Menopause
Conditions
Brief summary
The study has been designed to look at the transfer from using LNG IUS for contraception only, in reproductive age to using it for endometrial protection in menopausal age. The main area of interest in the study is the pattern of any vaginal bleeding that occurs.
Detailed description
The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer HealthCare AG, Germany. Bayer HealthCare AG, Germany is the sponsor of the trial.
Interventions
DRUGLNG IUS
LNG IUS (initial in vitro release 20 µg/24h) intrauterine for minimum of 9 months and maximum of 60 months - 2 phases: a) Contraception Phase b) HRT Phase. For outcome measures (vaginal bleeding variables), five 90-day Reference Periods were defined, which were used for comparison during statistical analysis: Reference Period -1 in Contraception Phase; Reference Periods 1-4 in HRT Phase. 90-day reference periods for analyzing vaginal bleeding data are defined by WHO guideline. Reference Period -1 is the last 90-day reference period that the subject had before starting the HRT. Reference Period 1 covers the first 90-days of the HRT phase, Reference Period 2 covers days 91 to 180, Reference Period 3 days 181 to 270, and Reference Period 4 days 271 to 360 of the HRT phase.
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
46 Years to 51 Years
Healthy volunteers
No
Inclusion criteria
* Women with intact uterus, regular menstrual cycles and no previous or current climacteric symptoms.
Exclusion criteria
* Pregnancy or lactation. * Previous pelvic infections. * Abnormal bleeding. * Abnormal uterine cavity. * Uterine polyps. * Genital cancer. * Liver diseases. * Alcoholism or drug abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Bleeding Days | Last 90 days in Contraception Phase and first 360 days in Hormone-Replacement Therapy (HRT) Phase | Measured by using Subject Diaries (Subject Reported Data) |
| Number of Spotting Days | Last 90 days in Contraception Phase and first 360 days in HRT Phase | Measured by using Subject Diaries (Subject Reported Data) |
| Percentage of Participants With Successful Treatment | Last 90 days in Contraception Phase and first 360 days in HRT Phase | Definition of successful treatment: * Completion of HRT phase, and * Both, the number of bleeding days and the number of spotting days during HRT was equal to or less than during contraceptive phase, and * The number of bleeding days and the number of spotting days could be calculated for at least 3 out of the first 4 reference periods in HRT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progestogenic Symptom 2: Depressive Mood (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Progestogenic Symptom 3: Acne or Greasy Skin (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Progestogenic Symptom 4: Nausea (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Progestogenic Symptom 5: Edema (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Progestogenic Symptom 6: Decreased Libido (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Climacteric Symptom 1: Hot Flushes (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Assessment of QOL as Measured by Women's Health Questionnaire | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Women's Health Questionnaire (Total Score). For the Total score, the minimum is 36 and maximum is 144. A higher score means the distress and dysfunction are less pronounced. |
| Climacteric Symptom 3: Vaginal Dryness (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Climacteric Symptom 4: Sleep Problems (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Climacteric Symptom 5: Irritability (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Climacteric Symptom 6: Breast Tension (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Progestogenic Symptom 7: Hair Loss (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Progestogenic Symptom 8: Greasy Hair (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Climacteric Symptom 2: Sweating Episodes (as Measured by a VAS) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
| Continuation Rates | At entry, at 2 years, at 4 years | Percentage of subjects continuing in the study at the given time points. |
| Progestogenic Symptom 1: Headache (as Measured by a Visual Analogue Scale (VAS)) | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. |
Countries
Belgium, Finland, Netherlands, United Kingdom
Participant flow
Recruitment details
Only the subjects who reached menopause within max. of 4 years of the contraception phase were eligible for the Hormone-Replacement Therapy (HRT) phase. 58 subjects discontinued the study during the contraception phase before starting the HRT, and 168 subjects who started treatment did not reach menopause.
Pre-assignment details
489 subjects were screened: 394 subjects started treatment and 95 subjects failed screening. Intent-to-treat (ITT) population included all subjects (N=394) who had the LNG IUS inserted, or for whom the insertion was attempted. 322 subjects without major protocol deviations were included in the Per protocol set (PPS).
