Trial Outcomes & Findings for Progesterone for Perimenopausal Night Sweats (NCT NCT01464697)

NCT ID: NCT01464697

Last Updated: 2019-12-16

Results Overview

Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity). Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 249 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2019-12-16

Participant Flow

Enrollment required meeting eligibility criteria by screening questionnaire but also required eligible hot flushes and night sweats on a 28-day Calendar. The difference between the listed enrolled and those who were randomized represents this fact.

Participant milestones

Measure	Oral Micronized Progesterone Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Overall Study STARTED	93	96
Overall Study COMPLETED	90	86
Overall Study NOT COMPLETED	3	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Progesterone for Perimenopausal Night Sweats

Baseline characteristics by cohort

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks	Total n=189 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	93 Participants n=93 Participants	96 Participants n=4 Participants	189 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	49.4 years STANDARD_DEVIATION 5.0 • n=93 Participants	50.4 years STANDARD_DEVIATION 4.2 • n=4 Participants	49.9 years STANDARD_DEVIATION 4.6 • n=27 Participants
Sex: Female, Male Female	93 Participants n=93 Participants	96 Participants n=4 Participants	189 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants	9 Participants n=4 Participants	11 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) White	83 Participants n=93 Participants	82 Participants n=4 Participants	165 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=93 Participants	4 Participants n=4 Participants	8 Participants n=27 Participants
Region of Enrollment Canada	93 participants n=93 Participants	96 participants n=4 Participants	189 participants n=27 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Intent to Treat Population

Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows:

Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity).

Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate.

Outcome measures

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Vasomotor Symptoms (VMS)/ VMS Score - at 12 Weeks	5.5 Units of Vasomotor Symptom Score Standard Deviation 8.2	7.1 Units of Vasomotor Symptom Score Standard Deviation 10.4

PRIMARY outcome

Timeframe: 12 weeks

Frequency (count) of hot flushes/hot flashes and night sweats per day from prospective daily calendar records. Outcome is the average daily VMS Frequency (day + night) during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate.

Outcome measures

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Frequency of VMS	2.4 episodes per day Standard Deviation 2.7	3.0 episodes per day Standard Deviation 3.7

PRIMARY outcome

Timeframe: 12 weeks

Severity (0-4, 0=no intensity, 4=extreme intensity) of hot flushes/hot flashes and night sweats per day from prospective daily calendar records. Daily summary score is the maximum of daytime and nighttime severity. Outcome is the average daily severity during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate.

Outcome measures

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Severity of VMS	1.4 Units on a Scale of 0-4 Standard Deviation 1.0	1.5 Units on a Scale of 0-4 Standard Deviation 1.0

PRIMARY outcome

Timeframe: 12 weeks

subgroup analysis of VMS Score by Early Perimenopause (no skipped period or <60 day cycle length). Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity).

Outcome measures

Measure	Oral Micronized Progesterone n=29 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=34 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
VMS Score by Early Perimenopause	4.4 Units of Vasomotor Symptom Score Standard Deviation 7.4	3.9 Units of Vasomotor Symptom Score Standard Deviation 4.0

PRIMARY outcome

Timeframe: 12 weeks

subgroup analysis of VMS Score by Late Perimenopause (those with skipped or ≥60 day cycle lengths). Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity).

Outcome measures

Measure	Oral Micronized Progesterone n=64 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=62 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
VMS Score by Late Perimenopause	5.9 Units of Vasomotor Symptom Score Standard Deviation 8.5	8.8 Units of Vasomotor Symptom Score Standard Deviation 12.3

PRIMARY outcome

Timeframe: 12 weeks

VMS Score for those with more frequent (≥7 per day and moderate to severe episodes of intensity 2-4) at baseline. Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows:

Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity).

Outcome measures

Measure	Oral Micronized Progesterone n=19 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=16 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Subgroup Analysis for Those With Frequent and Severe VMS - VMS Score	11.8 Units of Vasomotor Symptom Score Standard Deviation 9.0	15.1 Units of Vasomotor Symptom Score Standard Deviation 17.1

SECONDARY outcome

Timeframe: 12 weeks

Daily average rating of sleep problems (0-4) from prospective daily calendar records.

Outcome is the average daily rating during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Scale name: Sleep Problems (4=Worst, 0=None)

Outcome measures

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Sleep Problems	0.8 Units on a ordinal Scale Standard Deviation 0.8	1.0 Units on a ordinal Scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: 12 weeks

Daily average rating of anxiety (0-4) from prospective daily calendar records. Outcome is the average daily rating during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Scale name: Anxiety (4=Worst, 0=None)

Outcome measures

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Anxiety	0.5 Units on a ordinal Scale Standard Deviation 0.6	0.6 Units on a ordinal Scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: 12 weeks

Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Daytime Hot Flushes (both number and severity) as recorded on the Final Questionnaire.

Scale Name: Daytime Hot Flush Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. This is women's perception of the change from run-in to when they recorded it at the end of the trial (at 12 weeks).

No calculation is needed.

Outcome measures

Measure	Oral Micronized Progesterone n=90 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=86 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Women's Perceived Changes in Daytime Hot Flushes for Whole Population	-2.3 Change Scale -5 to +5, no change is 0 Standard Deviation 2.3	-1.8 Change Scale -5 to +5, no change is 0 Standard Deviation 2.3

SECONDARY outcome

Timeframe: 12 weeks

Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Nighttime Night Sweats (both number and severity) as recorded on the Final Questionnaire.

Scale Name: Night Sweats Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. This is women's perception of the change from run-in to when they recorded it at the end of the trial (at 12 weeks).

No calculation is needed.

Outcome measures

Measure	Oral Micronized Progesterone n=90 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=86 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Women's Perceived Changes in Night Sweats for Whole Population	-2.5 Change Scale -5 to +5, no change is 0 Standard Deviation 2.0	-1.9 Change Scale -5 to +5, no change is 0 Standard Deviation 2.0

SECONDARY outcome

Timeframe: 12 weeks

Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in the quality of sleep over the three months of the trial as assessed by the Final Questionnaire based on their random assignment to the progesterone or placebo arms of this RCT (Randomized Controlled Trial) and by Early/Late perimenopause.

Scale Name: Quality of Sleep Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. This is women's perception of the change from run-in to when they recorded it at the end of the trial (at 12 weeks).

No calculation is needed.

Outcome measures

Measure	Oral Micronized Progesterone n=90 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=86 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Women's Perceived Changes in Quality of Sleep for Whole Population	2.0 Change Scale -5 to +5, no change is 0 Interval 0.0 to 4.0	0.0 Change Scale -5 to +5, no change is 0 Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: 12 weeks

Final perceptions of interference of overall perimenopausal changes with usual activities (as recorded by the CeMCOR PIQ - Centre for Menstrual Cycle and Ovulation Research Perimenopause Interference Questionnaire) at 12 weeks in women randomized to the progesterone versus to placebo.

Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)

Outcome measures

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women	22.6 Visual Analogue scale 0-100 mm Standard Deviation 18.3	28.2 Visual Analogue scale 0-100 mm Standard Deviation 21.7

SECONDARY outcome

Timeframe: 12 weeks

Final perceptions of interference of overall perimenopausal changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire [CeMCOR PIQ]) at 12 weeks in women randomized to the progesterone versus to placebo.

Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)

Outcome measures

Measure	Oral Micronized Progesterone n=29 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=34 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Early Perimenopause	25.7 Visual Analogue scale 0-100 mm Standard Deviation 20.2	33.0 Visual Analogue scale 0-100 mm Standard Deviation 22.7

SECONDARY outcome

Timeframe: 12 weeks

Final perceptions of interference of overall perimenopausal changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire [CeMCOR PIQ]) at 12 weeks in women randomized to the progesterone versus to placebo.

Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)

Outcome measures

Measure	Oral Micronized Progesterone n=64 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=62 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Late Perimenopause	21.3 Visual Analogue scale 0-100 mm Standard Deviation 17.5	25.6 Visual Analogue scale 0-100 mm Standard Deviation 20.9

SECONDARY outcome

Timeframe: 12 weeks

Final perceptions of interference of perimenopausal body changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire [CeMCOR PIQ]) in women randomized to the progesterone versus to placebo.

Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)

Outcome measures

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Perception of Interference of Perimenopausal Body Changes With Usual Activities in Women	22.4 Visual Analogue scale 0-100 mm Standard Deviation 20.1	27.8 Visual Analogue scale 0-100 mm Standard Deviation 24.2

SECONDARY outcome

Timeframe: 12 weeks

Final perceptions of interference of perimenopausal mood changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire [CeMCOR PIQ]) in women randomized to the progesterone versus to placebo.

Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)

Outcome measures

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Perception of Interference of Perimenopausal Mood Changes With Usual Activities in Women	22.7 Visual Analogue scale 0-100 mm Standard Deviation 20.1	29.3 Visual Analogue scale 0-100 mm Standard Deviation 23.5

SECONDARY outcome

Timeframe: 12 weeks

Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Daytime Hot Flushes (both number and severity) as recorded on the Final Questionnaire and by subgroup for Early Perimenopause.

Scale Name: Perceived Daytime Hot Flush Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5.

Outcome measures

Measure	Oral Micronized Progesterone n=26 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=30 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Women's Perceived Changes in Daytime Hot Flushes in Early Perimenopause	-1.7 Change Scale -5 to +5, no change is 0 Standard Deviation 2.9	-1.3 Change Scale -5 to +5, no change is 0 Standard Deviation 1.8

SECONDARY outcome

Timeframe: 12 weeks

Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Nighttime Night Sweats (both number and severity) as recorded on the Final Questionnaire and by subgroup for Early Perimenopause.

Scale Name: Perceived Night Sweats Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5.

Outcome measures

Measure	Oral Micronized Progesterone n=26 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=30 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Women's Perceived Changes in Night Sweats in Early Perimenopause	-2.9 Change Scale -5 to +5, no change is 0 Standard Deviation 1.9	-1.9 Change Scale -5 to +5, no change is 0 Standard Deviation 1.6

SECONDARY outcome

Timeframe: 12 weeks

Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Daytime Hot Flushes (both number and severity) as recorded on the Final Questionnaire and by subgroup for Late Perimenopause.

Scale Name: Perceived Daytime Hot Flush Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5.

Outcome measures

Measure	Oral Micronized Progesterone n=64 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=56 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Women's Perceived Changes in Daytime Hot Flushes in Late Perimenopause	-2.5 Change Scale -5 to +5, no change is 0 Standard Deviation 2.1	-2.0 Change Scale -5 to +5, no change is 0 Standard Deviation 2.4

SECONDARY outcome

Timeframe: 12 weeks

Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Nighttime Night Sweats (both number and severity) as recorded on the Final Questionnaire and by subgroup for Late Perimenopause.

Scale Name: Perceived Night Sweats Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5.

Outcome measures

Measure	Oral Micronized Progesterone n=64 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=56 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Women's Perceived Changes in Night Sweats in Late Perimenopause	-2.4 Change Scale -5 to +5, no change is 0 Standard Deviation 2.1	-1.9 Change Scale -5 to +5, no change is 0 Standard Deviation 2.2

SECONDARY outcome

Timeframe: 12 weeks

Final PHQ9 (Personal Health Questionnaire 9) Score for Depression related to progesterone therapy in perimenopause will be assessed based on the Personal Health Questionnaire-9 (PHQ-9) score changes within-woman from baseline to the end-of-trial on progesterone compared with placebo.

