Progesterone for Perimenopausal Night Sweats

Hot Flushes Clinical Trial

Official title:

Oral Micronized Progesterone for Perimenopausal Vasomotor Symptoms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01464697
• Other study ID #: H10-02975
• Status: Completed
• Phase: Phase 3
• Start date: October 2011
• Est. completion date: June 1, 2018

Study information

• Verified date: November 2019
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test whether a oral micronized progesterone reduces the Vasomotor Symptom Score comprised of the number and severity of hot flushes and night sweats in perimenopausal women. Oral micronized progesterone is molecularly identical to human progesterone, a steroid hormone. It is sold by prescription for use to prevent endometrial cancer in women taking estrogen in menopause. This research study will test whether progesterone reduces perimenopausal hot flushes and night sweats. It will also test whether progesterone improves sleep disturbances and anxiety.

Description:

This is a randomized, double-blind placebo-controlled trial of oral micronized progesterone (300 mg daily at bedtime) for perimenopausal women living anywhere in Canada. Using the self-reported maximum menstrual cycle length in the previous year, women will be stratified as in Early Perimenopause (<60 days) or Late Perimenopause (>=60 days). The design includes a 28-day baseline run-in followed by 12 weeks of randomized therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: June 1, 2018
• Est. primary completion date: June 1, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years to 58 Years

Eligibility

Inclusion Criteria:

1. Between 35-58 years of age

2. At least 4 vasomotor symptoms (VMS) per day, on average, for at least 2/4 weeks or at least 56 over a four-week period. In addition, women should report having VMS of moderate or severe rather than mild intensity. Women reporting fewer VMS than this, but who report night sweats that awaken them from sleep on two or more nights per week will also be included.

3. Perimenopausal status either based on irregularity of menstrual periods, or by onset of new perimenopausal symptoms in women with regular periods.

4. At least one menstrual period within 12 months of study enrollment

5. Ability and willingness to complete the Daily Perimenopause Hot Flush Calendar recording instrument.

6. Ability to understand, speak, read and write English.

7. Women who are at high risk for breast cancer (ie first degree relative with breast cancer, known/suspected history of breast cancer) will be required to have a normal mammogram and clinical breast examination within 12 months of study enrollment.

Exclusion Criteria:

1. VMS without perimenopausal etiology.

2. Women who have had a hysterectomy and/or ovariectomy.

3. Peanut allergy (because peanut oil is used in the progesterone formulation.)

4. Current or recent (within the last 6-mos.) use of hormonal therapies (estrogen, progesterone, hormonal contraceptives, hormonal fertility treatments), or plans to initiate use during the study period. Two exceptions: women using progestin-releasing intrauterine device (IUD) will not be excluded as it is felt that level of hormone released will not have an effect on VMS and women taking very low-dose transdermal progesterone therapies who have VMS and meet inclusion criteria will be considered on a case-by-case basis. If enrolled, women with these exclusion exceptions will be required to continue and document use of these therapies throughout the entire trial.

5. Planned pregnancy or fertility treatment during the study period.

6. Women who are breastfeeding.

7. Participants with a score greater or equal to 15 on the Personal Health Questionnaire (PHQ-9) will be assessed on a case-by-case basis. Women assessed as needing further investigation and/or treatment for depression will be excluded.

Related Conditions & MeSH terms

• Hot Flashes
• Hot Flushes
• Night Sweats

Intervention

Drug:
• Oral micronized progesterone
300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks
• placebo
placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks

Locations

Country	Name	City	State
Canada	Participation from home or in-person at University of British Columbia/Centre for Menstrual Cycle and Ovulation Research (CeMCOR)/Women's Health Research Institute	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

References & Publications (3)

Hitchcock CL, Prior JC. Oral micronized progesterone for vasomotor symptoms--a placebo-controlled randomized trial in healthy postmenopausal women. Menopause. 2012 Aug;19(8):886-93. doi: 10.1097/gme.0b013e318247f07a. — View Citation

Prior JC, Cameron A, Hitchcock CL, et al. Oral Micronized Progesterone Beneficial for Perimenopausal Hot Flushes/Flashes and Night Sweats. Endocrine Reviews 2018;39(2) Abstract-oral presentation at Endocrine Society Conference, Chicago, 2018.

Prior JC, Hitchcock, CL. Progesterone for Vasomotor Symptoms: A 12-week Randomized, Masked Placebo-controlled Trial in Healthy, Normal-Weight Women 1-10 Years Since Final Menstrual Flow (Abstract). Endocrine Reviews 31(3): S51, 2010.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vasomotor Symptoms (VMS)/ VMS Score - at 12 Weeks	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.	12 weeks
Primary	Frequency of VMS	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.	12 weeks
Primary	Severity of VMS	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.	12 weeks
Primary	VMS Score by Early Perimenopause	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).	12 weeks
Primary	VMS Score by Late Perimenopause	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).	12 weeks
Primary	Subgroup Analysis for Those With Frequent and Severe VMS - VMS Score	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).	12 weeks
Secondary	Sleep Problems	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)	12 weeks
Secondary	Anxiety	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)	12 weeks
Secondary	Women's Perceived Changes in Daytime Hot Flushes for Whole Population	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.	12 weeks
Secondary	Women's Perceived Changes in Night Sweats for Whole Population	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.	12 weeks
Secondary	Women's Perceived Changes in Quality of Sleep for Whole Population	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.	12 weeks
Secondary	Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women	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)	12 weeks
Secondary	Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Early Perimenopause	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)	12 weeks
Secondary	Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Late Perimenopause	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)	12 weeks
Secondary	Perception of Interference of Perimenopausal Body Changes With Usual Activities in Women	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)	12 weeks
Secondary	Perception of Interference of Perimenopausal Mood Changes With Usual Activities in Women	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)	12 weeks
Secondary	Women's Perceived Changes in Daytime Hot Flushes in Early Perimenopause	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.	12 weeks
Secondary	Women's Perceived Changes in Night Sweats in Early Perimenopause	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.	12 weeks
Secondary	Women's Perceived Changes in Daytime Hot Flushes in Late Perimenopause	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.	12 weeks
Secondary	Women's Perceived Changes in Night Sweats in Late Perimenopause	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.	12 weeks
Secondary	Depression Related to Progesterone Therapy in Whole Population	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)	12 weeks
Secondary	Depression Related to Progesterone Therapy in Early Perimenopause	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)	12 weeks
Secondary	Depression Related to Progesterone Therapy in Late Perimenopause	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)	12 weeks
Secondary	Percentage of Women With Perceived Changes in Menstrual Flow	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.	12 weeks

External Links

•   Centre for Menstrual Cycle and Ovulation Research