Participants by arm
| Arm | Count |
|---|---|
| LNG IUS Levonorgestrel Intrauterine System (LNG IUS) (initial in vitro release 20 µg/24h) intrauterine for minimum of 9 months and maximum of 60 months - 2 phases: a) Contraception Phase b) Hormone-Replacement Therapy (HRT) Phase. For outcome measures (vaginal bleeding variables), five 90-day Reference Periods were defined, which were used for comparison during statistical analysis: Reference Period -1 in Contraception Phase; Reference Periods 1-4 in HRT Phase. 90-day reference periods for analyzing vaginal bleeding data are defined by World Health Organization (WHO) guideline. Reference Period -1 is the last 90-day reference period that the subject had before starting the HRT. Reference Period 1 covers the first 90-days of the HRT phase, Reference Period 2 covers days 91 to 180, Reference Period 3 days 181 to 270, and Reference Period 4 days 271 to 360 of the HRT phase. | 394 |
| Total | 394 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Contraception Phase | Adverse Event | 37 |
| Contraception Phase | Lost to Follow-up | 10 |
| Contraception Phase | Physician Decision | 2 |
| Contraception Phase | Protocol Violation | 2 |
| Contraception Phase | Withdrawal by Subject | 7 |
| HRT Phase | Adverse Event | 18 |
| HRT Phase | Lost to Follow-up | 4 |
| HRT Phase | Protocol Violation | 2 |
| HRT Phase | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | LNG IUS |
|---|---|
| Age Continuous | 47.8 years STANDARD_DEVIATION 1.42 |
| Sex: Female, Male Female | 394 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 357 / 394 |
| serious Total, serious adverse events | 25 / 394 |
Outcome results
Primary
Number of Bleeding Days
Measured by using Subject Diaries (Subject Reported Data)
Time frame: Last 90 days in Contraception Phase and first 360 days in Hormone-Replacement Therapy (HRT) Phase
Population: Intention to treat population (ITT); all subjects with adequate bleeding diary data. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reference Period -1 (Contraception Phase) | Number of Bleeding Days | 0 Bleeding days |
| Reference Period 1 (HRT Phase) | Number of Bleeding Days | 0 Bleeding days |
| Reference Period 2 (HRT Phase) | Number of Bleeding Days | 0 Bleeding days |
| Reference Period 3 (HRT Phase) | Number of Bleeding Days | 0 Bleeding days |
| Reference Period 4 (HRT Phase) | Number of Bleeding Days | 0 Bleeding days |
Comparison: Time effect tested with Friedman's two-way analysis of variance (ANOVA). The null-hypothesis is that the means are equal at the reference period tested.p-value: 0.128Friedman's two-way ANOVA
Primary
Number of Spotting Days
Measured by using Subject Diaries (Subject Reported Data)
Time frame: Last 90 days in Contraception Phase and first 360 days in HRT Phase
Population: ITT; all subjects with adequate bleeding diary data. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reference Period -1 (Contraception Phase) | Number of Spotting Days | 4 Spotting days |
| Reference Period 1 (HRT Phase) | Number of Spotting Days | 4 Spotting days |
| Reference Period 2 (HRT Phase) | Number of Spotting Days | 2 Spotting days |
| Reference Period 3 (HRT Phase) | Number of Spotting Days | 1 Spotting days |
| Reference Period 4 (HRT Phase) | Number of Spotting Days | 0 Spotting days |
Comparison: Time effect tested with Friedman's two-way analysis of variance (ANOVA). The null-hypothesis is that the means are equal at the reference period tested.p-value: 0.296Friedman's two-way ANOVA
Primary
Percentage of Participants With Successful Treatment
Definition of successful treatment: * Completion of HRT phase, and * Both, the number of bleeding days and the number of spotting days during HRT was equal to or less than during contraceptive phase, and * The number of bleeding days and the number of spotting days could be calculated for at least 3 out of the first 4 reference periods in HRT
Time frame: Last 90 days in Contraception Phase and first 360 days in HRT Phase
Population: ITT; all subjects eligible for the HRT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reference Period -1 (Contraception Phase) | Percentage of Participants With Successful Treatment | 31 Percentage of participants with success |
