Hot Flashes, Menopause, Vasomotor Disturbance
Conditions
Keywords
Menopause, Vasomotor, Symptoms, Estradiol, Venlafaxine
Brief summary
The primary objective of this study is to determine the efficacy of both low-dose oral (by mouth) 17-ß-estradiol and the non-hormonal drug venlafaxine XR compared to placebo in reducing hot flashes. Included in this objective is the intention to compare venlafaxine XR to estradiol therapy, to provide evidence of the relative efficacy of venlafaxine to what is currently considered the most established but also a controversial therapy. 17-ß-estradiol is a type of estrogen. Venlafaxine XR is the extended release (XR) version of venlafaxine. Venlafaxine XR is an serotonin-norepinephrine reuptake inhibitor (SNRI). A placebo is a substance containing no medication.
Detailed description
The MsFLASH-03 study (Menopausal Strategies: Finding Lasting Answers for Symptoms and Health - 03), Comparative Efficacy of Low-Dose Estradiol and the SNRI Venlafaxine XR for Treatment of Menopausal Symptoms, is a randomized, double-blind, placebo-controlled, three arm clinical trial. The design includes: 3 weeks of daily recording of hot flashes prior to drug treatment; 8 weeks of double-blind treatment with oral estradiol, venlafaxine, or placebo; followed by 14 days of drug taper for those on venlafaxine and 14 days of progesterone treatment for those on estradiol; followed by 2 weeks with no treatment for all groups; and a telephone follow-up post-treatment.
Interventions
DRUGLow-dose 17-ß-estradiol with progesterone taper
Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably. The 8 week estradiol treatment is followed by 14 days (2 weeks) of progesterone taper (as medroxy-progesterone 10 mg/day).
DRUGVenlafaxine XR
Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
DRUGPlacebo
The placebo is an inactive pill that looks like the active medication.
Sponsors
National Institute on Aging (NIA)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Complementary and Integrative Health (NCCIH)
Office of Research on Women's Health (ORWH)
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 62 Years
Healthy volunteers
Yes
Inclusion criteria
* Females aged 40-62 years * Postmenopausal or perimenopausal * Having bothersome hot flashes * In general good health * Signed informed consent
Exclusion criteria
* Recent use of systemic hormone therapy or hormonal contraceptives * Recent use of any prescribed, over-the-counter or herbal therapies that are taken specifically for hot flashes * Recent use of selective estrogen receptor modulators (SERMS) or aromatase inhibitors * Recent use of psychotropic medications, including SSRIs (selective serotonin reuptake inhibitors), serotonin-norepinephrine reuptake inhibitors (SNRIs), MAOIs (monoamine oxidase inhibitors), and other antidepressants and anxiolytics. * Known hypersensitivity or contraindications (reasons not to take) to venlafaxine, estrogen, or progestins * Not using a medically approved method of birth control, if sexually active and not 12 or more months since last menstrual period * Recent drug or alcohol abuse * Lifetime diagnosis of psychosis or bipolar disorder * Suicide attempt in the past 3 years or any current suicidal ideation * Current major depression (assessed during screening) * Pregnancy, intending pregnancy, or breast feeding * History of: * Pre-breast cancer or high-risk breast cancer condition * Abnormal bleeding suggestive of endometrial pre-cancer or endometrial hyperplasia * Asthma, diabetes mellitus, epilepsy, and migraine disorders that are not stable or under medical management * Abnormal screening blood tests * Current participation in another drug trial or intervention study * Inability or unwillingness to complete the study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4 | Week 4 | Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 4 study assessment to produce a mean daily frequency for week 4. |
| Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8 | Week 8 | Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 8 study assessment to produce a mean daily frequency for week 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bothersomeness of Hot Flashes -- Week 4 | Week 4 | Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 4. |
| Bothersomeness of Hot Flashes -- Week 8 | Week 8 | Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 8. |
| Severity of Hot Flashes -- Week 4 | Week 4 | Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS severity for week 4. |
| Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8 | Week 8 | The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference. |
| Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4 | Week 4 | The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference. |
| Severity of Hot Flashes -- Week 8 | Week 8 | Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS severity for week 8. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low-dose 17-ß-estradiol With Progesterone Taper Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably. | 97 |
| Venlafaxine XR Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks). | 96 |
| Placebo Placebo: The placebo is an inactive pill that looks like the active medication. | 146 |
| Total | 339 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not provide hot flash diary data | 1 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Low-dose 17-ß-estradiol With Progesterone Taper | Venlafaxine XR | Placebo |
|---|---|---|---|---|
| Age at starting vasomotor symptoms (VMS), years of age < 50 | 171 participants | 47 participants | 51 participants | 73 participants |
| Age at starting vasomotor symptoms (VMS), years of age >= 50 | 163 participants | 48 participants | 44 participants | 71 participants |
| Age at starting vasomotor symptoms (VMS), years of age Missing | 5 participants | 2 participants | 1 participants | 2 participants |
| Age, Continuous | 54.6 years STANDARD_DEVIATION 3.8 | 54.9 years STANDARD_DEVIATION 4.1 | 54.8 years STANDARD_DEVIATION 3.7 | 54.3 years STANDARD_DEVIATION 3.8 |
| Alcohol use (drinks/week) <7 | 265 participants | 71 participants | 77 participants | 117 participants |
| Alcohol use (drinks/week) >=7 | 61 participants | 21 participants | 13 participants | 27 participants |
| Alcohol use (drinks/week) Missing | 13 participants | 5 participants | 6 participants | 2 participants |
| Body Mass Index (BMI) | 28.3 kg/m^2 STANDARD_DEVIATION 6.8 | 28.5 kg/m^2 STANDARD_DEVIATION 6.5 | 29.3 kg/m^2 STANDARD_DEVIATION 6.9 | 27.6 kg/m^2 STANDARD_DEVIATION 6.8 |
| Bothersomeness of Hot Flashes | 2.0 units on a scale STANDARD_DEVIATION 0.5 | 2.1 units on a scale STANDARD_DEVIATION 0.5 | 2.0 units on a scale STANDARD_DEVIATION 0.5 | 2.0 units on a scale STANDARD_DEVIATION 0.5 |
| Education <College graduate | 166 participants | 48 participants | 48 participants | 70 participants |
| Education College graduate | 172 participants | 49 participants | 48 participants | 75 participants |
| Education Missing | 1 participants | 0 participants | 0 participants | 1 participants |
| Generalized Anxiety Disorder 7 (GAD-7) Score Mild anxiety (5 - 9) | 51 participants | 15 participants | 17 participants | 19 participants |
| Generalized Anxiety Disorder 7 (GAD-7) Score Moderate anxiety (>= 10) | 23 participants | 9 participants | 3 participants | 11 participants |
| Generalized Anxiety Disorder 7 (GAD-7) Score No anxiety (0 - 4) | 265 participants | 73 participants | 76 participants | 116 participants |
| Generalized Anxiety Disorder 7 (GAD-7) Score | 2.5 units on a scale STANDARD_DEVIATION 3.6 | 3.0 units on a scale STANDARD_DEVIATION 4.3 | 2.2 units on a scale STANDARD_DEVIATION 3 | 2.4 units on a scale STANDARD_DEVIATION 3.4 |
| Insomnia Severity Index (ISI) Score Clinical insomnia (moderate, 15 - 21) | 78 participants | 21 participants | 25 participants | 32 participants |
| Insomnia Severity Index (ISI) Score Clinical insomnia (severe, >= 22) | 14 participants | 5 participants | 5 participants | 4 participants |
| Insomnia Severity Index (ISI) Score Missing | 8 participants | 3 participants | 1 participants | 4 participants |
| Insomnia Severity Index (ISI) Score No clinically significant insomnia (<= 7) | 106 participants | 28 participants | 26 participants | 52 participants |
| Insomnia Severity Index (ISI) Score Subthreshold insomnia (8 - 14) | 133 participants | 40 participants | 39 participants | 54 participants |
| Insomnia Severity Index (ISI) Score | 11.0 units on a scale STANDARD_DEVIATION 6 | 11.0 units on a scale STANDARD_DEVIATION 6.3 | 11.7 units on a scale STANDARD_DEVIATION 6 | 10.4 units on a scale STANDARD_DEVIATION 5.8 |
| Marital status Married / living with partner | 210 participants | 58 participants | 56 participants | 96 participants |
| Marital status Missing | 2 participants | 1 participants | 0 participants | 1 participants |
| Marital status Never married / Divorced / Widowed | 127 participants | 38 participants | 40 participants | 49 participants |
| Menopause status Indeterminate | 31 participants | 9 participants | 8 participants | 14 participants |
