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Progesterone for Perimenopausal Night Sweats

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01464697
Recruitment Status : Completed
First Posted : November 3, 2011
Results First Posted : December 16, 2019
Last Update Posted : December 16, 2019
Sponsor:
Information provided by (Responsible Party):
Jerilynn Prior, University of British Columbia

Brief 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.

Condition or disease Intervention/treatment Phase
Hot Flushes Night Sweats Drug: Oral micronized progesterone Drug: placebo Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 249 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Oral Micronized Progesterone for Perimenopausal Vasomotor Symptoms
Study Start Date : October 2011
Actual Primary Completion Date : June 1, 2018
Actual Study Completion Date : June 1, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: oral micronized progesterone
Oral micronized progesterone is Prometrium 300 mg at bedtime daily
Drug: Oral micronized progesterone
300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks
Other Names:
  • Prometrium
  • Utrogestan

Placebo Comparator: Placebo Comparator
Placebo
Drug: placebo
placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks




Primary Outcome Measures :
  1. Vasomotor Symptoms (VMS)/ VMS Score - at 12 Weeks [ Time Frame: 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.


  2. Frequency of VMS [ Time Frame: 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.

  3. Severity of VMS [ Time Frame: 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.

  4. VMS Score by Early Perimenopause [ Time Frame: 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).

  5. VMS Score by Late Perimenopause [ Time Frame: 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).

  6. Subgroup Analysis for Those With Frequent and Severe VMS - VMS Score [ Time Frame: 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).



Secondary Outcome Measures :
  1. Sleep Problems [ Time Frame: 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)


  2. Anxiety [ Time Frame: 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)

  3. Women's Perceived Changes in Daytime Hot Flushes for Whole Population [ Time Frame: 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.


  4. Women's Perceived Changes in Night Sweats for Whole Population [ Time Frame: 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.


  5. Women's Perceived Changes in Quality of Sleep for Whole Population [ Time Frame: 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.


  6. Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women [ Time Frame: 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)


  7. Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Early Perimenopause [ Time Frame: 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)


  8. Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Late Perimenopause [ Time Frame: 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)


  9. Perception of Interference of Perimenopausal Body Changes With Usual Activities in Women [ Time Frame: 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)


  10. Perception of Interference of Perimenopausal Mood Changes With Usual Activities in Women [ Time Frame: 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)


  11. Women's Perceived Changes in Daytime Hot Flushes in Early Perimenopause [ Time Frame: 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.


  12. Women's Perceived Changes in Night Sweats in Early Perimenopause [ Time Frame: 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.


  13. Women's Perceived Changes in Daytime Hot Flushes in Late Perimenopause [ Time Frame: 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.


  14. Women's Perceived Changes in Night Sweats in Late Perimenopause [ Time Frame: 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.


  15. Depression Related to Progesterone Therapy in Whole Population [ Time Frame: 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)


  16. Depression Related to Progesterone Therapy in Early Perimenopause [ Time Frame: 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)


  17. Depression Related to Progesterone Therapy in Late Perimenopause [ Time Frame: 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)


  18. Percentage of Women With Perceived Changes in Menstrual Flow [ Time Frame: 12 weeks ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   35 Years to 58 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01464697


Locations
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Canada, British Columbia
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, Canada, V5Z 1M9
Sponsors and Collaborators
University of British Columbia
Investigators
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Principal Investigator: Jerilynn C Prior, MD, FRCPC University of British Columbia
  Study Documents (Full-Text)

Documents provided by Jerilynn Prior, University of British Columbia:
Additional Information:
Publications:
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.
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.

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Responsible Party: Jerilynn Prior, Principal Investigator, University of British Columbia
ClinicalTrials.gov Identifier: NCT01464697    
Other Study ID Numbers: H10-02975
First Posted: November 3, 2011    Key Record Dates
Results First Posted: December 16, 2019
Last Update Posted: December 16, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Jerilynn Prior, University of British Columbia:
hot flushes/hot flashes
night sweats
sleep problems
negative mood
anxiety
perimenopause
progesterone
vasomotor symptoms
depression
women's perceived change
perimenopause interference questionnaire
Additional relevant MeSH terms:
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Hot Flashes
Progesterone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs