometrial malignancy/non-hyperplasia; Cat.2: Endometrial hyperplasia; Cat.3: Endometrial malignancy. Consensus reached when 2 primary pathologist agreed on any of above categories; if primary pathologists disagreed on presence of hyperplasia, result of 3rd pathologist was utilized and final decision regarding presence of hyperplasia was based on diagnosis of majority. If all 3 reads disparate, final diagnosis based on most severe dx. Incidence rate calculated as: I=A/B where I=incidence rate at M12 evaluation, A=all new subjects with biopsies positive for endometrial hyperplasia during study but post-Baseline, B=all subjects w/biopsies following M11 meeting criteria specified plus all subjects w/biopsies positive for endometrial hyperplasia by any pathologists before M11.

Secondary

MeasureTime frameDescription
Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)Baseline and Week 3Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)Baseline and Week 4Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)Baseline and Week 5Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)Baseline and Week 6Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)Baseline and Week 7Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)Baseline and Week 8Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)Baseline and Week 9Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)Baseline and Week 10Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)Baseline and Week 11Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)Baseline and Week 12Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Severity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)Baseline and Week 1Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)Baseline and Week 2Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)Baseline and Week 3Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)Baseline and Week 4Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)Baseline and Week 5Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)Baseline and Week 6Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)Baseline and Week 7Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)Baseline and Week 8Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)Baseline and Week 9Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)Baseline and Week 10Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)Baseline and Week 11Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)Baseline and Week 12Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)Baseline and Week 1Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)Baseline and Week 2Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)Baseline and Week 3Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)Baseline and Week 4Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)Baseline and Week 5Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)Baseline and Week 6Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)Baseline and Week 7Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)Baseline and Week 8Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)Baseline and Week 9Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)Baseline and Week 10Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)Baseline and Week 11Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)Baseline and Week 12Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)Baseline and Week 1Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)Baseline and Week 2Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)Baseline and Week 3Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)Baseline and Week 4Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)Baseline and Week 5Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)Baseline and Week 6Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)Baseline and Week 7Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)Baseline and Week 8Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)Baseline and Week 9Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)Baseline and Week 10Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)Baseline and Week 11Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)Baseline and Week 12Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)Baseline and Week 1Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe VMS from Baseline to Week 1.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)Baseline and Week 2Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 2.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)Baseline and Week 3Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 3.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)Baseline and Week 4Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)Baseline and Week 5Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 5.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)Baseline and Week 6Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 6.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)Baseline and Week 7Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 7.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)Baseline and Week 8Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)Baseline and Week 9Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 9.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)Baseline and Week 10Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 10.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)Baseline and Week 11Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 11.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)Baseline and Week 5Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 5.
Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)Baseline and Week 12Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)Baseline and Week 1Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 1.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)Baseline and Week 2Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 2.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)Baseline and Week 3Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 3.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)Baseline and Week 4Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 4.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)Baseline and Week 6Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 6.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)Baseline and Week 7Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 7.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)Baseline and Week 8Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 8.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)Baseline and Week 9Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 9.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)Baseline and Week 10Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 10.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)Baseline and Week 11Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 11.
Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)Baseline and Week 12Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 12.
Clinical Global Impression (CGI) - Week 4 (MITT-VMS)Baseline and Week 4The number and percentage of subjects for each possible response to the CGI at Week 4. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)Baseline and Week 4Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4 for the respective CGI category. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
Clinical Global Impression (CGI) - Week 8 (MITT-VMS)Baseline and Week 8The number and percentage of subjects for each possible response to the CGI at Week 8. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)Baseline and Week 8Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8 for the respective CGI category. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
Clinical Global Impression (CGI) - Week 12 (MITT-VMS)Baseline and Week 12The number and percentage of subjects for each possible response to the CGI at Week 12. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)Baseline and Week 12Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12 for the respective CGI category. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
Number of Subjects Without Bleeding for Consecutive CyclesCycle 1 to 13No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
Number of Subjects With Cumulative Amenorrhea From Cycle 1 to 13Cycle 1 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 1 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 2 to 13Cycle 2 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 2 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 3 to 13Cycle 3 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 3 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 4 to 13Cycle 4 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 4 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 5 to 13Cycle 5 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 5 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 6 to 13Cycle 6 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 6 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 7 to 13Cycle 7 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 7 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 8 to 13Cycle 8 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 8 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 9 to 13Cycle 9 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 9 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 10 to 13Cycle 10 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 10 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 11 to 13Cycle 11 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 11 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From Cycle 12 to 13Cycle 12 to 13Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 12 to 13 was calculated and compared between active and placebo treatments.
Number of Subjects With Cumulative Amenorrhea From the 13th CycleThe 13th CycleCumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from the 13th Cycle was calculated and compared between active and placebo treatments.
Subject Incidence With Spotting - Trimester 1 (Safety Pop.)Trimester 1Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Subject Incidence With Spotting - Trimester 2 (Safety Pop.)Trimester 2Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Subject Incidence With Spotting - Trimester 3 (Safety Pop.)Trimester 3Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Subject Incidence With Spotting - Trimester 4 (Safety Pop.)Trimester 4Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Number of Days With Spotting - Trimester 1 (Safety Pop.)Trimester 1Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Number of Days With Spotting - Trimester 2 (Safety Pop.)Trimester 2Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Number of Days With Spotting - Trimester 3 (Safety Pop.)Trimester 3Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Number of Days With Spotting - Trimester 4 (Safety Pop.)Trimester 4Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Subject Incidence With Bleeding - Trimester 1 (Safety Pop.)Trimester 1Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Subject Incidence With Bleeding - Trimester 2 (Safety Pop.)Trimester 2Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Subject Incidence With Bleeding - Trimester 3 (Safety Pop.)Trimester 3Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Subject Incidence With Bleeding - Trimester 4 (Safety Pop.)Trimester 4Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Number of Days With Bleeding - Trimester 1 (Safety Pop.)Trimester 1Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Number of Days With Bleeding - Trimester 2 (Safety Pop.)Trimester 2Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Number of Days With Bleeding - Trimester 3 (Safety Pop.)Trimester 3Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Number of Days With Bleeding - Trimester 4 (Safety Pop.)Trimester 4Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS)Baseline and Week 12Changes in Vasomotor Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS)Baseline and Month 6Changes in Vasomotor Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS)Baseline and Month 12Changes in Vasomotor Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS)Baseline and Week 12Changes in Psychosocial Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS)Baseline and Month 6Changes in Psychosocial Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS)Baseline and Month 12Changes in Psychosocial Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS)Baseline and Week 12Changes in Physical Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS)Baseline and Month 6Changes in Physical Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS)Baseline and Month 12Changes in Physical Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS)Baseline and Week 12Changes in Sexual Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS)Baseline and Month 6Changes in Sexual Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS)Baseline and Month 12Changes in Sexual Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS)Baseline and Week 12Changes in Overall Scores from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS)Baseline and Month 6Changes in Overall Scores from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS)Baseline and Month 12Changes in Overall Scores from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.
Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS)Baseline and Week 12Change from Baseline to Wk 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS)Baseline and Month 6Change from Baseline to Month 6 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS)Baseline and Month 12Change from Baseline to Month 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS)Baseline and Week 12Change from Baseline to Wk 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS)Baseline and Month 6Change from Baseline to Month 6 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS)Baseline and Month 12Change from Baseline to Month 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS)Baseline and Week 12Change from Baseline (BL) to Week 12 in MOS Optimal Sleep Score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.
Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS)Baseline and Month 6Change from Baseline (BL) to Month 6 in MOS Optimal Sleep Score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.
Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS)Baseline and Month 12Change from Baseline (BL) to Month 12 in MOS Optimal Sleep Score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT)Baseline and Week 12Changes in Vasomotor Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT)Baseline and Month 6Changes in Vasomotor Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT)Baseline and Month 12Changes in Vasomotor Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT)Baseline and Week 12Changes in Psychosocial Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT)Baseline and Month 6Changes in Psychosocial Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT)Baseline and Month 12Changes in Psychosocial Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT)Baseline and Week 12Changes in Physical Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT)Baseline and Month 6Changes in Physical Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT)Baseline and Month 12Changes in Physical Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT)Baseline and Week 12Changes in Sexual Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT)Baseline and Month 6Changes in Sexual Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT)Baseline and Month 12Changes in Sexual Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT)Baseline and Week 12Change in Overall Scores from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT)Baseline and Month 6Change in Overall Scores from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.
Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT)Baseline and Month 12Change in Overall Scores from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.
Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT)Baseline and Week 12Change from Baseline to Wk 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT)Baseline and Month 6Change from Baseline to Month 6 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT)Baseline and Month 12Change from Baseline to Month 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
Endometrial Protection - HyperplasiaBaseline and Month 12Endometrial biopsies centrally evaluated by 3 primary pathologists using criteria described in Blaustein's Pathology text. Pathologists classified biopsy into 1 of following 3 categories: Cat.1: Non-endometrial malignancy/non-hyperplasia; Cat.2: Endometrial hyperplasia; Cat.3: Endometrial malignancy. Consensus was reached when the 2 of 3 pathologist readers agreed on any of the above categories; if all three reads were disparate, the final diagnosis was based on the most severe diagnosis. Incidence rate calculated as: I=A/B where I=incidence rate at M12 evaluation, A=all new subjects with biopsies positive for endometrial hyperplasia during study but post-Baseline, B=all subjects with biopsies following M11 meeting the criteria specified plus all subjects with biopsies positive for endometrial hyperplasia by any of the pathologists before M11.
Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT)Baseline and Week 12Change from Baseline to Wk 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT)Baseline and Month 6Change from Baseline to Month 6 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT)Baseline and Month 12Change from Baseline to Month 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT)Baseline and Week 12Change from Baseline to Wk 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT)Baseline and Month 6Change from Baseline to Month 6 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT)Baseline and Week 12Change from Baseline (BL) to Wk 12 in MOS Optimal Sleep Score as compared with Placebo.The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.
Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT)Baseline and Month 6Change from Baseline (BL) to Month 6 in MOS Optimal Sleep Score as compared with Placebo.The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.
Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT)Baseline and Month 12Change from Baseline (BL) to Month 12 in MOS Optimal Sleep Score as compared with Placebo.The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.
Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT)Baseline and Month 12Change from Baseline to Month 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)Baseline and Week 1Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)Baseline and Week 2Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Countries

United States

Participant flow

Participants by arm

ArmCount
Combined Estradiol 1 mg / Progesterone 100 mg
Combined Estradiol 1 mg / Progesterone 100 mg formulation and placebo softgel capsules taken orally once a day for twelve months.
415
Combined Estradiol 0.5 mg / Progesterone 100 mg
Combined Estradiol 0.5 mg / Progesterone 100 mg formulation and placebo softgel capsules taken orally once a day for twelve months.
424
Combined Estradiol 0.5 mg / Progesterone 50 mg
Combined Estradiol 0.5 mg / Progesterone 50 mg formulation and placebo softgel capsules taken orally once a day for twelve months.
421
Combined Estradiol 0.25 mg / Progesterone 50 mg
Combined Estradiol 0.25 mg / Progesterone 50 mg formulation and placebo softgel capsules taken orally once a day for twelve months.
424
Placebo
Two Placebo softgel capsules taken orally once a day for twelve months.
151
Total1,835

Baseline characteristics

CharacteristicCombined Estradiol 0.5 mg / Progesterone 100 mgCombined Estradiol 0.5 mg / Progesterone 50 mgCombined Estradiol 0.25 mg / Progesterone 50 mgCombined Estradiol 1 mg / Progesterone 100 mgPlaceboTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
424 Participants421 Participants424 Participants415 Participants151 Participants1835 Participants
Age, Continuous54.5 years
STANDARD_DEVIATION 4.52
54.9 years
STANDARD_DEVIATION 4.27
54.4 years
STANDARD_DEVIATION 4.04
54.7 years
STANDARD_DEVIATION 4.37
54.5 years
STANDARD_DEVIATION 4.32
54.6 years
STANDARD_DEVIATION 4.31
Region of Enrollment
United States
424 participants421 participants424 participants415 participants151 participants1835 participants
Sex: Female, Male
Female
424 Participants421 Participants424 Participants415 Participants151 Participants1835 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
deaths
Total, all-cause mortality
0 / 4150 / 4241 / 4210 / 4240 / 151
other
Total, other adverse events
324 / 415277 / 424291 / 421232 / 42441 / 151
serious
Total, serious adverse events
9 / 41515 / 4249 / 42111 / 4242 / 151

Outcome results

Primary

Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-55.1 weekly hot flushesStandard Deviation 31.36
Combined Estradiol 0.5 mg / Progesterone 100 mgCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-53.7 weekly hot flushesStandard Deviation 31.93
Combined Estradiol 0.5 mg / Progesterone 50 mgCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-50.2 weekly hot flushesStandard Deviation 31.35
Combined Estradiol 0.25 mg / Progesterone 50 mgCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-52.4 weekly hot flushesStandard Deviation 33.9
PlaceboCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-40.2 weekly hot flushesStandard Deviation 29.79
p-value: <0.00195% CI: [-23.33, -9.82]Mixed Models Analysis
p-value: <0.00195% CI: [-21.72, -8.42]Mixed Models Analysis
p-value: 0.00295% CI: [-17.48, -4.1]Mixed Models Analysis
p-value: <0.00195% CI: [-18.31, -5.11]Mixed Models Analysis
Primary

Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-40.6 weekly hot flushesStandard Deviation 30.59
Combined Estradiol 0.5 mg / Progesterone 100 mgCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-35.1 weekly hot flushesStandard Deviation 29.14
Combined Estradiol 0.5 mg / Progesterone 50 mgCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-33.6 weekly hot flushesStandard Deviation 30.64
Combined Estradiol 0.25 mg / Progesterone 50 mgCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-38.9 weekly hot flushesStandard Deviation 31.04
PlaceboCo-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-26.4 weekly hot flushesStandard Deviation 27.05
p-value: <0.00195% CI: [-19.29, -6.32]Mixed Models Analysis
p-value: 0.01395% CI: [-14.46, -1.68]Mixed Models Analysis
p-value: 0.14195% CI: [-11.21, 1.59]Mixed Models Analysis
p-value: 0.00195% CI: [-16.73, -4.08]Mixed Models Analysis
Primary

Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-1.12 scores on a scaleStandard Deviation 0.963
Combined Estradiol 0.5 mg / Progesterone 100 mgCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-0.90 scores on a scaleStandard Deviation 0.783
Combined Estradiol 0.5 mg / Progesterone 50 mgCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-0.76 scores on a scaleStandard Deviation 0.744
Combined Estradiol 0.25 mg / Progesterone 50 mgCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-0.71 scores on a scaleStandard Deviation 0.806
PlaceboCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-0.56 scores on a scaleStandard Deviation 0.603
p-value: <0.00195% CI: [-0.77, -0.38]Mixed Models Analysis
p-value: <0.00195% CI: [-0.59, -0.2]Mixed Models Analysis
p-value: 0.01895% CI: [-0.43, -0.04]Mixed Models Analysis
p-value: 0.09695% CI: [-0.36, 0.03]Mixed Models Analysis
Primary

Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-0.48 scores on a scaleStandard Deviation 0.547
Combined Estradiol 0.5 mg / Progesterone 100 mgCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-0.51 scores on a scaleStandard Deviation 0.563
Combined Estradiol 0.5 mg / Progesterone 50 mgCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-0.40 scores on a scaleStandard Deviation 0.469
Combined Estradiol 0.25 mg / Progesterone 50 mgCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-0.44 scores on a scaleStandard Deviation 0.514
PlaceboCo-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)-0.34 scores on a scaleStandard Deviation 0.386
p-value: 0.03195% CI: [-0.25, -0.01]Mixed Models Analysis
p-value: 0.00595% CI: [-0.28, -0.05]Mixed Models Analysis
p-value: 0.40195% CI: [-0.17, 0.07]Mixed Models Analysis
p-value: 0.195% CI: [-0.21, 0.02]Mixed Models Analysis
Primary

Primary Safety Endpoint: Endometrial Protection - Hyperplasia

Endometrial biopsies centrally evaluated by 2 primary pathologists using criteria from Blaustein's Pathology text. Pathologists classified bx into 1 of following 3 categories: Cat.1: Non-endometrial malignancy/non-hyperplasia; Cat.2: Endometrial hyperplasia; Cat.3: Endometrial malignancy. Consensus reached when 2 primary pathologist agreed on any of above categories; if primary pathologists disagreed on presence of hyperplasia, result of 3rd pathologist was utilized and final decision regarding presence of hyperplasia was based on diagnosis of majority. If all 3 reads disparate, final diagnosis based on most severe dx. Incidence rate calculated as: I=A/B where I=incidence rate at M12 evaluation, A=all new subjects with biopsies positive for endometrial hyperplasia during study but post-Baseline, B=all subjects w/biopsies following M11 meeting criteria specified plus all subjects w/biopsies positive for endometrial hyperplasia by any pathologists before M11.

Time frame: Baseline and Month 12

Population: Randomized subjects who had taken at least 1 capsule, had no major protocol violations, acceptable biopsy at baseline (evaluable tissue, no endometrial hyperplasia, polyp or cancer), had a biopsy at month 12 (on or after Study Day 326) or had a diagnosis of endometrial hyperplasia prior to month 12.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgPrimary Safety Endpoint: Endometrial Protection - Hyperplasia0 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgPrimary Safety Endpoint: Endometrial Protection - Hyperplasia0 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgPrimary Safety Endpoint: Endometrial Protection - Hyperplasia0 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgPrimary Safety Endpoint: Endometrial Protection - Hyperplasia0 Participants
PlaceboPrimary Safety Endpoint: Endometrial Protection - Hyperplasia0 Participants
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Combined Estradiol 1 mg / Progesterone 100 mg.
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Combined Estradiol 0.5 mg / Progesterone 100 mg.
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Combined Estradiol 0.5 mg / Progesterone 50 mg.
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Combined Estradiol 0.25 mg / Progesterone 50 mg.
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Placebo.
Secondary

Clinical Global Impression (CGI) - Week 12 (MITT-VMS)

The number and percentage of subjects for each possible response to the CGI at Week 12. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)(Very) Much Improved101 Participants
Combined Estradiol 1 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)No Change or Worse5 Participants
Combined Estradiol 1 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)Minimally Improved17 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)Minimally Improved29 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)(Very) Much Improved97 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)No Change or Worse7 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)Minimally Improved22 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)(Very) Much Improved102 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)No Change or Worse7 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)(Very) Much Improved101 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)No Change or Worse14 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 12 (MITT-VMS)Minimally Improved24 Participants
PlaceboClinical Global Impression (CGI) - Week 12 (MITT-VMS)Minimally Improved26 Participants
PlaceboClinical Global Impression (CGI) - Week 12 (MITT-VMS)(Very) Much Improved62 Participants
PlaceboClinical Global Impression (CGI) - Week 12 (MITT-VMS)No Change or Worse28 Participants
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.002Fisher Exact
Secondary

Clinical Global Impression (CGI) - Week 4 (MITT-VMS)

The number and percentage of subjects for each possible response to the CGI at Week 4. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)(Very) Much Improved86 Participants
Combined Estradiol 1 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)No Change or Worse13 Participants
Combined Estradiol 1 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)Minimally Improved37 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)Minimally Improved49 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)(Very) Much Improved71 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)No Change or Worse21 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)Minimally Improved49 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)(Very) Much Improved72 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)No Change or Worse23 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)(Very) Much Improved75 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)No Change or Worse22 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 4 (MITT-VMS)Minimally Improved51 Participants
PlaceboClinical Global Impression (CGI) - Week 4 (MITT-VMS)Minimally Improved49 Participants
PlaceboClinical Global Impression (CGI) - Week 4 (MITT-VMS)(Very) Much Improved41 Participants
PlaceboClinical Global Impression (CGI) - Week 4 (MITT-VMS)No Change or Worse35 Participants
p-value: <0.001Fisher Exact
p-value: 0.005Fisher Exact
p-value: 0.007Fisher Exact
p-value: 0.004Fisher Exact
Secondary

Clinical Global Impression (CGI) - Week 8 (MITT-VMS)

The number and percentage of subjects for each possible response to the CGI at Week 8. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.

Time frame: Baseline and Week 8

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)Minimally Improved23 Participants
Combined Estradiol 1 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)(Very) Much Improved101 Participants
Combined Estradiol 1 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)No Change or Worse6 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)Minimally Improved24 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)(Very) Much Improved103 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)No Change or Worse12 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)Minimally Improved23 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)(Very) Much Improved98 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)No Change or Worse13 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)(Very) Much Improved93 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)No Change or Worse13 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgClinical Global Impression (CGI) - Week 8 (MITT-VMS)Minimally Improved35 Participants
PlaceboClinical Global Impression (CGI) - Week 8 (MITT-VMS)Minimally Improved25 Participants
PlaceboClinical Global Impression (CGI) - Week 8 (MITT-VMS)(Very) Much Improved62 Participants
PlaceboClinical Global Impression (CGI) - Week 8 (MITT-VMS)No Change or Worse30 Participants
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.001Fisher Exact
p-value: 0.002Fisher Exact
Secondary

Endometrial Protection - Hyperplasia

Endometrial biopsies centrally evaluated by 3 primary pathologists using criteria described in Blaustein's Pathology text. Pathologists classified biopsy into 1 of following 3 categories: Cat.1: Non-endometrial malignancy/non-hyperplasia; Cat.2: Endometrial hyperplasia; Cat.3: Endometrial malignancy. Consensus was reached when the 2 of 3 pathologist readers agreed on any of the above categories; if all three reads were disparate, the final diagnosis was based on the most severe diagnosis. Incidence rate calculated as: I=A/B where I=incidence rate at M12 evaluation, A=all new subjects with biopsies positive for endometrial hyperplasia during study but post-Baseline, B=all subjects with biopsies following M11 meeting the criteria specified plus all subjects with biopsies positive for endometrial hyperplasia by any of the pathologists before M11.

Time frame: Baseline and Month 12

Population: Randomized subjects who had taken at least 1 capsule, had no major protocol violations, acceptable biopsy at baseline (evaluable tissue, no endometrial hyperplasia, polyp or cancer), had a biopsy at month 12 (on or after Study Day 326) or had a diagnosis of endometrial hyperplasia prior to month 12.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgEndometrial Protection - Hyperplasia0 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgEndometrial Protection - Hyperplasia0 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgEndometrial Protection - Hyperplasia0 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgEndometrial Protection - Hyperplasia0 Participants
PlaceboEndometrial Protection - Hyperplasia0 Participants
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Combined Estradiol 1 mg / Progesterone 100 mg.
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Combined Estradiol 0.5 mg / Progesterone 100 mg.
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Combined Estradiol 0.5 mg / Progesterone 50 mg.
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Combined Estradiol 0.25 mg / Progesterone 50 mg.
Comparison: Between group comparison is not intended. The purpose of the analysis is to calculate the incidence rate and the 95% CI of endometrial hyperplasia per FDA published guidance for Placebo.
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 10

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-58.5 weekly hot flushesStandard Deviation 36.86
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-56.1 weekly hot flushesStandard Deviation 39.97
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-53.7 weekly hot flushesStandard Deviation 34.39
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-55.7 weekly hot flushesStandard Deviation 41.55
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-38.3 weekly hot flushesStandard Deviation 35.52
p-value: <0.00195% CI: [-28.72, -13.29]Mixed Models Analysis
p-value: <0.00195% CI: [-25.96, -10.78]Mixed Models Analysis
p-value: <0.00195% CI: [-20.66, -5.39]Mixed Models Analysis
p-value: <0.00195% CI: [-22.19, -7.12]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 11

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-58.8 weekly hot flushesStandard Deviation 36.58
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-57.0 weekly hot flushesStandard Deviation 38.81
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-54.2 weekly hot flushesStandard Deviation 34.38
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-56.1 weekly hot flushesStandard Deviation 42.45
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-38.4 weekly hot flushesStandard Deviation 35.85
p-value: <0.00195% CI: [-29.57, -14.08]Mixed Models Analysis
p-value: <0.00195% CI: [-27.02, -11.77]Mixed Models Analysis
p-value: <0.00195% CI: [-21.65, -6.32]Mixed Models Analysis
p-value: <0.00195% CI: [-23.23, -8.1]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-60.3 weekly hot flushesStandard Deviation 36.42
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-58.8 weekly hot flushesStandard Deviation 39.59
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-54.8 weekly hot flushesStandard Deviation 34.94
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-57.0 weekly hot flushesStandard Deviation 41.71
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-41.7 weekly hot flushesStandard Deviation 36.35
p-value: <0.00195% CI: [-28.32, -12.89]Mixed Models Analysis
p-value: <0.00195% CI: [-25.84, -10.65]Mixed Models Analysis
p-value: 0.00195% CI: [-20.26, -4.98]Mixed Models Analysis
p-value: <0.00195% CI: [-21.51, -6.43]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 1

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-12.9 weekly hot flushesStandard Deviation 22.12
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-12.4 weekly hot flushesStandard Deviation 23.94
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-12.5 weekly hot flushesStandard Deviation 24.62
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-17.7 weekly hot flushesStandard Deviation 27.78
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-12.2 weekly hot flushesStandard Deviation 23.76
p-value: 0.86595% CI: [-5.16, 6.14]Mixed Models Analysis
p-value: 0.84795% CI: [-5.01, 6.1]Mixed Models Analysis
p-value: 0.46395% CI: [-3.5, 7.68]Mixed Models Analysis
p-value: 0.20795% CI: [-9.07, 1.97]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 2

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-28.2 weekly hot flushesStandard Deviation 29.45
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-22.4 weekly hot flushesStandard Deviation 30.53
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-21.8 weekly hot flushesStandard Deviation 31.66
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-27.8 weekly hot flushesStandard Deviation 32.35
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-21.7 weekly hot flushesStandard Deviation 27.45
p-value: 0.1495% CI: [-11.8, 1.67]Mixed Models Analysis
p-value: 0.98295% CI: [-6.7, 6.55]Mixed Models Analysis
p-value: 0.49295% CI: [-4.32, 8.98]Mixed Models Analysis
p-value: 0.21695% CI: [-10.72, 2.43]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 3

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-37.4 weekly hot flushesStandard Deviation 32.33
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-30.7 weekly hot flushesStandard Deviation 32
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-31.3 weekly hot flushesStandard Deviation 30.79
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-35.6 weekly hot flushesStandard Deviation 33.52
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-25.8 weekly hot flushesStandard Deviation 30.41
p-value: 0.00395% CI: [-17.26, -3.5]Mixed Models Analysis
p-value: 0.27795% CI: [-10.53, 3.02]Mixed Models Analysis
p-value: 0.39495% CI: [-9.75, 3.84]Mixed Models Analysis
p-value: 0.02295% CI: [-14.58, -1.15]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-44.4 weekly hot flushesStandard Deviation 34.53
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-37.7 weekly hot flushesStandard Deviation 35.38
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-35.4 weekly hot flushesStandard Deviation 34.58
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-41.5 weekly hot flushesStandard Deviation 37.4
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-26.8 weekly hot flushesStandard Deviation 30.52
p-value: <0.00195% CI: [-22.75, -7.89]Mixed Models Analysis
p-value: 0.01795% CI: [-16.24, -1.6]Mixed Models Analysis
p-value: 0.22395% CI: [-11.9, 2.78]Mixed Models Analysis
p-value: 0.00295% CI: [-18.57, -4.07]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 5

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-49.9 weekly hot flushesStandard Deviation 33.86
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-42.3 weekly hot flushesStandard Deviation 34.15
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-40.1 weekly hot flushesStandard Deviation 32.52
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-46.8 weekly hot flushesStandard Deviation 39.88
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-33.3 weekly hot flushesStandard Deviation 33.49
p-value: <0.00195% CI: [-24.65, -10.28]Mixed Models Analysis
p-value: 0.00595% CI: [-17.33, -3.18]Mixed Models Analysis
p-value: 0.08795% CI: [-13.31, 0.89]Mixed Models Analysis
p-value: <0.00195% CI: [-19.68, -5.65]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-53.9 weekly hot flushesStandard Deviation 35.34
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-44.9 weekly hot flushesStandard Deviation 36.12
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-43.0 weekly hot flushesStandard Deviation 34.84
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-49.4 weekly hot flushesStandard Deviation 40.28
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-34.1 weekly hot flushesStandard Deviation 33.32
p-value: <0.00195% CI: [-27.77, -12.87]Mixed Models Analysis
p-value: <0.00195% CI: [-19.95, -5.28]Mixed Models Analysis
p-value: 0.02795% CI: [-15.7, -0.96]Mixed Models Analysis
p-value: <0.00195% CI: [-21.13, -6.58]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 7

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-56.1 weekly hot flushesStandard Deviation 34.55
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-48.8 weekly hot flushesStandard Deviation 36.92
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-47.2 weekly hot flushesStandard Deviation 34.39
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-51.5 weekly hot flushesStandard Deviation 39.69
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-33.4 weekly hot flushesStandard Deviation 33.71
p-value: <0.00195% CI: [-22.97, -8.49]Mixed Models Analysis
p-value: <0.00195% CI: [-28.87, -14.04]Mixed Models Analysis
p-value: <0.00195% CI: [-23.39, -8.8]Mixed Models Analysis
p-value: 0.00195% CI: [-19.34, -4.68]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 8

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-57.1 weekly hot flushesStandard Deviation 35.91
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-50.6 weekly hot flushesStandard Deviation 37.73
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-49.5 weekly hot flushesStandard Deviation 34.34
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-52.4 weekly hot flushesStandard Deviation 40.65
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-36.9 weekly hot flushesStandard Deviation 35.53
p-value: <0.00195% CI: [-28.06, -12.97]Mixed Models Analysis
p-value: <0.00195% CI: [-22.8, -7.95]Mixed Models Analysis
p-value: 0.00395% CI: [-18.95, -4.03]Mixed Models Analysis
p-value: <0.00195% CI: [-21.19, -6.46]Mixed Models Analysis
Secondary

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.

Time frame: Baseline and Week 9

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-57.6 weekly hot flushesStandard Deviation 36.43
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-54.7 weekly hot flushesStandard Deviation 38.76
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-52.8 weekly hot flushesStandard Deviation 33.68
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-54.5 weekly hot flushesStandard Deviation 41.89
PlaceboFrequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-38.3 weekly hot flushesStandard Deviation 35.04
p-value: <0.00195% CI: [-27.93, -12.74]Mixed Models Analysis
p-value: <0.00195% CI: [-25.39, -10.45]Mixed Models Analysis
p-value: <0.00195% CI: [-20.49, -5.46]Mixed Models Analysis
p-value: <0.00195% CI: [-21.7, -6.87]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 10

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-53.2 weekly hot flushesStandard Deviation 32.58
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-51.9 weekly hot flushesStandard Deviation 32.79
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-49.0 weekly hot flushesStandard Deviation 30.24
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-50.6 weekly hot flushesStandard Deviation 33.36
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-37.1 weekly hot flushesStandard Deviation 29.74
p-value: <0.00195% CI: [-23.58, -10.03]Mixed Models Analysis
p-value: <0.00195% CI: [-22.32, -8.99]Mixed Models Analysis
p-value: 0.00195% CI: [-17.9, -4.49]Mixed Models Analysis
p-value: <0.00195% CI: [-18.78, -5.55]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 11

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-53.7 weekly hot flushesStandard Deviation 32.21
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-52.0 weekly hot flushesStandard Deviation 31.24
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-49.4 weekly hot flushesStandard Deviation 30.71
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-50.9 weekly hot flushesStandard Deviation 34.33
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-36.7 weekly hot flushesStandard Deviation 30.32
p-value: <0.00195% CI: [-24.92, -11.29]Mixed Models Analysis
p-value: <0.00195% CI: [-23.17, -9.74]Mixed Models Analysis
p-value: <0.00195% CI: [-19.15, -5.66]Mixed Models Analysis
p-value: <0.00195% CI: [-20.26, -6.93]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-55.1 weekly hot flushesStandard Deviation 31.36
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-53.7 weekly hot flushesStandard Deviation 31.93
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-50.2 weekly hot flushesStandard Deviation 31.35
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-52.4 weekly hot flushesStandard Deviation 33.9
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-40.2 weekly hot flushesStandard Deviation 29.79
p-value: <0.00195% CI: [-23.33, -9.82]Mixed Models Analysis
p-value: <0.00195% CI: [-21.72, -8.42]Mixed Models Analysis
p-value: 0.00295% CI: [-17.48, -4.1]Mixed Models Analysis
p-value: <0.00195% CI: [-18.31, -5.11]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 1

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-12.2 weekly hot flushesStandard Deviation 20.1
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-11.5 weekly hot flushesStandard Deviation 20.19
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-11.0 weekly hot flushesStandard Deviation 20.94
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-16.3 weekly hot flushesStandard Deviation 22.28
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-13.0 weekly hot flushesStandard Deviation 21.25
p-value: 0.58895% CI: [-3.57, 6.3]Mixed Models Analysis
p-value: 0.60195% CI: [-3.56, 6.15]Mixed Models Analysis
p-value: 0.20295% CI: [-1.71, 8.06]Mixed Models Analysis
p-value: 0.43195% CI: [-6.76, 2.89]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 2

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-26.6 weekly hot flushesStandard Deviation 27.67
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-21.2 weekly hot flushesStandard Deviation 24.79
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-19.0 weekly hot flushesStandard Deviation 28.32
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-25.4 weekly hot flushesStandard Deviation 26.63
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-21.3 weekly hot flushesStandard Deviation 24.75
p-value: 0.15495% CI: [-10.34, 1.64]Mixed Models Analysis
p-value: 0.95695% CI: [-6.06, 5.73]Mixed Models Analysis
p-value: 0.2495% CI: [-2.37, 9.46]Mixed Models Analysis
p-value: 0.35395% CI: [-8.62, 3.08]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 3

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-34.3 weekly hot flushesStandard Deviation 29.22
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-29.0 weekly hot flushesStandard Deviation 26.73
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-28.1 weekly hot flushesStandard Deviation 28.18
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-33.6 weekly hot flushesStandard Deviation 27.76
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-25.1 weekly hot flushesStandard Deviation 27.26
p-value: 0.00795% CI: [-14.75, -2.36]Mixed Models Analysis
p-value: 0.22795% CI: [-9.86, 2.35]Mixed Models Analysis
p-value: 0.59795% CI: [-7.77, 4.47]Mixed Models Analysis
p-value: 0.01995% CI: [-13.28, -1.19]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-40.6 weekly hot flushesStandard Deviation 30.59
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-35.1 weekly hot flushesStandard Deviation 29.14
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-33.6 weekly hot flushesStandard Deviation 30.64
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-38.9 weekly hot flushesStandard Deviation 31.04
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-26.4 weekly hot flushesStandard Deviation 27.05
p-value: <0.00195% CI: [-19.29, -6.32]Mixed Models Analysis
p-value: 0.01395% CI: [-14.46, -1.68]Mixed Models Analysis
p-value: 0.14195% CI: [-11.21, 1.59]Mixed Models Analysis
p-value: 0.00195% CI: [-16.73, -4.08]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 5

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-45.9 weekly hot flushesStandard Deviation 32.31
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-39.5 weekly hot flushesStandard Deviation 28.53
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-37.1 weekly hot flushesStandard Deviation 30.64
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-43.5 weekly hot flushesStandard Deviation 33.31
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-31.6 weekly hot flushesStandard Deviation 28.96
p-value: <0.00195% CI: [-22.16, -9.02]Mixed Models Analysis
p-value: 0.00395% CI: [-16.34, -3.41]Mixed Models Analysis
p-value: 0.07595% CI: [-12.4, 0.59]Mixed Models Analysis
p-value: <0.00195% CI: [-18.47, -5.64]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-49.4 weekly hot flushesStandard Deviation 32.76
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-41.7 weekly hot flushesStandard Deviation 29.97
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-40.1 weekly hot flushesStandard Deviation 33.62
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-45.5 weekly hot flushesStandard Deviation 33.14
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-32.7 weekly hot flushesStandard Deviation 28.53
p-value: <0.00195% CI: [-24.57, -11.05]Mixed Models Analysis
p-value: <0.00195% CI: [-18, -4.7]Mixed Models Analysis
p-value: 0.02295% CI: [-14.5, -1.14]Mixed Models Analysis
p-value: <0.00195% CI: [-19.11, -5.91]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 7

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-51.5 weekly hot flushesStandard Deviation 31.51
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-45.0 weekly hot flushesStandard Deviation 30.73
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-43.8 weekly hot flushesStandard Deviation 33.2
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-47.7 weekly hot flushesStandard Deviation 32.18
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-33.4 weekly hot flushesStandard Deviation 29.37
p-value: <0.00195% CI: [-24.45, -11.06]Mixed Models Analysis
p-value: <0.00195% CI: [-19.88, -6.7]Mixed Models Analysis
p-value: 0.00395% CI: [-16.83, -3.6]Mixed Models Analysis
p-value: <0.00195% CI: [-20.15, -7.07]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 8

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-52.3 weekly hot flushesStandard Deviation 31.63
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-46.8 weekly hot flushesStandard Deviation 30.64
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-45.4 weekly hot flushesStandard Deviation 32.55
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-48.4 weekly hot flushesStandard Deviation 32.82
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-36.0 weekly hot flushesStandard Deviation 30.66
p-value: <0.00195% CI: [-23.35, -9.91]Mixed Models Analysis
p-value: <0.00195% CI: [-19.58, -6.36]Mixed Models Analysis
p-value: 0.00595% CI: [-16.27, -2.99]Mixed Models Analysis
p-value: <0.00195% CI: [-18.53, -5.41]Mixed Models Analysis
Secondary

Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.