Scale Name: PHQ9 Scale (0 = No Depression; 27 = Severe Depression)

Outcome measures

Measure	Oral Micronized Progesterone n=93 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Depression Related to Progesterone Therapy in Whole Population	4.8 PHQ9 Scale: 0-27 Standard Deviation 4.4	5.4 PHQ9 Scale: 0-27 Standard Deviation 4.3

SECONDARY outcome

Timeframe: 12 weeks

Final PHQ9 Score for Depression related to progesterone therapy in Early Perimenopause will be assessed based on the Personal Health Questionnaire-9 (PHQ-9) score changes within-woman from baseline to the end-of-trial on progesterone compared with placebo.

Scale Name: PHQ9 Scale (0 = No Depression; 27 = Severe Depression)

Outcome measures

Measure	Oral Micronized Progesterone n=29 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=34 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Depression Related to Progesterone Therapy in Early Perimenopause	6.0 PHQ9 Scale: 0-27 Standard Deviation 4.6	5.4 PHQ9 Scale: 0-27 Standard Deviation 3.6

SECONDARY outcome

Timeframe: 12 weeks

Final PHQ9 Score for Depression related to progesterone therapy in Late Perimenopause will be assessed based on the Personal Health Questionnaire-9 (PHQ-9) score changes within-woman from baseline to the end-of-trial on progesterone compared with placebo.

Scale Name: PHQ9 Scale (0 = No Depression; 27 = Severe Depression)

Outcome measures

Measure	Oral Micronized Progesterone n=64 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=62 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Depression Related to Progesterone Therapy in Late Perimenopause	4.4 PHQ9 Scale: 0-27 Standard Deviation 4.3	5.4 PHQ9 Scale: 0-27 Standard Deviation 4.6

SECONDARY outcome

Timeframe: 12 weeks

Population: The discrepancy in the Number of Participants analyzed is due to missing data on the Final Questionnaire.

Menstrual flow related to progesterone therapy in perimenopause was assessed based on Women's Perceived Changes Questionnaire of changes in the experience of menstrual flow/vaginal bleeding from the Final Questionnaire.

Outcome measures

Measure	Oral Micronized Progesterone n=90 Participants Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=86 Participants Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Percentage of Women With Perceived Changes in Menstrual Flow	65 Participants	74 Participants

Adverse Events

Oral Micronized Progesterone

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo Comparator

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Oral Micronized Progesterone n=93 participants at risk Oral micronized progesterone is Prometrium 300 mg at bedtime daily Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks	Placebo Comparator n=96 participants at risk Placebo placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal, arthritis, connective tissue issues	6.5% 6/93 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.	1.0% 1/96 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.
Gastrointestinal disorders Nausea, GI tract problems	8.6% 8/93 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.	1.0% 1/96 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.
General disorders Dizziness	1.1% 1/93 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.	1.0% 1/96 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.
Cardiac disorders Edema, atrial fibrillation, increased blood pressure, and headache	5.4% 5/93 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.	3.1% 3/96 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.
Reproductive system and breast disorders Worsening VMS	0.00% 0/93 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.	1.0% 1/96 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.
Psychiatric disorders Post-traumatic stress	0.00% 0/93 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.	1.0% 1/96 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.
Psychiatric disorders Probable depression	1.1% 1/93 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.	0.00% 0/96 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.
Skin and subcutaneous tissue disorders Facial acne	1.1% 1/93 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.	0.00% 0/96 • From randomization until the final questionnaire the day after the last experimental therapy, up to 12 weeks. We followed Best Clinical Practice Guidelines. All reported events were included. They were blindly classified by intensity and by potential relationship with the experimental therapy.

Additional Information

Dr. Jerilynn C. Prior, Professor

University of British Columbia

Phone: 6048755927

Email: jerilynn.prior@ubc.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place