| Menopause status Perimenopausal | 52 participants | 14 participants | 16 participants | 22 participants |
| Menopause status Postmenopausal | 256 participants | 74 participants | 72 participants | 110 participants |
| Patient Health Questionnaire (PHQ-9) Depression Score | 3.4 units on a scale STANDARD_DEVIATION 3.7 | 3.9 units on a scale STANDARD_DEVIATION 4.4 | 3.0 units on a scale STANDARD_DEVIATION 2.9 | 3.4 units on a scale STANDARD_DEVIATION 3.7 |
| Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) | 35.1 units on a scale STANDARD_DEVIATION 22.6 | 36.9 units on a scale STANDARD_DEVIATION 23.8 | 36.8 units on a scale STANDARD_DEVIATION 23.4 | 32.8 units on a scale STANDARD_DEVIATION 21.3 |
| PHQ-9 Depression Score Mild depression (5 - 9) | 64 participants | 18 participants | 23 participants | 23 participants |
| PHQ-9 Depression Score Moderate depression (>= 10) | 29 participants | 11 participants | 3 participants | 15 participants |
| PHQ-9 Depression Score No depression (0 - 4) | 246 participants | 68 participants | 70 participants | 108 participants |
| Pittsburgh Sleep Quality Index (PSQI) Score Good quality sleep (< 5) | 67 participants | 23 participants | 14 participants | 30 participants |
| Pittsburgh Sleep Quality Index (PSQI) Score Missing | 19 participants | 7 participants | 7 participants | 5 participants |
| Pittsburgh Sleep Quality Index (PSQI) Score Moderate sleep quality (5 - < 8) | 102 participants | 21 participants | 35 participants | 46 participants |
| Pittsburgh Sleep Quality Index (PSQI) Score Poor sleep quality (>= 8) | 151 participants | 46 participants | 40 participants | 65 participants |
| Pittsburgh Sleep Quality Index (PSQI) Score | 7.5 units on a scale STANDARD_DEVIATION 3.4 | 7.6 units on a scale STANDARD_DEVIATION 3.6 | 7.6 units on a scale STANDARD_DEVIATION 3.2 | 7.3 units on a scale STANDARD_DEVIATION 3.5 |
| Region of Enrollment United States | 339 participants | 97 participants | 96 participants | 146 participants |
| Severity of Hot Flashes | 1.0 units on a scale STANDARD_DEVIATION 0.5 | 1.1 units on a scale STANDARD_DEVIATION 0.5 | 1.0 units on a scale STANDARD_DEVIATION 0.5 | 1.0 units on a scale STANDARD_DEVIATION 0.4 |
| Sex: Female, Male Female | 339 Participants | 97 Participants | 96 Participants | 146 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Smoking Current | 55 participants | 17 participants | 14 participants | 24 participants |
| Smoking Missing | 3 participants | 0 participants | 1 participants | 2 participants |
| Smoking Never | 174 participants | 50 participants | 54 participants | 70 participants |
| Smoking Past | 107 participants | 30 participants | 27 participants | 50 participants |
| Vasomotor Symptoms (VMS) as number of hot flashes | 8.1 Number of hot flashes per day STANDARD_DEVIATION 5.3 | 8.5 Number of hot flashes per day STANDARD_DEVIATION 5.7 | 8.2 Number of hot flashes per day STANDARD_DEVIATION 5.5 | 7.7 Number of hot flashes per day STANDARD_DEVIATION 4.8 |
| Vasomotor symptom (VMS) number of participants with number of hot flashes / day >= 12 | 53 participants | 18 participants | 14 participants | 21 participants |
| Vasomotor symptom (VMS) number of participants with number of hot flashes / day < 6 | 139 participants | 36 participants | 36 participants | 67 participants |
| Vasomotor symptom (VMS) number of participants with number of hot flashes / day 6 - < 9 | 102 participants | 32 participants | 31 participants | 39 participants |
| Vasomotor symptom (VMS) number of participants with number of hot flashes / day 9 - < 12 | 45 participants | 11 participants | 15 participants | 19 participants |
| Years since final menstrual period (postmenopausal only) 0 - 5 | 142 participants | 35 participants | 39 participants | 68 participants |
| Years since final menstrual period (postmenopausal only) > 10 | 42 participants | 16 participants | 13 participants | 13 participants |
| Years since final menstrual period (postmenopausal only) 6 - 10 | 72 participants | 23 participants | 20 participants | 29 participants |
| Years since final menstrual period (postmenopausal only) Not postmenopausal | 83 participants | 23 participants | 24 participants | 36 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 53 / 97 | 65 / 96 | 88 / 146 |
| serious Total, serious adverse events | 0 / 97 | 0 / 96 | 0 / 146 |
Outcome results
Primary
Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8
Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 8 study assessment to produce a mean daily frequency for week 8.
Time frame: Week 8
Population: Intention-to-treat, i.e., all participants with follow-up data were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-dose 17-ß-estradiol With Progesterone Taper | Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8 | 3.9 number of hot flashes per day |
| Venlafaxine XR | Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8 | 4.4 number of hot flashes per day |
| Placebo | Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8 | 5.5 number of hot flashes per day |
Comparison: VMS frequency values were log transformed for modeling.p-value: <0.001repeated measures linear model
Comparison: VMS frequency values were log transformed for modeling.p-value: 0.005repeated measures linear model
Primary
Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4
Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 4 study assessment to produce a mean daily frequency for week 4.
Time frame: Week 4
Population: Intention-to-treat, i.e., all participants with follow-up data were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-dose 17-ß-estradiol With Progesterone Taper | Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4 | 5.3 number of hot flashes per day |
| Venlafaxine XR | Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4 | 5.1 number of hot flashes per day |
| Placebo | Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4 | 5.8 number of hot flashes per day |
Secondary
Bothersomeness of Hot Flashes -- Week 4
Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 4.
Time frame: Week 4
Population: Intention-to-treat, i.e., all participants with follow-up data were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-dose 17-ß-estradiol With Progesterone Taper | Bothersomeness of Hot Flashes -- Week 4 | 1.6 units on a scale |
| Venlafaxine XR | Bothersomeness of Hot Flashes -- Week 4 | 1.6 units on a scale |
| Placebo | Bothersomeness of Hot Flashes -- Week 4 | 1.7 units on a scale |
Secondary
Bothersomeness of Hot Flashes -- Week 8
Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 8.
Time frame: Week 8
Population: Intention-to-treat, i.e., all participants with follow-up data were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-dose 17-ß-estradiol With Progesterone Taper | Bothersomeness of Hot Flashes -- Week 8 | 1.4 units on a scale |
| Venlafaxine XR | Bothersomeness of Hot Flashes -- Week 8 | 1.4 units on a scale |
| Placebo | Bothersomeness of Hot Flashes -- Week 8 | 1.6 units on a scale |
Comparison: Outcome differences between active treatment and placebop-value: 0.01repeated measures linear model
Comparison: Outcome differences between active treatment and placebop-value: 0.07repeated measures linear model
Secondary
Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4
The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference.
Time frame: Week 4
Population: Intention-to-treat, i.e., all participants with follow-up data were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-dose 17-ß-estradiol With Progesterone Taper | Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4 | 18.3 units on a scale |
| Venlafaxine XR | Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4 | 19.8 units on a scale |
| Placebo | Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4 | 24.2 units on a scale |
Secondary
Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8
The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference.
Time frame: Week 8
Population: Intention-to-treat, i.e., all participants with follow-up data were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-dose 17-ß-estradiol With Progesterone Taper | Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8 | 14.6 units on a scale |
| Venlafaxine XR | Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8 | 18.3 units on a scale |
| Placebo | Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8 | 21.5 units on a scale |
Comparison: Outcome differences between active treatment and placebo.p-value: <0.001repeated measures linear model
Comparison: Outcome differences between active treatment and placebop-value: 0.03repeated measures linear model
Secondary
Severity of Hot Flashes -- Week 4
Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS severity for week 4.
Time frame: Week 4
Population: Intention-to-treat, i.e., all participants with follow-up data were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-dose 17-ß-estradiol With Progesterone Taper | Severity of Hot Flashes -- Week 4 | 0.7 units on a scale |
| Venlafaxine XR | Severity of Hot Flashes -- Week 4 | 0.7 units on a scale |
| Placebo | Severity of Hot Flashes -- Week 4 | 0.8 units on a scale |
Secondary
Severity of Hot Flashes -- Week 8
Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS severity for week 8.
Time frame: Week 8
Population: Intention-to-treat, i.e., all participants with follow-up data were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-dose 17-ß-estradiol With Progesterone Taper | Severity of Hot Flashes -- Week 8 | 0.6 units on a scale |
| Venlafaxine XR | Severity of Hot Flashes -- Week 8 | 0.6 units on a scale |
| Placebo | Severity of Hot Flashes -- Week 8 | 0.7 units on a scale |
Comparison: Outcome differences between active treatment and placebop-value: 0.02repeated measures linear model
Comparison: Outcome differences between active treatment and placebop-value: 0.02repeated measures linear model