Time frame: Baseline and Week 9

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-52.6 weekly hot flushesStandard Deviation 32.57
Combined Estradiol 0.5 mg / Progesterone 100 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-50.5 weekly hot flushesStandard Deviation 31.01
Combined Estradiol 0.5 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-47.4 weekly hot flushesStandard Deviation 30.13
Combined Estradiol 0.25 mg / Progesterone 50 mgFrequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-50.1 weekly hot flushesStandard Deviation 33.92
PlaceboFrequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-36.4 weekly hot flushesStandard Deviation 29.09
p-value: <0.00195% CI: [-23.79, -10.44]Mixed Models Analysis
p-value: <0.00195% CI: [-22.15, -9.01]Mixed Models Analysis
p-value: 0.00195% CI: [-17.65, -4.44]Mixed Models Analysis
p-value: <0.00195% CI: [-19.54, -6.5]Mixed Models Analysis
Secondary

Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12 for the respective CGI category. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)(Very) Much Improved-58.8 weekly hot flushesStandard Deviation 30.71
Combined Estradiol 1 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)No Change or Worse-30.7 weekly hot flushesStandard Deviation 32.89
Combined Estradiol 1 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)Minimally Improved-35.9 weekly hot flushesStandard Deviation 24.78
Combined Estradiol 0.5 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)Minimally Improved-34.9 weekly hot flushesStandard Deviation 40.36
Combined Estradiol 0.5 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)(Very) Much Improved-60.0 weekly hot flushesStandard Deviation 28.37
Combined Estradiol 0.5 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)No Change or Worse-38.8 weekly hot flushesStandard Deviation 18.99
Combined Estradiol 0.5 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)Minimally Improved-28.8 weekly hot flushesStandard Deviation 21.99
Combined Estradiol 0.5 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)(Very) Much Improved-58.2 weekly hot flushesStandard Deviation 29.42
Combined Estradiol 0.5 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)No Change or Worse-8.6 weekly hot flushesStandard Deviation 18.42
Combined Estradiol 0.25 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)(Very) Much Improved-59.9 weekly hot flushesStandard Deviation 28.01
Combined Estradiol 0.25 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)No Change or Worse-8.3 weekly hot flushesStandard Deviation 31.84
Combined Estradiol 0.25 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)Minimally Improved-40.6 weekly hot flushesStandard Deviation 37.36
PlaceboMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)Minimally Improved-35.7 weekly hot flushesStandard Deviation 19.55
PlaceboMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)(Very) Much Improved-56.2 weekly hot flushesStandard Deviation 26.5
PlaceboMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)No Change or Worse-9.2 weekly hot flushesStandard Deviation 16.77
Secondary

Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4 for the respective CGI category. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)(Very) Much Improved-52.5 weekly hot flushesStandard Deviation 27.28
Combined Estradiol 1 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)No Change or Worse-6.5 weekly hot flushesStandard Deviation 23.08
Combined Estradiol 1 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)Minimally Improved-24.1 weekly hot flushesStandard Deviation 23.87
Combined Estradiol 0.5 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)Minimally Improved-25.9 weekly hot flushesStandard Deviation 21.43
Combined Estradiol 0.5 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)(Very) Much Improved-48.6 weekly hot flushesStandard Deviation 28.87
Combined Estradiol 0.5 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)No Change or Worse-6.6 weekly hot flushesStandard Deviation 16.39
Combined Estradiol 0.5 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)Minimally Improved-29.2 weekly hot flushesStandard Deviation 23.26
Combined Estradiol 0.5 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)(Very) Much Improved-46.2 weekly hot flushesStandard Deviation 31.23
Combined Estradiol 0.5 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)No Change or Worse-2.7 weekly hot flushesStandard Deviation 16.22
Combined Estradiol 0.25 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)(Very) Much Improved-55.7 weekly hot flushesStandard Deviation 25.69
Combined Estradiol 0.25 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)No Change or Worse-5.3 weekly hot flushesStandard Deviation 21.97
Combined Estradiol 0.25 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)Minimally Improved-28.9 weekly hot flushesStandard Deviation 26.08
PlaceboMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)Minimally Improved-26.8 weekly hot flushesStandard Deviation 17.68
PlaceboMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)(Very) Much Improved-47.0 weekly hot flushesStandard Deviation 24.17
PlaceboMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)No Change or Worse-5.3 weekly hot flushesStandard Deviation 13.68
Secondary

Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)

Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8 for the respective CGI category. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.

Time frame: Baseline and Week 8

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)(Very) Much Improved-60.8 weekly hot flushesStandard Deviation 28.49
Combined Estradiol 1 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)No Change or Worse-0.2 weekly hot flushesStandard Deviation 28.8
Combined Estradiol 1 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)Minimally Improved-28.7 weekly hot flushesStandard Deviation 18.93
Combined Estradiol 0.5 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)Minimally Improved-27.3 weekly hot flushesStandard Deviation 25.22
Combined Estradiol 0.5 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)(Very) Much Improved-55.1 weekly hot flushesStandard Deviation 29.27
Combined Estradiol 0.5 mg / Progesterone 100 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)No Change or Worse-15.2 weekly hot flushesStandard Deviation 13.41
Combined Estradiol 0.5 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)(Very) Much Improved-55.4 weekly hot flushesStandard Deviation 29.06
Combined Estradiol 0.5 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)Minimally Improved-27.2 weekly hot flushesStandard Deviation 22.79
Combined Estradiol 0.5 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)No Change or Worse-1.6 weekly hot flushesStandard Deviation 19.93
Combined Estradiol 0.25 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)(Very) Much Improved-57.8 weekly hot flushesStandard Deviation 30.38
Combined Estradiol 0.25 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)No Change or Worse-7.4 weekly hot flushesStandard Deviation 21.48
Combined Estradiol 0.25 mg / Progesterone 50 mgMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)Minimally Improved-36.8 weekly hot flushesStandard Deviation 24.81
PlaceboMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)Minimally Improved-27.0 weekly hot flushesStandard Deviation 13.54
PlaceboMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)(Very) Much Improved-52.6 weekly hot flushesStandard Deviation 24.62
PlaceboMean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)No Change or Worse-7.1 weekly hot flushesStandard Deviation 21.46
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT)

Change from Baseline to Month 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT)9.8 score on a scaleStandard Deviation 27.33
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT)12.0 score on a scaleStandard Deviation 29.86
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT)12.6 score on a scaleStandard Deviation 27.71
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT)14.1 score on a scaleStandard Deviation 28.81
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT)10.0 score on a scaleStandard Deviation 31.76
p-value: 0.08995% CI: [-0.76, 10.8]Mixed Models Analysis
p-value: 0.0195% CI: [1.83, 13.29]Mixed Models Analysis
p-value: 0.00995% CI: [1.94, 13.36]Mixed Models Analysis
p-value: 0.00795% CI: [2.11, 13.67]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS)

Change from Baseline to Month 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS)10.4 score on a scaleStandard Deviation 28.43
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS)10.5 score on a scaleStandard Deviation 31.07
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS)17.6 score on a scaleStandard Deviation 31.61
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS)13.7 score on a scaleStandard Deviation 27.7
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS)10.0 score on a scaleStandard Deviation 31.76
p-value: 0.79695% CI: [-6.34, 8.27]Mixed Models Analysis
p-value: 0.1595% CI: [-1.87, 12.15]Mixed Models Analysis
p-value: 0.01995% CI: [1.39, 15.77]Mixed Models Analysis
p-value: 0.04195% CI: [0.3, 14.71]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT)

Change from Baseline to Month 6 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT)10.5 score on a scaleStandard Deviation 26.86
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT)11.7 score on a scaleStandard Deviation 28.11
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT)11.0 score on a scaleStandard Deviation 28.85
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT)14.5 score on a scaleStandard Deviation 27.92
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT)9.5 score on a scaleStandard Deviation 27.36
p-value: 0.05495% CI: [-0.08, 10.31]Mixed Models Analysis
p-value: 0.00795% CI: [1.93, 12.26]Mixed Models Analysis
p-value: 0.02595% CI: [0.75, 11.04]Mixed Models Analysis
p-value: 0.00295% CI: [3.2, 13.55]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS)

Change from Baseline to Month 6 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS)13.2 score on a scaleStandard Deviation 28.61
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS)15.2 score on a scaleStandard Deviation 26.89
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS)14.7 score on a scaleStandard Deviation 30.12
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS)15.2 score on a scaleStandard Deviation 28.75
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS)9.5 score on a scaleStandard Deviation 27.36
p-value: 0.20595% CI: [-2.23, 10.37]Mixed Models Analysis
p-value: 0.00295% CI: [3.43, 15.74]Mixed Models Analysis
p-value: 0.11595% CI: [-1.23, 11.32]Mixed Models Analysis
p-value: 0.00595% CI: [2.75, 15.13]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT)

Change from Baseline to Wk 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT)11.9 score on a scaleStandard Deviation 29.12
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT)9.0 score on a scaleStandard Deviation 27.4
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT)11.4 score on a scaleStandard Deviation 27.54
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT)11.9 score on a scaleStandard Deviation 27.3
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT)11.3 score on a scaleStandard Deviation 25.98
p-value: 0.08495% CI: [-0.58, 9.28]Mixed Models Analysis
p-value: 0.29895% CI: [-2.3, 7.53]Mixed Models Analysis
p-value: 0.13695% CI: [-1.17, 8.62]Mixed Models Analysis
p-value: 0.16395% CI: [-1.41, 8.37]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS)

Change from Baseline to Wk 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS\_4\_new = (6-MOS\_4\_old) x 20; MOS\_12\_new = (6-MOS\_12\_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS)12.8 score on a scaleStandard Deviation 28.3
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS)11.0 score on a scaleStandard Deviation 26.57
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS)17.3 score on a scaleStandard Deviation 30.06
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS)10.7 score on a scaleStandard Deviation 28.33
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS)11.3 score on a scaleStandard Deviation 26.09
p-value: 0.55895% CI: [-4.24, 7.86]Mixed Models Analysis
p-value: 0.23395% CI: [-2.34, 9.57]Mixed Models Analysis
p-value: 0.04395% CI: [0.2, 12.13]Mixed Models Analysis
p-value: 0.48895% CI: [-3.8, 7.95]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT)

Change from Baseline to Month 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT)-20.2 score on a scaleStandard Deviation 25.27
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT)-19.9 score on a scaleStandard Deviation 24.9
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT)-19.9 score on a scaleStandard Deviation 25.01
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT)-19.7 score on a scaleStandard Deviation 24.13
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT)-14.1 score on a scaleStandard Deviation 28.67
p-value: <0.00195% CI: [-13.76, -4.19]Mixed Models Analysis
p-value: <0.00195% CI: [-14.34, -4.85]Mixed Models Analysis
p-value: <0.00195% CI: [-14.03, -4.56]Mixed Models Analysis
p-value: 0.00295% CI: [-12.51, -2.93]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS)

Change from Baseline to Month 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS)-20.0 score on a scaleStandard Deviation 28.25
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS)-22.3 score on a scaleStandard Deviation 24.84
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS)-26.1 score on a scaleStandard Deviation 27.21
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS)-26.1 score on a scaleStandard Deviation 25.32
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS)-14.1 score on a scaleStandard Deviation 28.67
p-value: 0.0495% CI: [-12.8, -0.31]Mixed Models Analysis
p-value: 0.00195% CI: [-15.99, -4.04]Mixed Models Analysis
p-value: 0.00295% CI: [-16.11, -3.81]Mixed Models Analysis
p-value: 0.02995% CI: [-12.99, -0.7]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT)

Change from Baseline to Month 6 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT)-22.3 score on a scaleStandard Deviation 25.24
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT)-20.2 score on a scaleStandard Deviation 22.46
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT)-20.1 score on a scaleStandard Deviation 25.12
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT)-19.4 score on a scaleStandard Deviation 24.85
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT)-15.4 score on a scaleStandard Deviation 27.57
p-value: <0.00195% CI: [-12.72, -4.04]Mixed Models Analysis
p-value: <0.00195% CI: [-11.83, -3.2]Mixed Models Analysis
p-value: <0.00195% CI: [-11.63, -3.02]Mixed Models Analysis
p-value: 0.01195% CI: [-9.93, -1.27]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS)

Change from Baseline to Month 6 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS)-23.5 score on a scaleStandard Deviation 25.99
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS)-21.3 score on a scaleStandard Deviation 24.42
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS)-26.9 score on a scaleStandard Deviation 26.91
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS)-22.4 score on a scaleStandard Deviation 26.76
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS)-15.4 score on a scaleStandard Deviation 27.57
p-value: 0.00895% CI: [-13.14, -1.93]Mixed Models Analysis
p-value: 0.01695% CI: [-12.18, -1.26]Mixed Models Analysis
p-value: 0.00295% CI: [-14.28, -3.1]Mixed Models Analysis
p-value: 0.02895% CI: [-11.68, -0.68]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT)

Change from Baseline to Wk 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT)-21.0 score on a scaleStandard Deviation 23.74
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT)-18.1 score on a scaleStandard Deviation 24.62
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT)-18.7 score on a scaleStandard Deviation 23.11
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT)-17.3 score on a scaleStandard Deviation 24.88
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT)-14.9 score on a scaleStandard Deviation 26.57
p-value: <0.00195% CI: [-11.55, -3.13]Mixed Models Analysis
p-value: 0.00995% CI: [-9.8, -1.4]Mixed Models Analysis
p-value: 0.01695% CI: [-9.31, -0.95]Mixed Models Analysis
p-value: 0.15495% CI: [-7.22, 1.14]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS)

Change from Baseline to Wk 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS)-22.3 score on a scaleStandard Deviation 23.72
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS)-17.7 score on a scaleStandard Deviation 24.75
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS)-23.6 score on a scaleStandard Deviation 25.07
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS)-19.3 score on a scaleStandard Deviation 26.31
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS)-15.1 score on a scaleStandard Deviation 26.65
p-value: 0.0295% CI: [-11.92, -1.04]Mixed Models Analysis
p-value: 0.21695% CI: [-8.69, 1.97]Mixed Models Analysis
p-value: 0.03395% CI: [-11.22, -0.48]Mixed Models Analysis
p-value: 0.26595% CI: [-8.27, 2.28]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT)

Change from Baseline to Month 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT)-14.3 score on a scaleStandard Deviation 18.35
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT)-14.6 score on a scaleStandard Deviation 17.95
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT)-15.4 score on a scaleStandard Deviation 18.74
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT)-15.1 score on a scaleStandard Deviation 19.43
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT)-10.5 score on a scaleStandard Deviation 21.71
p-value: <0.00195% CI: [-9.91, -2.65]Mixed Models Analysis
p-value: <0.00195% CI: [-11.18, -3.98]Mixed Models Analysis
p-value: <0.00195% CI: [-11.02, -3.84]Mixed Models Analysis
p-value: <0.00195% CI: [-10.17, -2.91]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS)

Change from Baseline to Month 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS)-14.7 score on a scaleStandard Deviation 21.13
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS)-15.7 score on a scaleStandard Deviation 17.65
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS)-20.5 score on a scaleStandard Deviation 21.49
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS)-17.4 score on a scaleStandard Deviation 19.48
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS)-10.5 score on a scaleStandard Deviation 21.71
p-value: 0.08395% CI: [-8.96, 0.55]Mixed Models Analysis
p-value: 0.00295% CI: [-11.91, -2.81]Mixed Models Analysis
p-value: <0.00195% CI: [-12.6, -3.23]Mixed Models Analysis
p-value: 0.00595% CI: [-11.46, -2.1]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS)

Change from Baseline to Month 6 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS)-17.5 score on a scaleStandard Deviation 17.4
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS)-16.0 score on a scaleStandard Deviation 16.69
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS)-19.8 score on a scaleStandard Deviation 21.18
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS)-17.0 score on a scaleStandard Deviation 19.02
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS)-11.6 score on a scaleStandard Deviation 19.31
p-value: 0.01195% CI: [-9.57, -1.25]Mixed Models Analysis
p-value: 0.00895% CI: [-9.6, -1.48]Mixed Models Analysis
p-value: 0.00795% CI: [-9.9, -1.59]Mixed Models Analysis
p-value: 0.01195% CI: [-9.4, -1.24]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT)

Change from Baseline to Wk 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT)-15.1 score on a scaleStandard Deviation 17.64
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT)-13.0 score on a scaleStandard Deviation 17.38
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT)-13.9 score on a scaleStandard Deviation 17.4
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT)-13.4 score on a scaleStandard Deviation 18.47
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT)-11.8 score on a scaleStandard Deviation 19.48
p-value: 0.00495% CI: [-7.75, -1.44]Mixed Models Analysis
p-value: 0.0395% CI: [-6.64, -0.34]Mixed Models Analysis
p-value: 0.04995% CI: [-6.29, -0.02]Mixed Models Analysis
p-value: 0.12195% CI: [-5.61, 0.65]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS)

Change from Baseline to Wk 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS)-16.8 score on a scaleStandard Deviation 17.14
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS)-13.1 score on a scaleStandard Deviation 16.16
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS)-18.5 score on a scaleStandard Deviation 19.34
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS)-14.4 score on a scaleStandard Deviation 19.19
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS)-11.8 score on a scaleStandard Deviation 19.56
p-value: 0.03995% CI: [-8.21, -0.21]Mixed Models Analysis
p-value: 0.23295% CI: [-6.31, 1.53]Mixed Models Analysis
p-value: 0.0395% CI: [-8.32, -0.42]Mixed Models Analysis
p-value: 0.26295% CI: [-6.09, 1.66]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT)

Change from Baseline to Month 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT)-12.8 score on a scaleStandard Deviation 18.19
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT)-13.0 score on a scaleStandard Deviation 18.36
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT)-13.7 score on a scaleStandard Deviation 19.02
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT)-14.0 score on a scaleStandard Deviation 20.14
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT)-9.1 score on a scaleStandard Deviation 22.62
p-value: 0.00195% CI: [-9.71, -2.32]Mixed Models Analysis
p-value: <0.00195% CI: [-10.89, -3.55]Mixed Models Analysis
p-value: <0.00195% CI: [-10.58, -3.27]Mixed Models Analysis
p-value: <0.00195% CI: [-10.12, -2.72]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS)