Secondary
Assessment of QOL as Measured by Women's Health Questionnaire
Women's Health Questionnaire (Total Score). For the Total score, the minimum is 36 and maximum is 144. A higher score means the distress and dysfunction are less pronounced.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Assessment of QOL as Measured by Women's Health Questionnaire | 104.1 score on a scale | Standard Deviation 17.75 |
| Reference Period 1 (HRT Phase) | Assessment of QOL as Measured by Women's Health Questionnaire | 114.4 score on a scale | Standard Deviation 16.64 |
| Reference Period 2 (HRT Phase) | Assessment of QOL as Measured by Women's Health Questionnaire | 112.9 score on a scale | Standard Deviation 16.32 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Climacteric Symptom 1: Hot Flushes (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Climacteric Symptom 1: Hot Flushes (as Measured by a VAS) | 39.9 score on a scale | Standard Deviation 30.21 |
| Reference Period 1 (HRT Phase) | Climacteric Symptom 1: Hot Flushes (as Measured by a VAS) | 9.4 score on a scale | Standard Deviation 14.88 |
| Reference Period 2 (HRT Phase) | Climacteric Symptom 1: Hot Flushes (as Measured by a VAS) | 11.3 score on a scale | Standard Deviation 18.65 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Climacteric Symptom 2: Sweating Episodes (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Climacteric Symptom 2: Sweating Episodes (as Measured by a VAS) | 43.0 score on a scale | Standard Deviation 29.4 |
| Reference Period 1 (HRT Phase) | Climacteric Symptom 2: Sweating Episodes (as Measured by a VAS) | 14.0 score on a scale | Standard Deviation 19.95 |
| Reference Period 2 (HRT Phase) | Climacteric Symptom 2: Sweating Episodes (as Measured by a VAS) | 17.0 score on a scale | Standard Deviation 21.97 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Climacteric Symptom 3: Vaginal Dryness (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Climacteric Symptom 3: Vaginal Dryness (as Measured by a VAS) | 22.8 score on a scale | Standard Deviation 27.96 |
| Reference Period 1 (HRT Phase) | Climacteric Symptom 3: Vaginal Dryness (as Measured by a VAS) | 13.1 score on a scale | Standard Deviation 20.93 |
| Reference Period 2 (HRT Phase) | Climacteric Symptom 3: Vaginal Dryness (as Measured by a VAS) | 16.7 score on a scale | Standard Deviation 23 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Climacteric Symptom 4: Sleep Problems (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Climacteric Symptom 4: Sleep Problems (as Measured by a VAS) | 39.4 score on a scale | Standard Deviation 29.71 |
| Reference Period 1 (HRT Phase) | Climacteric Symptom 4: Sleep Problems (as Measured by a VAS) | 17.1 score on a scale | Standard Deviation 21.34 |
| Reference Period 2 (HRT Phase) | Climacteric Symptom 4: Sleep Problems (as Measured by a VAS) | 19.9 score on a scale | Standard Deviation 23.93 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Climacteric Symptom 5: Irritability (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Climacteric Symptom 5: Irritability (as Measured by a VAS) | 33.1 score on a scale | Standard Deviation 27.4 |
| Reference Period 1 (HRT Phase) | Climacteric Symptom 5: Irritability (as Measured by a VAS) | 17.2 score on a scale | Standard Deviation 19.47 |
| Reference Period 2 (HRT Phase) | Climacteric Symptom 5: Irritability (as Measured by a VAS) | 19.4 score on a scale | Standard Deviation 20.26 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Climacteric Symptom 6: Breast Tension (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Climacteric Symptom 6: Breast Tension (as Measured by a VAS) | 15.5 score on a scale | Standard Deviation 22.16 |
| Reference Period 1 (HRT Phase) | Climacteric Symptom 6: Breast Tension (as Measured by a VAS) | 13.5 score on a scale | Standard Deviation 20.39 |
| Reference Period 2 (HRT Phase) | Climacteric Symptom 6: Breast Tension (as Measured by a VAS) | 13.0 score on a scale | Standard Deviation 19.42 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: 0.175Friedman's two-way ANOVA
Secondary
Continuation Rates
Percentage of subjects continuing in the study at the given time points.