Change from Baseline to Month 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS)-13.3 score on a scaleStandard Deviation 20.52
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS)-13.5 score on a scaleStandard Deviation 18.04
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS)-18.9 score on a scaleStandard Deviation 21.49
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS)-16.1 score on a scaleStandard Deviation 20.01
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS)-9.1 score on a scaleStandard Deviation 22.62
p-value: 0.17195% CI: [-8.24, 1.47]Mixed Models Analysis
p-value: 0.00695% CI: [-11.14, -1.85]Mixed Models Analysis
p-value: 0.00395% CI: [-12.17, -2.61]Mixed Models Analysis
p-value: 0.00695% CI: [-11.46, -1.92]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT)

Change from Baseline to Month 6 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT)-14.0 score on a scaleStandard Deviation 17.6
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT)-12.9 score on a scaleStandard Deviation 16.76
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT)-13.2 score on a scaleStandard Deviation 19.16
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT)-13.8 score on a scaleStandard Deviation 19.77
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT)-9.8 score on a scaleStandard Deviation 20.37
p-value: <0.00195% CI: [-9.05, -2.33]Mixed Models Analysis
p-value: 0.00195% CI: [-8.93, -2.24]Mixed Models Analysis
p-value: 0.00395% CI: [-8.45, -1.79]Mixed Models Analysis
p-value: 0.00395% CI: [-8.46, -1.76]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS)

Change from Baseline to Month 6 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS)-16.1 score on a scaleStandard Deviation 16.64
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS)-14.3 score on a scaleStandard Deviation 16.56
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS)-18.0 score on a scaleStandard Deviation 20.71
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS)-15.7 score on a scaleStandard Deviation 19.34
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS)-9.8 score on a scaleStandard Deviation 20.37
p-value: 0.01395% CI: [-9.52, -1.13]Mixed Models Analysis
p-value: 0.00695% CI: [-9.85, -1.68]Mixed Models Analysis
p-value: 0.00995% CI: [-9.77, -1.4]Mixed Models Analysis
p-value: 0.00795% CI: [-9.79, -1.57]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT)

Change from Baseline to Wk 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT)-13.5 score on a scaleStandard Deviation 17.9
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT)-11.4 score on a scaleStandard Deviation 18.02
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT)-12.2 score on a scaleStandard Deviation 18.29
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT)-12.8 score on a scaleStandard Deviation 19.33
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT)-9.8 score on a scaleStandard Deviation 20.47
p-value: 0.00395% CI: [-8.18, -1.65]Mixed Models Analysis
p-value: 0.02395% CI: [-7.05, -0.53]Mixed Models Analysis
p-value: 0.04795% CI: [-6.52, -0.04]Mixed Models Analysis
p-value: 0.03995% CI: [-6.65, -0.17]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS)

Change from Baseline to Wk 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS)-15.2 score on a scaleStandard Deviation 17.45
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS)-11.3 score on a scaleStandard Deviation 17.04
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS)-17.7 score on a scaleStandard Deviation 19.47
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS)-13.5 score on a scaleStandard Deviation 19.65
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS)-9.9 score on a scaleStandard Deviation 20.5
p-value: 0.05995% CI: [-8.13, 0.16]Mixed Models Analysis
p-value: 0.21595% CI: [-6.63, 1.49]Mixed Models Analysis
p-value: 0.01595% CI: [-9.19, -1]Mixed Models Analysis
p-value: 0.12295% CI: [-7.17, 0.85]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT)

Change from Baseline to Month 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT)-6.6 score on a scaleStandard Deviation 27.64
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT)-6.4 score on a scaleStandard Deviation 23.58
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT)-7.9 score on a scaleStandard Deviation 28.34
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT)-6.5 score on a scaleStandard Deviation 28.07
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT)-2.8 score on a scaleStandard Deviation 27.6
p-value: 0.38995% CI: [-6.42, 2.5]Mixed Models Analysis
p-value: 0.28195% CI: [-6.85, 1.99]Mixed Models Analysis
p-value: 0.50495% CI: [-5.92, 2.91]Mixed Models Analysis
p-value: 0.4695% CI: [-6.15, 2.78]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS)

Change from Baseline to Month 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS)-8.9 score on a scaleStandard Deviation 30.41
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS)-7.1 score on a scaleStandard Deviation 24.6
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS)-12.4 score on a scaleStandard Deviation 34.65
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS)-10.8 score on a scaleStandard Deviation 27.15
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS)-2.8 score on a scaleStandard Deviation 27.6
p-value: 0.37995% CI: [-8.44, 3.22]Mixed Models Analysis
p-value: 0.27995% CI: [-8.64, 2.49]Mixed Models Analysis
p-value: 0.89495% CI: [-6.19, 5.4]Mixed Models Analysis
p-value: 0.30895% CI: [-8.72, 2.76]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT)

Change from Baseline to Month 6 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT)-6.2 score on a scaleStandard Deviation 28.14
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT)-5.9 score on a scaleStandard Deviation 24.36
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT)-7.5 score on a scaleStandard Deviation 27.19
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT)-5.7 score on a scaleStandard Deviation 26.34
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT)-2.1 score on a scaleStandard Deviation 23.47
p-value: 0.25595% CI: [-6.71, 1.78]Mixed Models Analysis
p-value: 0.29395% CI: [-6.49, 1.96]Mixed Models Analysis
p-value: 0.50295% CI: [-5.66, 2.77]Mixed Models Analysis
p-value: 0.49595% CI: [-5.71, 2.76]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS)

Change from Baseline to Month 6 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS)-9.7 score on a scaleStandard Deviation 27.72
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS)-5.0 score on a scaleStandard Deviation 27.5
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS)-11.0 score on a scaleStandard Deviation 33.55
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS)-7.3 score on a scaleStandard Deviation 26.96
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS)-2.1 score on a scaleStandard Deviation 23.47
p-value: 0.07495% CI: [-10.48, 0.48]Mixed Models Analysis
p-value: 0.74895% CI: [-6.22, 4.47]Mixed Models Analysis
p-value: 0.98795% CI: [-5.46, 5.56]Mixed Models Analysis
p-value: 0.70995% CI: [-6.41, 4.36]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT)

Change from Baseline to Wk 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT)-6.0 score on a scaleStandard Deviation 24.56
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT)-6.0 score on a scaleStandard Deviation 23.67
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT)-7.1 score on a scaleStandard Deviation 27.97
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT)-6.3 score on a scaleStandard Deviation 27.03
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT)-3.4 score on a scaleStandard Deviation 25.5
p-value: 0.8395% CI: [-4.48, 3.59]Mixed Models Analysis
p-value: 0.75595% CI: [-4.66, 3.38]Mixed Models Analysis
p-value: 0.80295% CI: [-3.5, 4.53]Mixed Models Analysis
p-value: 0.82395% CI: [-4.46, 3.55]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS)

Change from Baseline to Wk 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS)-7.7 score on a scaleStandard Deviation 26.83
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS)-4.3 score on a scaleStandard Deviation 22.18
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS)-12.3 score on a scaleStandard Deviation 29.62
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS)-7.9 score on a scaleStandard Deviation 27.67
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS)-3.6 score on a scaleStandard Deviation 25.52
p-value: 0.63195% CI: [-6.34, 3.84]Mixed Models Analysis
p-value: 0.65195% CI: [-3.84, 6.14]Mixed Models Analysis
p-value: 0.81395% CI: [-5.67, 4.45]Mixed Models Analysis
p-value: 0.86995% CI: [-5.35, 4.52]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT)

Change from Baseline to Month 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT)-8.5 score on a scaleStandard Deviation 22.79
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT)-9.2 score on a scaleStandard Deviation 19.17
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT)-9.9 score on a scaleStandard Deviation 19.33
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT)-9.4 score on a scaleStandard Deviation 23.06
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT)-6.7 score on a scaleStandard Deviation 25.95
p-value: 0.09795% CI: [-7.34, 0.61]Mixed Models Analysis
p-value: 0.00895% CI: [-9.28, -1.4]Mixed Models Analysis
p-value: 0.01495% CI: [-8.87, -1.01]Mixed Models Analysis
p-value: 0.05695% CI: [-7.86, 0.1]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS)

Change from Baseline to Month 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS)-8.0 score on a scaleStandard Deviation 22.93
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS)-11.1 score on a scaleStandard Deviation 21.51
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS)-13.1 score on a scaleStandard Deviation 20.03
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS)-13.4 score on a scaleStandard Deviation 23.82
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS)-6.7 score on a scaleStandard Deviation 25.95
p-value: 0.41595% CI: [-7.46, 3.08]Mixed Models Analysis
p-value: 0.01995% CI: [-11.04, -0.97]Mixed Models Analysis
p-value: 0.07495% CI: [-9.9, 0.46]Mixed Models Analysis
p-value: 0.0395% CI: [-10.94, -0.57]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT)

Change from Baseline to Month 6 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT)-9.4 score on a scaleStandard Deviation 22.4
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT)-8.4 score on a scaleStandard Deviation 19.88
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT)-9.6 score on a scaleStandard Deviation 20.04
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT)-8.7 score on a scaleStandard Deviation 21.65
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT)-9.6 score on a scaleStandard Deviation 21.64
p-value: 0.57295% CI: [-4.86, 2.69]Mixed Models Analysis
p-value: 0.55395% CI: [-4.89, 2.62]Mixed Models Analysis
p-value: 0.45695% CI: [-5.16, 2.32]Mixed Models Analysis
p-value: 0.94995% CI: [-3.89, 3.64]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS)

Change from Baseline to Month 6 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS)-10.1 score on a scaleStandard Deviation 21.6
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS)-10.8 score on a scaleStandard Deviation 21.46
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS)-12.4 score on a scaleStandard Deviation 22.98
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS)-10.5 score on a scaleStandard Deviation 23.69
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS)-9.6 score on a scaleStandard Deviation 21.64
p-value: 0.68795% CI: [-5.86, 3.86]Mixed Models Analysis
p-value: 0.37395% CI: [-6.88, 2.58]Mixed Models Analysis
p-value: 0.71495% CI: [-5.75, 3.94]Mixed Models Analysis
p-value: 0.71195% CI: [-5.67, 3.87]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT)

Change from Baseline to Wk 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT)-9.2 score on a scaleStandard Deviation 20.49
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT)-8.1 score on a scaleStandard Deviation 18.67
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT)-7.6 score on a scaleStandard Deviation 19.57
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT)-8.9 score on a scaleStandard Deviation 21.09
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT)-8.7 score on a scaleStandard Deviation 20.54
p-value: 0.34995% CI: [-5.07, 1.79]Mixed Models Analysis
p-value: 0.49995% CI: [-4.6, 2.24]Mixed Models Analysis
p-value: 0.93695% CI: [-3.27, 3.55]Mixed Models Analysis
p-value: 0.69695% CI: [-4.08, 2.72]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS)

Change from Baseline to Wk 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS)-11.3 score on a scaleStandard Deviation 20.7
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS)-9.2 score on a scaleStandard Deviation 17.82
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS)-10.4 score on a scaleStandard Deviation 22.61
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS)-10.8 score on a scaleStandard Deviation 21.78
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS)-8.7 score on a scaleStandard Deviation 20.62
p-value: 0.22195% CI: [-7, 1.62]Mixed Models Analysis
p-value: 0.51195% CI: [-5.65, 2.81]Mixed Models Analysis
p-value: 0.76195% CI: [-3.6, 4.92]Mixed Models Analysis
p-value: 0.33295% CI: [-6.25, 2.11]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT)

Change from Baseline to Month 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT)-3.4 score on a scaleStandard Deviation 29.62
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT)-7.5 score on a scaleStandard Deviation 27.71
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT)-5.0 score on a scaleStandard Deviation 28.57
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT)-4.5 score on a scaleStandard Deviation 24.79
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT)-4.5 score on a scaleStandard Deviation 26.23
p-value: 0.66295% CI: [-4.36, 6.87]Mixed Models Analysis
p-value: 0.63595% CI: [-6.91, 4.21]Mixed Models Analysis
p-value: 0.87795% CI: [-5.98, 5.11]Mixed Models Analysis
p-value: 0.89395% CI: [-6.01, 5.24]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS)

Change from Baseline to Month 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS)-1.1 score on a scaleStandard Deviation 28.04
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS)-10.5 score on a scaleStandard Deviation 29.43
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS)-6.2 score on a scaleStandard Deviation 27.03
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS)-8.0 score on a scaleStandard Deviation 26.77
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS)-4.5 score on a scaleStandard Deviation 26.23
p-value: 0.57995% CI: [-4.85, 8.67]Mixed Models Analysis
p-value: 0.22395% CI: [-10.43, 2.44]Mixed Models Analysis
p-value: 0.54295% CI: [-8.67, 4.56]Mixed Models Analysis
p-value: 0.47695% CI: [-9.04, 4.23]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT)

Change from Baseline to Month 6 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT)-2.4 score on a scaleStandard Deviation 28
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT)-6.0 score on a scaleStandard Deviation 25.73
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT)-6.8 score on a scaleStandard Deviation 27.32
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT)-3.7 score on a scaleStandard Deviation 28.98
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT)-3.5 score on a scaleStandard Deviation 27.08
p-value: 0.92795% CI: [-5.08, 5.58]Mixed Models Analysis
p-value: 0.54195% CI: [-6.95, 3.64]Mixed Models Analysis
p-value: 0.17195% CI: [-8.96, 1.6]Mixed Models Analysis
p-value: 0.66795% CI: [-6.48, 4.15]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS)

Change from Baseline to Month 6 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS)0.7 score on a scaleStandard Deviation 26.29
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS)-5.5 score on a scaleStandard Deviation 26.24
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS)-8.8 score on a scaleStandard Deviation 24.47
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS)-6.1 score on a scaleStandard Deviation 30.29
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS)-3.5 score on a scaleStandard Deviation 27.08
p-value: 0.57395% CI: [-4.51, 8.14]Mixed Models Analysis
p-value: 0.76995% CI: [-7.01, 5.19]Mixed Models Analysis
p-value: 0.04795% CI: [-12.56, -0.09]Mixed Models Analysis
p-value: 0.40995% CI: [-8.74, 3.56]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT)

Change from Baseline to Wk 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT)-2.6 score on a scaleStandard Deviation 25.3
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT)-4.7 score on a scaleStandard Deviation 26.08
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT)-4.5 score on a scaleStandard Deviation 28.93
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT)-3.4 score on a scaleStandard Deviation 26.94
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT)-5.6 score on a scaleStandard Deviation 25.03
p-value: 0.43495% CI: [-3.03, 7.07]Mixed Models Analysis
p-value: 0.44295% CI: [-3.06, 7]Mixed Models Analysis
p-value: 0.55895% CI: [-3.52, 6.51]Mixed Models Analysis
p-value: 0.53495% CI: [-3.42, 6.6]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS)

Change from Baseline to Wk 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0=best possible & 100=worst possible. MOS\_n\_new \<- (6-MOS\_n\_old) x 20. Score range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS)-0.5 score on a scaleStandard Deviation 23.73
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS)-3.6 score on a scaleStandard Deviation 25.84
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS)-7.1 score on a scaleStandard Deviation 28.49
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS)-5.7 score on a scaleStandard Deviation 24.65
PlaceboMedical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS)-5.7 score on a scaleStandard Deviation 25.13
p-value: 0.29495% CI: [-2.75, 9.05]Mixed Models Analysis
p-value: 0.32795% CI: [-2.87, 8.6]Mixed Models Analysis
p-value: 0.63795% CI: [-7.18, 4.39]Mixed Models Analysis
p-value: 0.95295% CI: [-5.51, 5.86]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT)

Change from Baseline (BL) to Month 12 in MOS Optimal Sleep Score as compared with Placebo.The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT)0.1 Proportion of Net ChangeStandard Deviation 0.51
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT)0.2 Proportion of Net ChangeStandard Deviation 0.56
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT)0.1 Proportion of Net ChangeStandard Deviation 0.55
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT)0.1 Proportion of Net ChangeStandard Deviation 0.52
PlaceboMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT)0.2 Proportion of Net ChangeStandard Deviation 0.47
p-value: 0.99295% CI: [-0.11, 0.11]Mixed Models Analysis
p-value: 0.4595% CI: [-0.07, 0.15]Mixed Models Analysis
p-value: 0.66395% CI: [-0.13, 0.08]Mixed Models Analysis
p-value: 0.30995% CI: [-0.16, 0.05]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS)

Change from Baseline (BL) to Month 12 in MOS Optimal Sleep Score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.47
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS)0.3 Proportion of Net ChangeStandard Deviation 0.58
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS)0.1 Proportion of Net ChangeStandard Deviation 0.57
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS)0.1 Proportion of Net ChangeStandard Deviation 0.51
PlaceboMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.47
p-value: 0.45295% CI: [-0.18, 0.08]Mixed Models Analysis
p-value: 0.24495% CI: [-0.05, 0.2]Mixed Models Analysis
p-value: 0.35495% CI: [-0.19, 0.07]Mixed Models Analysis
p-value: 0.52795% CI: [-0.17, 0.09]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT)

Change from Baseline (BL) to Month 6 in MOS Optimal Sleep Score as compared with Placebo.The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT)0.2 Proportion of Net ChangeStandard Deviation 0.56
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT)0.2 Proportion of Net ChangeStandard Deviation 0.55
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT)0.2 Proportion of Net ChangeStandard Deviation 0.53
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT)0.1 Proportion of Net ChangeStandard Deviation 0.56
PlaceboMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT)0.2 Proportion of Net ChangeStandard Deviation 0.52
p-value: 0.04595% CI: [0, 0.21]Mixed Models Analysis
p-value: 0.06995% CI: [-0.01, 0.2]Mixed Models Analysis
p-value: 0.12695% CI: [-0.02, 0.18]Mixed Models Analysis
p-value: 0.90795% CI: [-0.1, 0.11]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS)

Change from Baseline (BL) to Month 6 in MOS Optimal Sleep Score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS)0.3 Proportion of Net ChangeStandard Deviation 0.52
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.52
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.57
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS)0.1 Proportion of Net ChangeStandard Deviation 0.57
PlaceboMedical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.52
p-value: 0.07595% CI: [-0.01, 0.24]Mixed Models Analysis
p-value: 0.07495% CI: [-0.01, 0.23]Mixed Models Analysis
p-value: 0.3795% CI: [-0.07, 0.18]Mixed Models Analysis
p-value: 0.85195% CI: [-0.11, 0.13]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT)

Change from Baseline (BL) to Wk 12 in MOS Optimal Sleep Score as compared with Placebo.The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT)0.2 Proportion of Net ChangeStandard Deviation 0.53
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT)0.1 Proportion of Net ChangeStandard Deviation 0.56
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT)0.2 Proportion of Net ChangeStandard Deviation 0.49
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT)0.1 Proportion of Net ChangeStandard Deviation 0.52
PlaceboMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT)0.2 Proportion of Net ChangeStandard Deviation 0.59
p-value: 0.22595% CI: [-0.04, 0.16]Mixed Models Analysis
p-value: 0.74195% CI: [-0.08, 0.11]Mixed Models Analysis
p-value: 0.41495% CI: [-0.06, 0.14]Mixed Models Analysis
p-value: 0.6995% CI: [-0.11, 0.08]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS)

Change from Baseline (BL) to Week 12 in MOS Optimal Sleep Score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where \>0 = overall improvement and \<0 = overall worsening in the study arm.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.55
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.54
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.45
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.53
PlaceboMedical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS)0.2 Proportion of Net ChangeStandard Deviation 0.58
p-value: 0.93895% CI: [-0.12, 0.11]Mixed Models Analysis
p-value: 0.77995% CI: [-0.1, 0.13]Mixed Models Analysis
p-value: 0.64695% CI: [-0.14, 0.09]Mixed Models Analysis
p-value: 0.42195% CI: [-0.07, 0.16]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT)

Change from Baseline to Month 6 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT)-15.5 score on a scaleStandard Deviation 18.15
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT)-14.6 score on a scaleStandard Deviation 16.41
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT)-14.9 score on a scaleStandard Deviation 18.95
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT)-14.8 score on a scaleStandard Deviation 18.87
PlaceboMedical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT)-11.6 score on a scaleStandard Deviation 19.31
p-value: 0.00195% CI: [-8.74, -2.14]Mixed Models Analysis
p-value: <0.00195% CI: [-8.81, -2.25]Mixed Models Analysis
p-value: 0.00295% CI: [-8.39, -1.85]Mixed Models Analysis
p-value: 0.00695% CI: [-7.93, -1.35]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT)

Change from Baseline to Month 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT)-14.4 score on a scaleStandard Deviation 18.36
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT)-14.5 score on a scaleStandard Deviation 17.85
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT)-15.3 score on a scaleStandard Deviation 18.78
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT)-15.3 score on a scaleStandard Deviation 19.28
PlaceboMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT)-10.3 score on a scaleStandard Deviation 21.78
p-value: <0.00195% CI: [-10.18, -2.9]Mixed Models Analysis
p-value: <0.00195% CI: [-11.23, -4]Mixed Models Analysis
p-value: <0.00195% CI: [-11.04, -3.84]Mixed Models Analysis
p-value: <0.00195% CI: [-10.41, -3.1]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS)

Change from Baseline to Month 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS)-14.9 score on a scaleStandard Deviation 21.09
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS)-15.8 score on a scaleStandard Deviation 17.72
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS)-20.6 score on a scaleStandard Deviation 21.58
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS)-17.6 score on a scaleStandard Deviation 18.81
PlaceboMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS)-10.3 score on a scaleStandard Deviation 21.78
p-value: 0.05895% CI: [-9.38, 0.16]Mixed Models Analysis
p-value: 0.00195% CI: [-12.04, -2.92]Mixed Models Analysis
p-value: <0.00195% CI: [-12.67, -3.25]Mixed Models Analysis
p-value: 0.00595% CI: [-11.5, -2.06]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT)

Change from Baseline to Month 6 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT)-15.6 score on a scaleStandard Deviation 18.13
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT)-14.8 score on a scaleStandard Deviation 16.1
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT)-14.7 score on a scaleStandard Deviation 18.95
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT)-14.6 score on a scaleStandard Deviation 18.93
PlaceboMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT)-11.7 score on a scaleStandard Deviation 19.4
p-value: 0.00295% CI: [-8.73, -2.05]Mixed Models Analysis
p-value: 0.00295% CI: [-8.72, -2.06]Mixed Models Analysis
p-value: 0.00495% CI: [-8.19, -1.58]Mixed Models Analysis
p-value: 0.00995% CI: [-7.75, -1.09]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS)

Change from Baseline to Month 6 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS)-17.8 score on a scaleStandard Deviation 17.28
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS)-16.0 score on a scaleStandard Deviation 16.6
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS)-19.8 score on a scaleStandard Deviation 21.18
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS)-16.6 score on a scaleStandard Deviation 19.01
PlaceboMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS)-11.7 score on a scaleStandard Deviation 19.4
p-value: 0.01195% CI: [-9.68, -1.28]Mixed Models Analysis
p-value: 0.01295% CI: [-9.36, -1.14]Mixed Models Analysis
p-value: 0.00995% CI: [-9.75, -1.41]Mixed Models Analysis
p-value: 0.01895% CI: [-9.11, -0.87]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT)

Change from Baseline to Wk 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT)-15.1 score on a scaleStandard Deviation 17.64
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT)-13.0 score on a scaleStandard Deviation 17.42
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT)-13.9 score on a scaleStandard Deviation 17.4
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT)-13.3 score on a scaleStandard Deviation 18.22
PlaceboMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT)-11.5 score on a scaleStandard Deviation 19.6
p-value: 0.00395% CI: [-8.08, -1.69]Mixed Models Analysis
p-value: 0.02795% CI: [-6.8, -0.42]Mixed Models Analysis
p-value: 0.03495% CI: [-6.61, -0.26]Mixed Models Analysis
p-value: 0.11995% CI: [-5.71, 0.65]Mixed Models Analysis
Secondary

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS)

Change from Baseline to Wk 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=\>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0=best possible & 100=worst possible as follows: MOS\_n\_new = (6-MOS\_n\_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS\_1\_new =(MOS\_1\_old - 1) x 25; MOS\_4\_new =(MOS\_4\_old - 1) x 20; MOS\_12\_new=(MOS\_12\_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS)-16.7 score on a scaleStandard Deviation 16.99
Combined Estradiol 0.5 mg / Progesterone 100 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS)-13.1 score on a scaleStandard Deviation 16.22
Combined Estradiol 0.5 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS)-18.5 score on a scaleStandard Deviation 19.41
Combined Estradiol 0.25 mg / Progesterone 50 mgMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS)-14.6 score on a scaleStandard Deviation 18.8
PlaceboMedical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS)-11.5 score on a scaleStandard Deviation 19.67
p-value: 0.03395% CI: [-8.44, -0.35]Mixed Models Analysis
p-value: 0.20795% CI: [-6.5, 1.41]Mixed Models Analysis
p-value: 0.02495% CI: [-8.58, -0.61]Mixed Models Analysis
p-value: 0.20795% CI: [-6.47, 1.41]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT)

Change in Overall Scores from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT)-1.8 score on a scaleStandard Deviation 1.43
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT)-1.8 score on a scaleStandard Deviation 1.45
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT)-1.7 score on a scaleStandard Deviation 1.38
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT)-1.6 score on a scaleStandard Deviation 1.38
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT)-1.5 score on a scaleStandard Deviation 1.5
p-value: <0.00195% CI: [-0.89, -0.36]Mixed Models Analysis
p-value: <0.00195% CI: [-0.88, -0.36]Mixed Models Analysis
p-value: <0.00195% CI: [-0.73, -0.21]Mixed Models Analysis
p-value: 0.00695% CI: [-0.63, -0.1]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS)

Changes in Overall Scores from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS)-1.8 score on a scaleStandard Deviation 1.45
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS)-2.0 score on a scaleStandard Deviation 1.27
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS)-2.0 score on a scaleStandard Deviation 1.5
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS)-1.7 score on a scaleStandard Deviation 1.29
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS)-1.5 score on a scaleStandard Deviation 1.5
p-value: 0.01295% CI: [-0.76, -0.1]Mixed Models Analysis
p-value: <0.00195% CI: [-1.05, -0.41]Mixed Models Analysis
p-value: 0.00495% CI: [-0.81, -0.16]Mixed Models Analysis
p-value: 0.0795% CI: [-0.63, 0.03]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT)

Change in Overall Scores from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT)-2.0 score on a scaleStandard Deviation 1.32
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT)-1.8 score on a scaleStandard Deviation 1.38
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT)-1.8 score on a scaleStandard Deviation 1.39
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT)-1.7 score on a scaleStandard Deviation 1.29
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT)-1.6 score on a scaleStandard Deviation 1.31
p-value: <0.00195% CI: [-0.85, -0.38]Mixed Models Analysis
p-value: <0.00195% CI: [-0.69, -0.22]Mixed Models Analysis
p-value: 0.00395% CI: [-0.59, -0.12]Mixed Models Analysis
p-value: 0.0395% CI: [-0.5, -0.03]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS)

Changes in Overall Scores from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS)-2.0 score on a scaleStandard Deviation 1.22
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS)-1.8 score on a scaleStandard Deviation 1.22
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS)-2.1 score on a scaleStandard Deviation 1.5
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS)-1.7 score on a scaleStandard Deviation 1.24
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS)-1.6 score on a scaleStandard Deviation 1.31
p-value: <0.00195% CI: [-0.84, -0.25]Mixed Models Analysis
p-value: 0.00495% CI: [-0.71, -0.13]Mixed Models Analysis
p-value: 0.00395% CI: [-0.73, -0.14]Mixed Models Analysis
p-value: 0.17995% CI: [-0.49, 0.09]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT)

Change in Overall Scores from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT)-1.8 score on a scaleStandard Deviation 1.31
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT)-1.6 score on a scaleStandard Deviation 1.38
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT)-1.7 score on a scaleStandard Deviation 1.35
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT)-1.6 score on a scaleStandard Deviation 1.35
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT)-1.4 score on a scaleStandard Deviation 1.36
p-value: <0.00195% CI: [-0.85, -0.4]Mixed Models Analysis
p-value: <0.00195% CI: [-0.71, -0.26]Mixed Models Analysis
p-value: <0.00195% CI: [-0.75, -0.3]Mixed Models Analysis
p-value: <0.00195% CI: [-0.64, -0.2]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS)

Changes in Overall Scores from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS)-1.9 score on a scaleStandard Deviation 1.2
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS)-1.6 score on a scaleStandard Deviation 1.23
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS)-1.9 score on a scaleStandard Deviation 1.41
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS)-1.7 score on a scaleStandard Deviation 1.31
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS)-1.4 score on a scaleStandard Deviation 1.36
p-value: <0.00195% CI: [-0.87, -0.29]Mixed Models Analysis
p-value: 0.01695% CI: [-0.62, -0.06]Mixed Models Analysis
p-value: <0.00195% CI: [-0.76, -0.2]Mixed Models Analysis
p-value: 0.02395% CI: [-0.6, -0.05]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT)

Changes in Physical Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT)-1.1 score on a scaleStandard Deviation 1.52
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT)-1.1 score on a scaleStandard Deviation 1.48
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT)-1.2 score on a scaleStandard Deviation 1.43
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT)-1.1 score on a scaleStandard Deviation 1.5
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT)-0.9 score on a scaleStandard Deviation 1.39
p-value: 0.0695% CI: [-0.53, 0.01]Mixed Models Analysis
p-value: 0.02695% CI: [-0.57, -0.04]Mixed Models Analysis
p-value: 0.09795% CI: [-0.49, 0.04]Mixed Models Analysis
p-value: 0.2395% CI: [-0.44, 0.1]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS)

Changes in Physical Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.57
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS)-1.2 score on a scaleStandard Deviation 1.29
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS)-1.4 score on a scaleStandard Deviation 1.6
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.44
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS)-0.9 score on a scaleStandard Deviation 1.39
p-value: 0.63595% CI: [-0.42, 0.26]Mixed Models Analysis
p-value: 0.0195% CI: [-0.75, -0.1]Mixed Models Analysis
p-value: 0.09295% CI: [-0.62, 0.05]Mixed Models Analysis
p-value: 0.24395% CI: [-0.53, 0.13]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT)

Changes in Physical Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT)-1.2 score on a scaleStandard Deviation 1.42
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT)-1.1 score on a scaleStandard Deviation 1.46
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT)-1.2 score on a scaleStandard Deviation 1.46
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT)-1.0 score on a scaleStandard Deviation 1.39
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT)-1.1 score on a scaleStandard Deviation 1.4
p-value: 0.05695% CI: [-0.48, 0.01]Mixed Models Analysis
p-value: 0.27995% CI: [-0.38, 0.11]Mixed Models Analysis
p-value: 0.43595% CI: [-0.34, 0.15]Mixed Models Analysis
p-value: 0.60795% CI: [-0.31, 0.18]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS)

Changes in Physical Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS)-1.2 score on a scaleStandard Deviation 1.32
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.37
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS)-1.5 score on a scaleStandard Deviation 1.61
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.28
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.4
p-value: 0.19795% CI: [-0.49, 0.1]Mixed Models Analysis
p-value: 0.30895% CI: [-0.44, 0.14]Mixed Models Analysis
p-value: 0.11795% CI: [-0.54, 0.06]Mixed Models Analysis
p-value: 0.73995% CI: [-0.34, 0.24]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT)

Changes in Physical Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT)-1.1 score on a scaleStandard Deviation 1.41
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT)-1.1 score on a scaleStandard Deviation 1.44
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT)-1.3 score on a scaleStandard Deviation 1.4
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT)-1.1 score on a scaleStandard Deviation 1.39
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT)-1.0 score on a scaleStandard Deviation 1.38
p-value: 0.18195% CI: [-0.38, 0.07]Mixed Models Analysis
p-value: 0.10895% CI: [-0.41, 0.04]Mixed Models Analysis
p-value: 0.01495% CI: [-0.51, -0.06]Mixed Models Analysis
p-value: 0.32395% CI: [-0.34, 0.11]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS)

Changes in Physical Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.3
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.32
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS)-1.5 score on a scaleStandard Deviation 1.5
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.3
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.38
p-value: 0.47495% CI: [-0.38, 0.18]Mixed Models Analysis
p-value: 0.37895% CI: [-0.4, 0.15]Mixed Models Analysis
p-value: 0.01895% CI: [-0.61, -0.06]Mixed Models Analysis
p-value: 0.7395% CI: [-0.32, 0.22]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT)

Changes in Psychosocial Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT)-1.1 score on a scaleStandard Deviation 1.65
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT)-1.1 score on a scaleStandard Deviation 1.74
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT)-1.1 score on a scaleStandard Deviation 1.66
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT)-1.0 score on a scaleStandard Deviation 1.64
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT)-1.0 score on a scaleStandard Deviation 1.61
p-value: 0.15395% CI: [-0.52, 0.08]Mixed Models Analysis
p-value: 0.05895% CI: [-0.58, 0.01]Mixed Models Analysis
p-value: 0.5595% CI: [-0.39, 0.21]Mixed Models Analysis
p-value: 0.85495% CI: [-0.33, 0.27]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS)

Changes in Psychosocial Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.51
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS)-1.3 score on a scaleStandard Deviation 1.61
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.84
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.67
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.61
p-value: 0.2595% CI: [-0.57, 0.15]Mixed Models Analysis
p-value: 0.00295% CI: [-0.88, -0.2]Mixed Models Analysis
p-value: 0.79695% CI: [-0.4, 0.31]Mixed Models Analysis
p-value: 0.95595% CI: [-0.36, 0.34]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT)

Changes in Psychosocial Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT)-1.3 score on a scaleStandard Deviation 1.68
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT)-1.1 score on a scaleStandard Deviation 1.65
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT)-1.1 score on a scaleStandard Deviation 1.65
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT)-1.0 score on a scaleStandard Deviation 1.55
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT)-1.0 score on a scaleStandard Deviation 1.61
p-value: 0.02395% CI: [-0.59, -0.04]Mixed Models Analysis
p-value: 0.04595% CI: [-0.55, -0.01]Mixed Models Analysis
p-value: 0.38495% CI: [-0.39, 0.15]Mixed Models Analysis
p-value: 0.42495% CI: [-0.38, 0.16]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS)

Changes in Psychosocial Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS)-1.3 score on a scaleStandard Deviation 1.64
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.44
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.76
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.57
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.61
p-value: 0.0495% CI: [-0.68, -0.02]Mixed Models Analysis
p-value: 0.06695% CI: [-0.63, 0.02]Mixed Models Analysis
p-value: 0.46995% CI: [-0.45, 0.21]Mixed Models Analysis
p-value: 0.61695% CI: [-0.41, 0.24]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT)

Changes in Psychosocial Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT)-1.1 score on a scaleStandard Deviation 1.52
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT)-1.0 score on a scaleStandard Deviation 1.66
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT)-1.1 score on a scaleStandard Deviation 1.58
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT)-1.0 score on a scaleStandard Deviation 1.49
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT)-1.0 score on a scaleStandard Deviation 1.68
p-value: 0.12695% CI: [-0.46, 0.06]Mixed Models Analysis
p-value: 0.295% CI: [-0.42, 0.09]Mixed Models Analysis
p-value: 0.22295% CI: [-0.41, 0.1]Mixed Models Analysis
p-value: 0.35895% CI: [-0.37, 0.14]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS)

Changes in Psychosocial Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.42
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS)-0.9 score on a scaleStandard Deviation 1.56
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS)-1.2 score on a scaleStandard Deviation 1.69
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.36
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS)-1.0 score on a scaleStandard Deviation 1.66
p-value: 0.28495% CI: [-0.49, 0.14]Mixed Models Analysis
p-value: 0.73295% CI: [-0.36, 0.26]Mixed Models Analysis
p-value: 0.43795% CI: [-0.44, 0.19]Mixed Models Analysis
p-value: 0.43995% CI: [-0.43, 0.19]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT)

Changes in Sexual Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT)-1.3 score on a scaleStandard Deviation 2.26
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT)-1.4 score on a scaleStandard Deviation 2.32
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT)-1.3 score on a scaleStandard Deviation 2.1
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT)-1.2 score on a scaleStandard Deviation 2.25
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT)-1.1 score on a scaleStandard Deviation 2.29
p-value: 0.02995% CI: [-0.84, -0.05]Mixed Models Analysis
p-value: 0.02695% CI: [-0.84, -0.05]Mixed Models Analysis
p-value: 0.09395% CI: [-0.72, 0.06]Mixed Models Analysis
p-value: 0.22395% CI: [-0.64, 0.15]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS)