Time frame: At entry, at 2 years, at 4 years
Population: ITT. Kaplan-Meier estimator given.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Continuation Rates | At Entry | 100.0 Percentage of participants continuing |
| Reference Period -1 (Contraception Phase) | Continuation Rates | At 2 Years | 72.3 Percentage of participants continuing |
| Reference Period -1 (Contraception Phase) | Continuation Rates | At 4 Years | 23.6 Percentage of participants continuing |
Secondary
Progestogenic Symptom 1: Headache (as Measured by a Visual Analogue Scale (VAS))
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Progestogenic Symptom 1: Headache (as Measured by a Visual Analogue Scale (VAS)) | 23.9 score on a scale | Standard Deviation 23.98 |
| Reference Period 1 (HRT Phase) | Progestogenic Symptom 1: Headache (as Measured by a Visual Analogue Scale (VAS)) | 19.1 score on a scale | Standard Deviation 22.57 |
| Reference Period 2 (HRT Phase) | Progestogenic Symptom 1: Headache (as Measured by a Visual Analogue Scale (VAS)) | 18.2 score on a scale | Standard Deviation 23 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: 0.027Friedman's two-way ANOVA
Secondary
Progestogenic Symptom 2: Depressive Mood (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Progestogenic Symptom 2: Depressive Mood (as Measured by a VAS) | 22.3 score on a scale | Standard Deviation 25.69 |
| Reference Period 1 (HRT Phase) | Progestogenic Symptom 2: Depressive Mood (as Measured by a VAS) | 11.8 score on a scale | Standard Deviation 17.31 |
| Reference Period 2 (HRT Phase) | Progestogenic Symptom 2: Depressive Mood (as Measured by a VAS) | 14.6 score on a scale | Standard Deviation 22.1 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Progestogenic Symptom 3: Acne or Greasy Skin (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Progestogenic Symptom 3: Acne or Greasy Skin (as Measured by a VAS) | 8.9 score on a scale | Standard Deviation 14.02 |
| Reference Period 1 (HRT Phase) | Progestogenic Symptom 3: Acne or Greasy Skin (as Measured by a VAS) | 7.3 score on a scale | Standard Deviation 15.38 |
| Reference Period 2 (HRT Phase) | Progestogenic Symptom 3: Acne or Greasy Skin (as Measured by a VAS) | 7.6 score on a scale | Standard Deviation 15.41 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Progestogenic Symptom 4: Nausea (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Progestogenic Symptom 4: Nausea (as Measured by a VAS) | 7.5 score on a scale | Standard Deviation 13.57 |
| Reference Period 1 (HRT Phase) | Progestogenic Symptom 4: Nausea (as Measured by a VAS) | 5.3 score on a scale | Standard Deviation 11.96 |
| Reference Period 2 (HRT Phase) | Progestogenic Symptom 4: Nausea (as Measured by a VAS) | 6.7 score on a scale | Standard Deviation 15.32 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Progestogenic Symptom 5: Edema (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Progestogenic Symptom 5: Edema (as Measured by a VAS) | 15.7 score on a scale | Standard Deviation 20.3 |
| Reference Period 1 (HRT Phase) | Progestogenic Symptom 5: Edema (as Measured by a VAS) | 12.3 score on a scale | Standard Deviation 18.93 |
| Reference Period 2 (HRT Phase) | Progestogenic Symptom 5: Edema (as Measured by a VAS) | 11.7 score on a scale | Standard Deviation 17.65 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: 0.054Friedman's two-way ANOVA
Secondary
Progestogenic Symptom 6: Decreased Libido (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Progestogenic Symptom 6: Decreased Libido (as Measured by a VAS) | 24.9 score on a scale | Standard Deviation 26.29 |
| Reference Period 1 (HRT Phase) | Progestogenic Symptom 6: Decreased Libido (as Measured by a VAS) | 15.6 score on a scale | Standard Deviation 22.06 |
| Reference Period 2 (HRT Phase) | Progestogenic Symptom 6: Decreased Libido (as Measured by a VAS) | 17.5 score on a scale | Standard Deviation 21.13 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA
Secondary
Progestogenic Symptom 7: Hair Loss (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Progestogenic Symptom 7: Hair Loss (as Measured by a VAS) | 10.0 score on a scale | Standard Deviation 15.14 |
| Reference Period 1 (HRT Phase) | Progestogenic Symptom 7: Hair Loss (as Measured by a VAS) | 9.3 score on a scale | Standard Deviation 16.69 |
| Reference Period 2 (HRT Phase) | Progestogenic Symptom 7: Hair Loss (as Measured by a VAS) | 9.0 score on a scale | Standard Deviation 13.63 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: 0.062Friedman's two-way ANOVA
Secondary
Progestogenic Symptom 8: Greasy Hair (as Measured by a VAS)
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Time frame: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase
Population: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reference Period -1 (Contraception Phase) | Progestogenic Symptom 8: Greasy Hair (as Measured by a VAS) | 14.0 score on a scale | Standard Deviation 20.6 |
| Reference Period 1 (HRT Phase) | Progestogenic Symptom 8: Greasy Hair (as Measured by a VAS) | 11.5 score on a scale | Standard Deviation 18.85 |
| Reference Period 2 (HRT Phase) | Progestogenic Symptom 8: Greasy Hair (as Measured by a VAS) | 11.1 score on a scale | Standard Deviation 18.93 |
Comparison: This is a Friedman's two-way analysis of variance (ANOVA) to test the time effect within the treatment group. The null-hypothesis is that the means are equal at the time points tested.p-value: <0.001Friedman's two-way ANOVA