Changes in Sexual Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS)-1.0 score on a scaleStandard Deviation 2.44
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS)-1.5 score on a scaleStandard Deviation 2.2
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS)-1.5 score on a scaleStandard Deviation 2.26
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS)-1.4 score on a scaleStandard Deviation 2.19
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS)-1.1 score on a scaleStandard Deviation 2.29
p-value: 0.42195% CI: [-0.71, 0.3]Mixed Models Analysis
p-value: 0.04495% CI: [-0.97, -0.01]Mixed Models Analysis
p-value: 0.09395% CI: [-0.92, 0.07]Mixed Models Analysis
p-value: 0.24795% CI: [-0.79, 0.2]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT)

Changes in Sexual Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT)-1.4 score on a scaleStandard Deviation 2.11
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT)-1.4 score on a scaleStandard Deviation 2.12
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT)-1.4 score on a scaleStandard Deviation 2.05
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT)-1.3 score on a scaleStandard Deviation 2.1
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT)-1.3 score on a scaleStandard Deviation 1.93
p-value: 0.08195% CI: [-0.65, 0.04]Mixed Models Analysis
p-value: 0.21295% CI: [-0.56, 0.12]Mixed Models Analysis
p-value: 0.34595% CI: [-0.51, 0.18]Mixed Models Analysis
p-value: 0.82995% CI: [-0.38, 0.31]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS)

Changes in Sexual Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS)-1.3 score on a scaleStandard Deviation 2.18
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS)-1.2 score on a scaleStandard Deviation 2.03
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS)-1.6 score on a scaleStandard Deviation 2.12
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS)-1.4 score on a scaleStandard Deviation 2.13
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS)-1.3 score on a scaleStandard Deviation 1.93
p-value: 0.22195% CI: [-0.7, 0.16]Mixed Models Analysis
p-value: 0.99295% CI: [-0.42, 0.42]Mixed Models Analysis
p-value: 0.18195% CI: [-0.72, 0.14]Mixed Models Analysis
p-value: 0.84695% CI: [-0.47, 0.38]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT)

Changes in Sexual Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT)-1.4 score on a scaleStandard Deviation 2.06
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT)-1.3 score on a scaleStandard Deviation 2.21
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT)-1.5 score on a scaleStandard Deviation 2.02
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT)-1.5 score on a scaleStandard Deviation 2.15
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT)-1.3 score on a scaleStandard Deviation 2.21
p-value: 0.10795% CI: [-0.61, 0.06]Mixed Models Analysis
p-value: 0.30295% CI: [-0.51, 0.16]Mixed Models Analysis
p-value: 0.10695% CI: [-0.6, 0.06]Mixed Models Analysis
p-value: 0.15695% CI: [-0.57, 0.09]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS)

Changes in Sexual Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS)-1.5 score on a scaleStandard Deviation 2.03
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS)-1.1 score on a scaleStandard Deviation 1.98
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS)-1.7 score on a scaleStandard Deviation 2.04
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS)-1.4 score on a scaleStandard Deviation 2.16
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS)-1.3 score on a scaleStandard Deviation 2.22
p-value: 0.04995% CI: [-0.83, 0]Mixed Models Analysis
p-value: 0.77395% CI: [-0.34, 0.46]Mixed Models Analysis
p-value: 0.08195% CI: [-0.77, 0.05]Mixed Models Analysis
p-value: 0.62595% CI: [-0.5, 0.3]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT)

Changes in Vasomotor Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT)-3.8 score on a scaleStandard Deviation 2.05
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT)-3.7 score on a scaleStandard Deviation 1.89
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT)-3.4 score on a scaleStandard Deviation 2.06
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT)-3.3 score on a scaleStandard Deviation 1.8
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT)-2.8 score on a scaleStandard Deviation 2.26
p-value: <0.00195% CI: [-2.06, -1.25]Mixed Models Analysis
p-value: <0.00195% CI: [-1.87, -1.07]Mixed Models Analysis
p-value: <0.00195% CI: [-1.7, -0.9]Mixed Models Analysis
p-value: <0.00195% CI: [-1.48, -0.67]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS)

Changes in Vasomotor Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS)-4.0 score on a scaleStandard Deviation 2.15
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS)-4.1 score on a scaleStandard Deviation 1.77
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS)-4.0 score on a scaleStandard Deviation 2.11
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS)-3.4 score on a scaleStandard Deviation 1.75
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS)-2.8 score on a scaleStandard Deviation 2.26
p-value: <0.00195% CI: [-1.75, -0.66]Mixed Models Analysis
p-value: <0.00195% CI: [-1.98, -0.94]Mixed Models Analysis
p-value: <0.00195% CI: [-1.76, -0.69]Mixed Models Analysis
p-value: 0.00895% CI: [-1.26, -0.19]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT)

Changes in Vasomotor Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT)-4.0 score on a scaleStandard Deviation 1.95
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT)-3.7 score on a scaleStandard Deviation 2.02
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT)-3.5 score on a scaleStandard Deviation 2.15
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT)-3.3 score on a scaleStandard Deviation 1.94
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT)-3.0 score on a scaleStandard Deviation 2.26
p-value: <0.00195% CI: [-2.12, -1.34]Mixed Models Analysis
p-value: <0.00195% CI: [-1.68, -0.91]Mixed Models Analysis
p-value: <0.00195% CI: [-1.58, -0.81]Mixed Models Analysis
p-value: <0.00195% CI: [-1.34, -0.57]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS)

Changes in Vasomotor Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Month 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS)-4.3 score on a scaleStandard Deviation 1.94
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS)-4.1 score on a scaleStandard Deviation 1.99
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS)-4.0 score on a scaleStandard Deviation 2.12
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS)-3.5 score on a scaleStandard Deviation 1.95
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS)-3.0 score on a scaleStandard Deviation 2.26
p-value: <0.00195% CI: [-1.91, -0.89]Mixed Models Analysis
p-value: <0.00195% CI: [-1.81, -0.82]Mixed Models Analysis
p-value: <0.00195% CI: [-1.63, -0.62]Mixed Models Analysis
p-value: 0.00795% CI: [-1.19, -0.19]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT)

Changes in Vasomotor Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: All randomized subjects who took at least one dose (2 capsules) of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT)-3.5 score on a scaleStandard Deviation 2.02
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT)-3.1 score on a scaleStandard Deviation 2
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT)-3.1 score on a scaleStandard Deviation 2.01
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT)-2.9 score on a scaleStandard Deviation 1.94
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT)-2.2 score on a scaleStandard Deviation 1.84
p-value: <0.00195% CI: [-2.29, -1.55]Mixed Models Analysis
p-value: <0.00195% CI: [-1.81, -1.07]Mixed Models Analysis
p-value: <0.00195% CI: [-1.81, -1.07]Mixed Models Analysis
p-value: <0.00195% CI: [-1.62, -0.88]Mixed Models Analysis
Secondary

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS)

Changes in Vasomotor Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being not at all bothered and 8 being extremely bothered.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS)-3.8 Score on a ScaleStandard Deviation 1.98
Combined Estradiol 0.5 mg / Progesterone 100 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS)-3.3 Score on a ScaleStandard Deviation 2.04
Combined Estradiol 0.5 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS)-3.3 Score on a ScaleStandard Deviation 1.97
Combined Estradiol 0.25 mg / Progesterone 50 mgMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS)-3.2 Score on a ScaleStandard Deviation 2.13
PlaceboMenopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS)-2.2 Score on a ScaleStandard Deviation 1.83
p-value: <0.00195% CI: [-2.13, -1.17]Mixed Models Analysis
p-value: <0.00195% CI: [-1.79, -0.84]Mixed Models Analysis
p-value: <0.00195% CI: [-1.64, -0.69]Mixed Models Analysis
p-value: <0.00195% CI: [-1.51, -0.58]Mixed Models Analysis
Secondary

Number of Days With Bleeding - Trimester 1 (Safety Pop.)

Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 1

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 1. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Days With Bleeding - Trimester 1 (Safety Pop.)1.2 DaysStandard Deviation 5.22
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Days With Bleeding - Trimester 1 (Safety Pop.)0.5 DaysStandard Deviation 2.21
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Days With Bleeding - Trimester 1 (Safety Pop.)0.5 DaysStandard Deviation 2.24
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Days With Bleeding - Trimester 1 (Safety Pop.)0.4 DaysStandard Deviation 1.79
PlaceboNumber of Days With Bleeding - Trimester 1 (Safety Pop.)0.2 DaysStandard Deviation 1.01
Secondary

Number of Days With Bleeding - Trimester 2 (Safety Pop.)

Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 2

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 2. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Days With Bleeding - Trimester 2 (Safety Pop.)0.9 DaysStandard Deviation 3.22
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Days With Bleeding - Trimester 2 (Safety Pop.)0.4 DaysStandard Deviation 1.85
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Days With Bleeding - Trimester 2 (Safety Pop.)0.4 DaysStandard Deviation 2.02
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Days With Bleeding - Trimester 2 (Safety Pop.)0.2 DaysStandard Deviation 1.77
PlaceboNumber of Days With Bleeding - Trimester 2 (Safety Pop.)0.1 DaysStandard Deviation 0.42
Secondary

Number of Days With Bleeding - Trimester 3 (Safety Pop.)

Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 3

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 3. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Days With Bleeding - Trimester 3 (Safety Pop.)0.5 DaysStandard Deviation 2.32
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Days With Bleeding - Trimester 3 (Safety Pop.)0.5 DaysStandard Deviation 2.29
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Days With Bleeding - Trimester 3 (Safety Pop.)0.2 DaysStandard Deviation 1.43
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Days With Bleeding - Trimester 3 (Safety Pop.)0.1 DaysStandard Deviation 0.67
PlaceboNumber of Days With Bleeding - Trimester 3 (Safety Pop.)0.0 DaysStandard Deviation 0.1
Secondary

Number of Days With Bleeding - Trimester 4 (Safety Pop.)

Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 4

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 4. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Days With Bleeding - Trimester 4 (Safety Pop.)0.8 DaysStandard Deviation 3.48
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Days With Bleeding - Trimester 4 (Safety Pop.)0.4 DaysStandard Deviation 2.06
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Days With Bleeding - Trimester 4 (Safety Pop.)0.2 DaysStandard Deviation 1.2
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Days With Bleeding - Trimester 4 (Safety Pop.)0.0 DaysStandard Deviation 0.26
PlaceboNumber of Days With Bleeding - Trimester 4 (Safety Pop.)0.1 DaysStandard Deviation 0.43
Secondary

Number of Days With Spotting - Trimester 1 (Safety Pop.)

Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 1

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 1. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Days With Spotting - Trimester 1 (Safety Pop.)3.0 DaysStandard Deviation 8.81
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Days With Spotting - Trimester 1 (Safety Pop.)1.7 DaysStandard Deviation 6.05
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Days With Spotting - Trimester 1 (Safety Pop.)1.3 DaysStandard Deviation 5.08
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Days With Spotting - Trimester 1 (Safety Pop.)0.8 DaysStandard Deviation 2.29
PlaceboNumber of Days With Spotting - Trimester 1 (Safety Pop.)0.6 DaysStandard Deviation 2.63
Secondary

Number of Days With Spotting - Trimester 2 (Safety Pop.)

Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 2

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 2. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Days With Spotting - Trimester 2 (Safety Pop.)2.9 DaysStandard Deviation 8.63
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Days With Spotting - Trimester 2 (Safety Pop.)0.9 DaysStandard Deviation 3.85
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Days With Spotting - Trimester 2 (Safety Pop.)1.5 DaysStandard Deviation 9.16
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Days With Spotting - Trimester 2 (Safety Pop.)0.7 DaysStandard Deviation 4.3
PlaceboNumber of Days With Spotting - Trimester 2 (Safety Pop.)0.1 DaysStandard Deviation 0.74
Secondary

Number of Days With Spotting - Trimester 3 (Safety Pop.)

Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 3

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 3. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Days With Spotting - Trimester 3 (Safety Pop.)2.5 DaysStandard Deviation 8.28
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Days With Spotting - Trimester 3 (Safety Pop.)0.7 DaysStandard Deviation 2.55
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Days With Spotting - Trimester 3 (Safety Pop.)0.9 DaysStandard Deviation 6.04
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Days With Spotting - Trimester 3 (Safety Pop.)0.3 DaysStandard Deviation 1.9
PlaceboNumber of Days With Spotting - Trimester 3 (Safety Pop.)0.0 DaysStandard Deviation 0.14
Secondary

Number of Days With Spotting - Trimester 4 (Safety Pop.)

Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 4

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 4. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Days With Spotting - Trimester 4 (Safety Pop.)1.9 DaysStandard Deviation 7.59
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Days With Spotting - Trimester 4 (Safety Pop.)0.5 DaysStandard Deviation 3.36
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Days With Spotting - Trimester 4 (Safety Pop.)0.8 DaysStandard Deviation 5.75
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Days With Spotting - Trimester 4 (Safety Pop.)0.3 DaysStandard Deviation 1.17
PlaceboNumber of Days With Spotting - Trimester 4 (Safety Pop.)0.1 DaysStandard Deviation 0.67
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 10 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 10 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 10 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 10 to 13222 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 10 to 13271 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 10 to 13273 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 10 to 13248 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 10 to 1385 Participants
p-value: <0.001Fisher Exact
p-value: 0.387Fisher Exact
p-value: 0.215Fisher Exact
p-value: 0.639Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 11 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 11 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 11 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 11 to 13231 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 11 to 13275 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 11 to 13277 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 11 to 13249 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 11 to 1385 Participants
p-value: 0.008Fisher Exact
p-value: 0.643Fisher Exact
p-value: 0.501Fisher Exact
p-value: 1Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 12 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 12 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 12 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 12 to 13238 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 12 to 13278 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 12 to 13278 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 12 to 13252 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 12 to 1386 Participants
p-value: 0.013Fisher Exact
p-value: 0.616Fisher Exact
p-value: 0.352Fisher Exact
p-value: 1Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 1 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 1 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 1 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 1 to 13156 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 1 to 13202 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 1 to 13207 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 1 to 13196 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 1 to 1371 Participants
p-value: <0.001Fisher Exact
p-value: 0.048Fisher Exact
p-value: 0.049Fisher Exact
p-value: 0.328Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 2 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 2 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 2 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 2 to 13166 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 2 to 13220 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 2 to 13215 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 2 to 13212 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 2 to 1374 Participants
p-value: <0.001Fisher Exact
p-value: 0.123Fisher Exact
p-value: 0.03Fisher Exact
p-value: 0.649Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 3 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 3 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 3 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 3 to 13174 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 3 to 13227 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 3 to 13225 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 3 to 13218 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 3 to 1377 Participants
p-value: <0.001Fisher Exact
p-value: 0.059Fisher Exact
p-value: 0.023Fisher Exact
p-value: 0.426Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 4 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 4 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 4 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 4 to 13177 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 4 to 13236 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 4 to 13233 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 4 to 13229 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 4 to 1380 Participants
p-value: <0.001Fisher Exact
p-value: 0.044Fisher Exact
p-value: 0.011Fisher Exact
p-value: 0.481Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 5 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 5 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 5 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 5 to 13183 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 5 to 13244 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 5 to 13240 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 5 to 13234 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 5 to 1380 Participants
p-value: <0.001Fisher Exact
p-value: 0.11Fisher Exact
p-value: 0.045Fisher Exact
p-value: 0.853Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 6 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 6 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 6 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 6 to 13186 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 6 to 13250 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 6 to 13249 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 6 to 13236 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 6 to 1380 Participants
p-value: <0.001Fisher Exact
p-value: 0.245Fisher Exact
p-value: 0.145Fisher Exact
p-value: 1Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 7 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 7 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 7 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 7 to 13200 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 7 to 13253 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 7 to 13255 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 7 to 13238 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 7 to 1382 Participants
p-value: <0.001Fisher Exact
p-value: 0.163Fisher Exact
p-value: 0.091Fisher Exact
p-value: 0.693Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 8 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 8 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 8 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 8 to 13209 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 8 to 13262 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 8 to 13262 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 8 to 13242 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 8 to 1384 Participants
p-value: <0.001Fisher Exact
p-value: 0.178Fisher Exact
p-value: 0.097Fisher Exact
p-value: 0.522Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From Cycle 9 to 13

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 9 to 13 was calculated and compared between active and placebo treatments.

Time frame: Cycle 9 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 9 to 13214 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 9 to 13267 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 9 to 13266 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From Cycle 9 to 13246 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From Cycle 9 to 1384 Participants
p-value: <0.001Fisher Exact
p-value: 0.315Fisher Exact
p-value: 0.181Fisher Exact
p-value: 0.821Fisher Exact
Secondary

Number of Subjects With Cumulative Amenorrhea From the 13th Cycle

Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from the 13th Cycle was calculated and compared between active and placebo treatments.

Time frame: The 13th Cycle

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From the 13th Cycle249 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects With Cumulative Amenorrhea From the 13th Cycle282 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From the 13th Cycle283 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects With Cumulative Amenorrhea From the 13th Cycle254 Participants
PlaceboNumber of Subjects With Cumulative Amenorrhea From the 13th Cycle88 Participants
p-value: 0.023Fisher Exact
p-value: 0.535Fisher Exact
p-value: 0.183Fisher Exact
p-value: 0.738Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 2 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles209 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles256 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles265 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles244 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles84 Participants
p-value: 0Fisher Exact
p-value: 0.069Fisher Exact
p-value: 0.131Fisher Exact
p-value: 0.661Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 3 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles214 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles258 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles267 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles246 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles85 Participants
p-value: 0Fisher Exact
p-value: 0.04Fisher Exact
p-value: 0.082Fisher Exact
p-value: 0.495Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 1 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles204 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles251 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles263 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles239 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles82 Participants
p-value: 0Fisher Exact
p-value: 0.122Fisher Exact
p-value: 0.28Fisher Exact
p-value: 0.692Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 4 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles217 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles261 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles273 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles253 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles86 Participants
p-value: 0Fisher Exact
p-value: 0.032Fisher Exact
p-value: 0.137Fisher Exact
p-value: 0.792Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 5 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles224 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles265 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles278 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles253 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles86 Participants
p-value: 0Fisher Exact
p-value: 0.067Fisher Exact
p-value: 0.26Fisher Exact
p-value: 0.792Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 6 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles227 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles268 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles280 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles256 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles86 Participants
p-value: 0.001Fisher Exact
p-value: 0.095Fisher Exact
p-value: 0.352Fisher Exact
p-value: 1Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 7 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles237 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles271 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles282 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles256 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles87 Participants
p-value: 0.002Fisher Exact
p-value: 0.075Fisher Exact
p-value: 0.225Fisher Exact
p-value: 0.769Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 8 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles242 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles276 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles285 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles258 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles88 Participants
p-value: 0.002Fisher Exact
p-value: 0.084Fisher Exact
p-value: 0.183Fisher Exact
p-value: 0.738Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 9 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles245 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles279 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles288 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles259 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles88 Participants
p-value: 0.006Fisher Exact
p-value: 0.125Fisher Exact
p-value: 0.386Fisher Exact
p-value: 0.737Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 10 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles248 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles281 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles292 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles261 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles88 Participants
p-value: 0.009Fisher Exact
p-value: 0.183Fisher Exact
p-value: 0.745Fisher Exact
p-value: 1Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 11 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles251 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles284 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles294 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles261 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles88 Participants
p-value: 0.035Fisher Exact
p-value: 0.536Fisher Exact
p-value: 1Fisher Exact
p-value: 1Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: Cycle 12 to 13

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles260 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles284 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles295 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles260 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles88 Participants
p-value: 0.261Fisher Exact
p-value: 0.536Fisher Exact
p-value: 1Fisher Exact
p-value: 1Fisher Exact
Secondary

Number of Subjects Without Bleeding for Consecutive Cycles

No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.

Time frame: The 13th Cycle

Population: Subjects who received study drug for at least 1 complete 28-day cycle (at least 23 days in length); subjects who reported bleeding days during a partial cycle are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles268 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgNumber of Subjects Without Bleeding for Consecutive Cycles287 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles296 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgNumber of Subjects Without Bleeding for Consecutive Cycles261 Participants
PlaceboNumber of Subjects Without Bleeding for Consecutive Cycles89 Participants
p-value: 0.463Fisher Exact
p-value: 0.687Fisher Exact
p-value: 1Fisher Exact
p-value: 1Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 10.

Time frame: Baseline and Week 10

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=50% Reduction93 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=75% Reduction73 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=50% Reduction94 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=75% Reduction60 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=50% Reduction92 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=75% Reduction57 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=75% Reduction57 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=50% Reduction93 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=50% Reduction54 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)>=75% Reduction23 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 11.

Time frame: Baseline and Week 11

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=50% Reduction94 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=75% Reduction71 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=50% Reduction97 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=75% Reduction64 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=50% Reduction94 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=75% Reduction52 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=75% Reduction62 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=50% Reduction95 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=50% Reduction55 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)>=75% Reduction26 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: 0.003Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 12.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=50% Reduction97 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=75% Reduction73 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=50% Reduction94 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=75% Reduction64 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=50% Reduction90 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=75% Reduction50 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=75% Reduction58 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=50% Reduction95 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=50% Reduction55 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)>=75% Reduction32 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: 0.056Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: 0.017Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 1.

Time frame: Baseline and Week 1

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=50% Reduction14 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=75% Reduction2 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=50% Reduction10 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=75% Reduction2 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=50% Reduction12 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=75% Reduction1 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=75% Reduction4 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=50% Reduction19 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=50% Reduction10 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)>=75% Reduction1 Participants
Comparison: \>=50% Reductionp-value: 0.523Fisher Exact
Comparison: \>=75% Reductionp-value: 1Fisher Exact
Comparison: \>=50% Reductionp-value: 0.821Fisher Exact
Comparison: \>=75% Reductionp-value: 1Fisher Exact
Comparison: \>=50% Reductionp-value: 0.828Fisher Exact
Comparison: \>=75% Reductionp-value: 1Fisher Exact
Comparison: \>=50% Reductionp-value: 0.239Fisher Exact
Comparison: \>=75% Reductionp-value: 0.377Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 2.

Time frame: Baseline and Week 2

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=50% Reduction36 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=75% Reduction15 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=50% Reduction24 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=75% Reduction7 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=50% Reduction30 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=75% Reduction9 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=75% Reduction17 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=50% Reduction39 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=50% Reduction21 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)>=75% Reduction4 Participants
Comparison: \>=50% Reductionp-value: 0.036Fisher Exact
Comparison: \>=75% Reductionp-value: 0.015Fisher Exact
Comparison: \>=50% Reductionp-value: 1Fisher Exact
Comparison: \>=75% Reductionp-value: 0.546Fisher Exact
Comparison: \>=50% Reductionp-value: 0.352Fisher Exact
Comparison: \>=75% Reductionp-value: 0.261Fisher Exact
Comparison: \>=50% Reductionp-value: 0.058Fisher Exact
Comparison: \>=75% Reductionp-value: 0.011Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 3.

Time frame: Baseline and Week 3

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=50% Reduction63 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=75% Reduction33 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=75% Reduction14 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=50% Reduction49 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=50% Reduction50 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=75% Reduction15 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=50% Reduction61 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=75% Reduction22 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=75% Reduction6 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)>=50% Reduction33 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.115Fisher Exact
Comparison: \>=75% Reductionp-value: 0.11Fisher Exact
Comparison: \>=50% Reductionp-value: 0.089Fisher Exact
Comparison: \>=75% Reductionp-value: 0.074Fisher Exact
Comparison: \>=50% Reductionp-value: 0.011Fisher Exact
Comparison: \>=75% Reductionp-value: 0.008Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 4.

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=50% Reduction80 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=75% Reduction44 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=50% Reduction62 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=75% Reduction28 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=50% Reduction65 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=75% Reduction24 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=75% Reduction33 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=50% Reduction73 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=50% Reduction35 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)>=75% Reduction6 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.011Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.002Fisher Exact
Comparison: \>=75% Reductionp-value: 0.002Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 5.

Time frame: Baseline and Week 5

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=50% Reduction86 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=75% Reduction48 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=50% Reduction72 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=75% Reduction34 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=50% Reduction69 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=75% Reduction27 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=75% Reduction37 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=50% Reduction82 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=50% Reduction47 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)>=75% Reduction13 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.048Fisher Exact
Comparison: \>=75% Reductionp-value: 0.006Fisher Exact
Comparison: \>=50% Reductionp-value: 0.063Fisher Exact
Comparison: \>=75% Reductionp-value: 0.058Fisher Exact
Comparison: \>=50% Reductionp-value: 0.004Fisher Exact
Comparison: \>=75% Reductionp-value: 0.003Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 6.

Time frame: Baseline and Week 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=50% Reduction92 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=75% Reduction61 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=50% Reduction78 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=75% Reduction39 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=50% Reduction76 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=75% Reduction39 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=75% Reduction43 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=50% Reduction83 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=50% Reduction52 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)>=75% Reduction16 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.05Fisher Exact
Comparison: \>=75% Reductionp-value: 0.006Fisher Exact
Comparison: \>=50% Reductionp-value: 0.048Fisher Exact
Comparison: \>=75% Reductionp-value: 0.004Fisher Exact
Comparison: \>=50% Reductionp-value: 0.02Fisher Exact
Comparison: \>=75% Reductionp-value: 0.001Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 7.

Time frame: Baseline and Week 7

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=50% Reduction93 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=75% Reduction63 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=50% Reduction87 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=75% Reduction46 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=50% Reduction81 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=75% Reduction44 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=75% Reduction47 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=50% Reduction95 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=50% Reduction49 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)>=75% Reduction16 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.006Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 8.

Time frame: Baseline and Week 8

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=50% Reduction98 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=75% Reduction64 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=50% Reduction85 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=75% Reduction53 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=50% Reduction90 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=75% Reduction45 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=75% Reduction51 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=50% Reduction93 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=50% Reduction54 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)>=75% Reduction20 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.013Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.001Fisher Exact
Comparison: \>=75% Reductionp-value: 0.004Fisher Exact
Comparison: \>=50% Reductionp-value: 0.003Fisher Exact
Comparison: \>=75% Reductionp-value: 0.001Fisher Exact
Secondary

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 9.

Time frame: Baseline and Week 9

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=50% Reduction95 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=75% Reduction69 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=50% Reduction95 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=75% Reduction63 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=50% Reduction91 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=75% Reduction54 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=75% Reduction56 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=50% Reduction94 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=50% Reduction58 Participants
PlaceboReduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)>=75% Reduction22 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.004Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 10.

Time frame: Baseline and Week 10

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=50% Reduction95 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=75% Reduction78 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=50% Reduction102 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=75% Reduction69 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=50% Reduction100 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=75% Reduction62 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=75% Reduction64 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=50% Reduction101 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=50% Reduction68 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)>=75% Reduction37 Participants
Comparison: \>=50% Reductionp-value: 0.004Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.002Fisher Exact
Comparison: \>=75% Reductionp-value: 0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.001Fisher Exact
Comparison: \>=75% Reductionp-value: 0.009Fisher Exact
Comparison: \>=50% Reductionp-value: 0.018Fisher Exact
Comparison: \>=75% Reductionp-value: 0.021Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 11.

Time frame: Baseline and Week 11

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=50% Reduction95 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=75% Reduction79 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=50% Reduction105 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=75% Reduction74 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=50% Reduction97 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=75% Reduction65 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=75% Reduction68 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=50% Reduction104 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=50% Reduction59 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)>=75% Reduction34 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12.

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=50% Reduction98 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=75% Reduction84 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=50% Reduction104 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=75% Reduction75 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=50% Reduction94 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=75% Reduction66 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=75% Reduction68 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=50% Reduction99 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=50% Reduction67 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)>=75% Reduction37 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.006Fisher Exact
Comparison: \>=75% Reductionp-value: 0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.015Fisher Exact
Comparison: \>=75% Reductionp-value: 0.005Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe VMS from Baseline to Week 1.

Time frame: Baseline and Week 1

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=75% Reduction3 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=50% Reduction15 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=50% Reduction17 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=75% Reduction4 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=75% Reduction4 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=50% Reduction15 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=50% Reduction25 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=75% Reduction5 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=75% Reduction1 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)>=50% Reduction16 Participants
Comparison: \>=50% Reductionp-value: 0.85Fisher Exact
Comparison: \>=75% Reductionp-value: 0.622Fisher Exact
Comparison: \>=50% Reductionp-value: 1Fisher Exact
Comparison: \>=75% Reductionp-value: 0.374Fisher Exact
Comparison: \>=50% Reductionp-value: 0.706Fisher Exact
Comparison: \>=75% Reductionp-value: 0.372Fisher Exact
Comparison: \>=50% Reductionp-value: 0.316Fisher Exact
Comparison: \>=75% Reductionp-value: 0.221Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 2.

Time frame: Baseline and Week 2

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=50% Reduction44 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=75% Reduction21 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=50% Reduction35 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=75% Reduction12 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=50% Reduction34 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=75% Reduction15 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=75% Reduction20 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=50% Reduction49 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=50% Reduction35 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)>=75% Reduction6 Participants
Comparison: \>=50% Reductionp-value: 0.283Fisher Exact
Comparison: \>=75% Reductionp-value: 0.004Fisher Exact
Comparison: \>=50% Reductionp-value: 0.68Fisher Exact
Comparison: \>=75% Reductionp-value: 0.232Fisher Exact
Comparison: \>=50% Reductionp-value: 0.677Fisher Exact
Comparison: \>=75% Reductionp-value: 0.073Fisher Exact
Comparison: \>=50% Reductionp-value: 0.301Fisher Exact
Comparison: \>=75% Reductionp-value: 0.013Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 3.

Time frame: Baseline and Week 3

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=50% Reduction68 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=75% Reduction38 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=50% Reduction59 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=75% Reduction24 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=50% Reduction54 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=75% Reduction21 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=75% Reduction29 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=50% Reduction71 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=50% Reduction42 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)>=75% Reduction15 Participants
Comparison: \>=50% Reductionp-value: 0.003Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.135Fisher Exact
Comparison: \>=75% Reductionp-value: 0.231Fisher Exact
Comparison: \>=50% Reductionp-value: 0.377Fisher Exact
Comparison: \>=75% Reductionp-value: 0.478Fisher Exact
Comparison: \>=50% Reductionp-value: 0.015Fisher Exact
Comparison: \>=75% Reductionp-value: 0.1Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4.

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=50% Reduction82 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=75% Reduction55 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=50% Reduction70 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=75% Reduction34 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=50% Reduction74 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=75% Reduction32 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=75% Reduction45 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=50% Reduction81 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=50% Reduction41 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)>=75% Reduction15 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.009Fisher Exact
Comparison: \>=75% Reductionp-value: 0.017Fisher Exact
p-value: 0.001Fisher Exact
Comparison: \>=75% Reductionp-value: 0.025Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 5.

Time frame: Baseline and Week 5

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=50% Reduction93 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=75% Reduction55 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=50% Reduction80 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=75% Reduction47 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=50% Reduction74 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=75% Reduction38 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=75% Reduction54 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=50% Reduction90 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=50% Reduction55 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)>=75% Reduction27 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.066Fisher Exact
Comparison: \>=75% Reductionp-value: 0.055Fisher Exact
Comparison: \>=50% Reductionp-value: 0.174Fisher Exact
Comparison: \>=75% Reductionp-value: 0.319Fisher Exact
Comparison: \>=50% Reductionp-value: 0.007Fisher Exact
Comparison: \>=75% Reductionp-value: 0.008Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 6.

Time frame: Baseline and Week 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=75% Reduction68 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=50% Reduction98 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=75% Reduction51 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=50% Reduction85 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=75% Reduction47 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=50% Reduction82 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=50% Reduction95 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=75% Reduction56 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=75% Reduction30 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)>=50% Reduction55 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.019Fisher Exact
Comparison: \>=75% Reductionp-value: 0.061Fisher Exact
Comparison: \>=50% Reductionp-value: 0.026Fisher Exact
Comparison: \>=75% Reductionp-value: 0.104Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: 0.018Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 7.

Time frame: Baseline and Week 7

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=50% Reduction96 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=75% Reduction71 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=50% Reduction93 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=75% Reduction63 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=50% Reduction88 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=75% Reduction56 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=75% Reduction58 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=50% Reduction101 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=50% Reduction58 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)>=75% Reduction32 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.006Fisher Exact
Comparison: \>=75% Reductionp-value: 0.003Fisher Exact
Comparison: \>=50% Reductionp-value: 0.017Fisher Exact
Comparison: \>=75% Reductionp-value: 0.025Fisher Exact
Comparison: \>=50% Reductionp-value: 0.001Fisher Exact
Comparison: \>=75% Reductionp-value: 0.037Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8.

Time frame: Baseline and Week 8

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=50% Reduction102 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=75% Reduction78 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=50% Reduction98 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=75% Reduction64 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=50% Reduction90 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=75% Reduction59 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=75% Reduction62 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=50% Reduction100 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=50% Reduction60 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)>=75% Reduction37 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.001Fisher Exact
Comparison: \>=75% Reductionp-value: 0.016Fisher Exact
Comparison: \>=50% Reductionp-value: 0.012Fisher Exact
Comparison: \>=75% Reductionp-value: 0.053Fisher Exact
Comparison: \>=50% Reductionp-value: 0.004Fisher Exact
Comparison: \>=75% Reductionp-value: 0.074Fisher Exact
Secondary

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 9.

Time frame: Baseline and Week 9

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=50% Reduction98 Participants
Combined Estradiol 1 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=75% Reduction72 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=50% Reduction107 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=75% Reduction73 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=50% Reduction92 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=75% Reduction63 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=75% Reduction63 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=50% Reduction101 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=50% Reduction63 Participants
PlaceboReduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)>=75% Reduction35 Participants
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: <0.001Fisher Exact
Comparison: \>=75% Reductionp-value: <0.001Fisher Exact
Comparison: \>=50% Reductionp-value: 0.009Fisher Exact
Comparison: \>=75% Reductionp-value: 0.004Fisher Exact
Comparison: \>=50% Reductionp-value: 0.002Fisher Exact
Comparison: \>=75% Reductionp-value: 0.015Fisher Exact
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 10

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-0.87 scores on a scaleStandard Deviation 0.97
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-0.58 scores on a scaleStandard Deviation 0.731
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-0.57 scores on a scaleStandard Deviation 0.785
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-0.45 scores on a scaleStandard Deviation 0.754
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-0.35 scores on a scaleStandard Deviation 0.557
p-value: <0.00195% CI: [-0.71, -0.33]Mixed Models Analysis
p-value: 0.00795% CI: [-0.44, -0.07]Mixed Models Analysis
p-value: 0.03895% CI: [-0.39, -0.01]Mixed Models Analysis
p-value: 0.28395% CI: [-0.29, 0.08]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 11

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-0.86 scores on a scaleStandard Deviation 0.95
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-0.67 scores on a scaleStandard Deviation 0.788
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-0.56 scores on a scaleStandard Deviation 0.8
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-0.50 scores on a scaleStandard Deviation 0.776
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-0.36 scores on a scaleStandard Deviation 0.543
p-value: <0.00195% CI: [-0.72, -0.34]Mixed Models Analysis
p-value: <0.00195% CI: [-0.54, -0.16]Mixed Models Analysis
p-value: 0.02795% CI: [-0.41, -0.02]Mixed Models Analysis
p-value: 0.07195% CI: [-0.36, 0.01]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-0.94 scores on a scaleStandard Deviation 0.986
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-0.71 scores on a scaleStandard Deviation 0.784
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-0.54 scores on a scaleStandard Deviation 0.761
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-0.54 scores on a scaleStandard Deviation 0.824
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-0.39 scores on a scaleStandard Deviation 0.585
p-value: <0.00195% CI: [-0.77, -0.37]Mixed Models Analysis
p-value: <0.00195% CI: [-0.57, -0.18]Mixed Models Analysis
p-value: 0.03995% CI: [-0.4, -0.01]Mixed Models Analysis
p-value: 0.08895% CI: [-0.36, 0.03]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 1

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.06 scores on a scaleStandard Deviation 0.211
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.05 scores on a scaleStandard Deviation 0.206
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.02 scores on a scaleStandard Deviation 0.197
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.08 scores on a scaleStandard Deviation 0.305
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.07 scores on a scaleStandard Deviation 0.2
p-value: 0.67695% CI: [-0.04, 0.07]Mixed Models Analysis
p-value: 0.43695% CI: [-0.03, 0.07]Mixed Models Analysis
p-value: 0.10695% CI: [-0.01, 0.1]Mixed Models Analysis
p-value: 0.75295% CI: [-0.06, 0.04]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 2

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.16 scores on a scaleStandard Deviation 0.349
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.14 scores on a scaleStandard Deviation 0.342
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.06 scores on a scaleStandard Deviation 0.309
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.12 scores on a scaleStandard Deviation 0.288
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.11 scores on a scaleStandard Deviation 0.275
p-value: 0.19395% CI: [-0.12, 0.02]Mixed Models Analysis
p-value: 0.31995% CI: [-0.11, 0.04]Mixed Models Analysis
p-value: 0.23995% CI: [-0.03, 0.12]Mixed Models Analysis
p-value: 0.7295% CI: [-0.09, 0.06]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 3

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.25 scores on a scaleStandard Deviation 0.48
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.24 scores on a scaleStandard Deviation 0.402
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.11 scores on a scaleStandard Deviation 0.379
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.20 scores on a scaleStandard Deviation 0.412
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.15 scores on a scaleStandard Deviation 0.35
p-value: 0.0395% CI: [-0.2, -0.01]Mixed Models Analysis
p-value: 0.0695% CI: [-0.19, 0]Mixed Models Analysis
p-value: 0.50695% CI: [-0.06, 0.13]Mixed Models Analysis
p-value: 0.23295% CI: [-0.15, 0.04]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.31 scores on a scaleStandard Deviation 0.527
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.31 scores on a scaleStandard Deviation 0.54
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.19 scores on a scaleStandard Deviation 0.434
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.27 scores on a scaleStandard Deviation 0.507
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.17 scores on a scaleStandard Deviation 0.368
p-value: 0.02795% CI: [-0.24, -0.01]Mixed Models Analysis
p-value: 0.01195% CI: [-0.26, -0.03]Mixed Models Analysis
p-value: 0.7195% CI: [-0.13, 0.09]Mixed Models Analysis
p-value: 0.07295% CI: [-0.21, 0.01]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 5

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.46 scores on a scaleStandard Deviation 0.68
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.37 scores on a scaleStandard Deviation 0.546
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.23 scores on a scaleStandard Deviation 0.441
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.36 scores on a scaleStandard Deviation 0.619
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.24 scores on a scaleStandard Deviation 0.524
p-value: <0.00195% CI: [-0.36, -0.09]Mixed Models Analysis
p-value: 0.06295% CI: [-0.26, 0.01]Mixed Models Analysis
p-value: 0.88695% CI: [-0.12, 0.14]Mixed Models Analysis
p-value: 0.06795% CI: [-0.26, 0.01]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.62 scores on a scaleStandard Deviation 0.835
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.42 scores on a scaleStandard Deviation 0.627
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.33 scores on a scaleStandard Deviation 0.588
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.46 scores on a scaleStandard Deviation 0.775
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.27 scores on a scaleStandard Deviation 0.548
p-value: <0.00195% CI: [-0.53, -0.2]Mixed Models Analysis
p-value: 0.05395% CI: [-0.32, 0]Mixed Models Analysis
p-value: 0.41395% CI: [-0.23, 0.09]Mixed Models Analysis
p-value: 0.01895% CI: [-0.35, -0.03]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 7

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.65 scores on a scaleStandard Deviation 0.798
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.50 scores on a scaleStandard Deviation 0.687
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.42 scores on a scaleStandard Deviation 0.66
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.47 scores on a scaleStandard Deviation 0.773
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.27 scores on a scaleStandard Deviation 0.469
p-value: <0.00195% CI: [-0.54, -0.2]Mixed Models Analysis
p-value: 0.00695% CI: [-0.4, -0.07]Mixed Models Analysis
p-value: 0.07295% CI: [-0.32, 0.01]Mixed Models Analysis
p-value: 0.01495% CI: [-0.37, -0.04]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 8

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.70 scores on a scaleStandard Deviation 0.858
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.51 scores on a scaleStandard Deviation 0.633
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.44 scores on a scaleStandard Deviation 0.701
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.47 scores on a scaleStandard Deviation 0.75
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.33 scores on a scaleStandard Deviation 0.545
p-value: <0.00195% CI: [-0.55, -0.21]Mixed Models Analysis
p-value: 0.01695% CI: [-0.37, -0.04]Mixed Models Analysis
p-value: 0.16995% CI: [-0.29, 0.05]Mixed Models Analysis
p-value: 0.08195% CI: [-0.31, 0.02]Mixed Models Analysis
Secondary

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 9

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.78 scores on a scaleStandard Deviation 0.909
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.55 scores on a scaleStandard Deviation 0.708
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.51 scores on a scaleStandard Deviation 0.735
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.54 scores on a scaleStandard Deviation 0.78
PlaceboSeverity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.31 scores on a scaleStandard Deviation 0.515
p-value: <0.00195% CI: [-0.66, -0.3]Mixed Models Analysis
p-value: 0.00395% CI: [-0.45, -0.1]Mixed Models Analysis
p-value: 0.02295% CI: [-0.39, -0.03]Mixed Models Analysis
p-value: 0.00695% CI: [-0.43, -0.07]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 10

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-1.05 scores on a scaleStandard Deviation 0.953
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-0.77 scores on a scaleStandard Deviation 0.727
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-0.78 scores on a scaleStandard Deviation 0.769
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-0.62 scores on a scaleStandard Deviation 0.739
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)-0.53 scores on a scaleStandard Deviation 0.575
p-value: <0.00195% CI: [-0.71, -0.33]Mixed Models Analysis
p-value: 0.00395% CI: [-0.46, -0.09]Mixed Models Analysis
p-value: 0.01695% CI: [-0.41, -0.04]Mixed Models Analysis
p-value: 0.3195% CI: [-0.28, 0.09]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 11

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-1.04 scores on a scaleStandard Deviation 0.931
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-0.86 scores on a scaleStandard Deviation 0.777
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-0.78 scores on a scaleStandard Deviation 0.782
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-0.68 scores on a scaleStandard Deviation 0.767
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)-0.54 scores on a scaleStandard Deviation 0.566
p-value: <0.00195% CI: [-0.72, -0.34]Mixed Models Analysis
p-value: <0.00195% CI: [-0.56, -0.19]Mixed Models Analysis
p-value: 0.01195% CI: [-0.44, -0.06]Mixed Models Analysis
p-value: 0.07695% CI: [-0.36, 0.02]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 12

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-1.12 scores on a scaleStandard Deviation 0.963
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-0.90 scores on a scaleStandard Deviation 0.783
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-0.76 scores on a scaleStandard Deviation 0.744
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-0.71 scores on a scaleStandard Deviation 0.806
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)-0.56 scores on a scaleStandard Deviation 0.603
p-value: <0.00195% CI: [-0.77, -0.38]Mixed Models Analysis
p-value: <0.00195% CI: [-0.59, -0.2]Mixed Models Analysis
p-value: 0.01895% CI: [-0.43, -0.04]Mixed Models Analysis
p-value: 0.09695% CI: [-0.36, 0.03]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 1

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.24 scores on a scaleStandard Deviation 0.305
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.25 scores on a scaleStandard Deviation 0.27
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.23 scores on a scaleStandard Deviation 0.264
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.25 scores on a scaleStandard Deviation 0.327
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)-0.25 scores on a scaleStandard Deviation 0.257
p-value: 0.92895% CI: [-0.07, 0.06]Mixed Models Analysis
p-value: 0.80195% CI: [-0.06, 0.08]Mixed Models Analysis
p-value: 0.99195% CI: [-0.07, 0.07]Mixed Models Analysis
p-value: 0.64295% CI: [-0.05, 0.08]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 2

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.34 scores on a scaleStandard Deviation 0.411
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.34 scores on a scaleStandard Deviation 0.39
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.27 scores on a scaleStandard Deviation 0.354
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.29 scores on a scaleStandard Deviation 0.314
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)-0.28 scores on a scaleStandard Deviation 0.31
p-value: 0.23195% CI: [-0.14, 0.03]Mixed Models Analysis
p-value: 0.17395% CI: [-0.14, 0.03]Mixed Models Analysis
p-value: 0.71795% CI: [-0.07, 0.1]Mixed Models Analysis
p-value: 0.84995% CI: [-0.09, 0.07]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 3

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.43 scores on a scaleStandard Deviation 0.514
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.44 scores on a scaleStandard Deviation 0.437
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.32 scores on a scaleStandard Deviation 0.41
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.37 scores on a scaleStandard Deviation 0.424
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)-0.32 scores on a scaleStandard Deviation 0.372
p-value: 0.03995% CI: [-0.21, -0.01]Mixed Models Analysis
p-value: 0.0395% CI: [-0.21, -0.01]Mixed Models Analysis
p-value: 0.94695% CI: [-0.1, 0.1]Mixed Models Analysis
p-value: 0.30995% CI: [-0.15, 0.05]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 4

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.48 scores on a scaleStandard Deviation 0.547
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.51 scores on a scaleStandard Deviation 0.563
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.40 scores on a scaleStandard Deviation 0.469
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.44 scores on a scaleStandard Deviation 0.514
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)-0.34 scores on a scaleStandard Deviation 0.386
p-value: 0.03195% CI: [-0.25, -0.01]Mixed Models Analysis
p-value: 0.00595% CI: [-0.28, -0.05]Mixed Models Analysis
p-value: 0.40195% CI: [-0.17, 0.07]Mixed Models Analysis
p-value: 0.195% CI: [-0.21, 0.02]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 5

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.64 scores on a scaleStandard Deviation 0.702
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.56 scores on a scaleStandard Deviation 0.558
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.44 scores on a scaleStandard Deviation 0.463
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.53 scores on a scaleStandard Deviation 0.61
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)-0.42 scores on a scaleStandard Deviation 0.551
p-value: 0.00195% CI: [-0.37, -0.09]Mixed Models Analysis
p-value: 0.03495% CI: [-0.28, -0.01]Mixed Models Analysis
p-value: 0.7995% CI: [-0.16, 0.12]Mixed Models Analysis
p-value: 0.08695% CI: [-0.25, 0.02]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 6

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.80 scores on a scaleStandard Deviation 0.84
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.61 scores on a scaleStandard Deviation 0.64
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.54 scores on a scaleStandard Deviation 0.578
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.63 scores on a scaleStandard Deviation 0.763
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)-0.45 scores on a scaleStandard Deviation 0.573
p-value: <0.00195% CI: [-0.53, -0.2]Mixed Models Analysis
p-value: 0.0395% CI: [-0.34, -0.02]Mixed Models Analysis
p-value: 0.24795% CI: [-0.26, 0.07]Mixed Models Analysis
p-value: 0.02295% CI: [-0.35, -0.03]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 7

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.81 scores on a scaleStandard Deviation 0.793
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.69 scores on a scaleStandard Deviation 0.694
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.63 scores on a scaleStandard Deviation 0.637
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.64 scores on a scaleStandard Deviation 0.764
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)-0.44 scores on a scaleStandard Deviation 0.483
p-value: <0.00195% CI: [-0.54, -0.2]Mixed Models Analysis
p-value: 0.00295% CI: [-0.42, -0.09]Mixed Models Analysis
p-value: 0.03195% CI: [-0.34, -0.02]Mixed Models Analysis
p-value: 0.01695% CI: [-0.36, -0.04]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 8

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.88 scores on a scaleStandard Deviation 0.854
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.70 scores on a scaleStandard Deviation 0.642
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.65 scores on a scaleStandard Deviation 0.685
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.64 scores on a scaleStandard Deviation 0.745
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)-0.51 scores on a scaleStandard Deviation 0.563
p-value: <0.00195% CI: [-0.55, -0.21]Mixed Models Analysis
p-value: 0.00895% CI: [-0.4, -0.06]Mixed Models Analysis
p-value: 0.08795% CI: [-0.32, 0.02]Mixed Models Analysis
p-value: 0.09295% CI: [-0.31, 0.02]Mixed Models Analysis
Secondary

Severity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = \[(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3\] / (total number of mild, moderate and severe hot flushes over 7 days).

Time frame: Baseline and Week 9

Population: Randomized to the VMS Substudy, taken one dose of IP, and had at least 5 days of VMS diary data for baseline measurement of freq. \& severity of moderate to severe hot flushes, and had at least 4 days of VMS diary data for 1 on-treatment week of reporting freq. \& severity of hot flushes following initiation of IP.

ArmMeasureValue (MEAN)Dispersion
Combined Estradiol 1 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.96 scores on a scaleStandard Deviation 0.892
Combined Estradiol 0.5 mg / Progesterone 100 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.74 scores on a scaleStandard Deviation 0.699
Combined Estradiol 0.5 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.73 scores on a scaleStandard Deviation 0.72
Combined Estradiol 0.25 mg / Progesterone 50 mgSeverity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.71 scores on a scaleStandard Deviation 0.772
PlaceboSeverity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)-0.48 scores on a scaleStandard Deviation 0.536
p-value: <0.00195% CI: [-0.66, -0.3]Mixed Models Analysis
p-value: 0.00195% CI: [-0.47, -0.12]Mixed Models Analysis
p-value: 0.00995% CI: [-0.42, -0.06]Mixed Models Analysis
p-value: 0.00795% CI: [-0.42, -0.07]Mixed Models Analysis
Secondary

Subject Incidence With Bleeding - Trimester 1 (Safety Pop.)

Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 1

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 1. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgSubject Incidence With Bleeding - Trimester 1 (Safety Pop.)48 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgSubject Incidence With Bleeding - Trimester 1 (Safety Pop.)29 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgSubject Incidence With Bleeding - Trimester 1 (Safety Pop.)25 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgSubject Incidence With Bleeding - Trimester 1 (Safety Pop.)24 Participants
PlaceboSubject Incidence With Bleeding - Trimester 1 (Safety Pop.)4 Participants
p-value: 0.002Fisher Exact
p-value: 0.135Fisher Exact
p-value: 0.26Fisher Exact
p-value: 0.257Fisher Exact
Secondary

Subject Incidence With Bleeding - Trimester 2 (Safety Pop.)

Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 2

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 2. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgSubject Incidence With Bleeding - Trimester 2 (Safety Pop.)45 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgSubject Incidence With Bleeding - Trimester 2 (Safety Pop.)23 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgSubject Incidence With Bleeding - Trimester 2 (Safety Pop.)19 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgSubject Incidence With Bleeding - Trimester 2 (Safety Pop.)5 Participants
PlaceboSubject Incidence With Bleeding - Trimester 2 (Safety Pop.)2 Participants
p-value: <0.001Fisher Exact
p-value: 0.085Fisher Exact
p-value: 0.184Fisher Exact
p-value: 0.681Fisher Exact
Secondary

Subject Incidence With Bleeding - Trimester 3 (Safety Pop.)

Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 3

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 3. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgSubject Incidence With Bleeding - Trimester 3 (Safety Pop.)25 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgSubject Incidence With Bleeding - Trimester 3 (Safety Pop.)21 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgSubject Incidence With Bleeding - Trimester 3 (Safety Pop.)16 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgSubject Incidence With Bleeding - Trimester 3 (Safety Pop.)7 Participants
PlaceboSubject Incidence With Bleeding - Trimester 3 (Safety Pop.)1 Participants
p-value: 0.008Fisher Exact
p-value: 0.036Fisher Exact
p-value: 0.138Fisher Exact
p-value: 0.685Fisher Exact
Secondary

Subject Incidence With Bleeding - Trimester 4 (Safety Pop.)

Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 4

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 4. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgSubject Incidence With Bleeding - Trimester 4 (Safety Pop.)27 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgSubject Incidence With Bleeding - Trimester 4 (Safety Pop.)16 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgSubject Incidence With Bleeding - Trimester 4 (Safety Pop.)9 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgSubject Incidence With Bleeding - Trimester 4 (Safety Pop.)5 Participants
PlaceboSubject Incidence With Bleeding - Trimester 4 (Safety Pop.)2 Participants
p-value: 0.023Fisher Exact
p-value: 0.265Fisher Exact
p-value: 1Fisher Exact
p-value: 1Fisher Exact
Secondary

Subject Incidence With Spotting - Trimester 1 (Safety Pop.)

Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 1

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 1. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgSubject Incidence With Spotting - Trimester 1 (Safety Pop.)90 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgSubject Incidence With Spotting - Trimester 1 (Safety Pop.)74 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgSubject Incidence With Spotting - Trimester 1 (Safety Pop.)68 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgSubject Incidence With Spotting - Trimester 1 (Safety Pop.)58 Participants
PlaceboSubject Incidence With Spotting - Trimester 1 (Safety Pop.)10 Participants
p-value: <0.001Fisher Exact
p-value: 0.004Fisher Exact
p-value: 0.012Fisher Exact
p-value: 0.032Fisher Exact
Secondary

Subject Incidence With Spotting - Trimester 2 (Safety Pop.)

Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 2

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 2. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgSubject Incidence With Spotting - Trimester 2 (Safety Pop.)76 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgSubject Incidence With Spotting - Trimester 2 (Safety Pop.)40 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgSubject Incidence With Spotting - Trimester 2 (Safety Pop.)48 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgSubject Incidence With Spotting - Trimester 2 (Safety Pop.)24 Participants
PlaceboSubject Incidence With Spotting - Trimester 2 (Safety Pop.)4 Participants
p-value: <0.001Fisher Exact
p-value: 0.022Fisher Exact
p-value: 0.004Fisher Exact
p-value: 0.256Fisher Exact
Secondary

Subject Incidence With Spotting - Trimester 3 (Safety Pop.)

Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 3

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 3. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgSubject Incidence With Spotting - Trimester 3 (Safety Pop.)54 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgSubject Incidence With Spotting - Trimester 3 (Safety Pop.)33 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgSubject Incidence With Spotting - Trimester 3 (Safety Pop.)29 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgSubject Incidence With Spotting - Trimester 3 (Safety Pop.)18 Participants
PlaceboSubject Incidence With Spotting - Trimester 3 (Safety Pop.)2 Participants
p-value: <0.001Fisher Exact
p-value: 0.006Fisher Exact
p-value: 0.025Fisher Exact
p-value: 0.182Fisher Exact
Secondary

Subject Incidence With Spotting - Trimester 4 (Safety Pop.)

Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.

Time frame: Trimester 4

Population: Subjects who had taken at least one dose (2 capsules) of IP and had at least one bleeding/spotting diary entry for Trimester 4. Subjects who reported bleeding/spotting diary only for partial trimester are also included.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Combined Estradiol 1 mg / Progesterone 100 mgSubject Incidence With Spotting - Trimester 4 (Safety Pop.)47 Participants
Combined Estradiol 0.5 mg / Progesterone 100 mgSubject Incidence With Spotting - Trimester 4 (Safety Pop.)21 Participants
Combined Estradiol 0.5 mg / Progesterone 50 mgSubject Incidence With Spotting - Trimester 4 (Safety Pop.)27 Participants
Combined Estradiol 0.25 mg / Progesterone 50 mgSubject Incidence With Spotting - Trimester 4 (Safety Pop.)18 Participants
PlaceboSubject Incidence With Spotting - Trimester 4 (Safety Pop.)4 Participants
p-value: 0.002Fisher Exact
p-value: 0.469Fisher Exact
p-value: 0.188Fisher Exact
p-value: 0.613Fisher Exact

Source: ClinicalTrials.gov · Data processed: Mar 2, 2026