Progesterone for Perimenopausal Night Sweats

NCT01464697 | Completed Phase 3 Results DMC

• 1 other identifier: H10-02975
• Study Type: interventional
• Target: 249
• Locations: 1 country
• Sites: 1

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.

Conditions

Hot Flushes; Night Sweats

Keywords

hot flushes/hot flashes; night sweats; sleep problems; negative mood; anxiety; perimenopause; progesterone; vasomotor symptoms; depression; women's perceived change; perimenopause interference questionnaire

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (18)

• Sleep Problems

  12 weeks

• Anxiety

  12 weeks

• Women's Perceived Changes in Daytime Hot Flushes for Whole Population

  12 weeks

• Women's Perceived Changes in Night Sweats for Whole Population

  12 weeks

• Women's Perceived Changes in Quality of Sleep for Whole Population

  12 weeks

Study Arms (2)

oral micronized progesterone

EXPERIMENTAL

Oral micronized progesterone is Prometrium 300 mg at bedtime daily

Drug: Oral micronized progesterone

Placebo Comparator

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

Oral micronized progesterone DRUG

300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks

Also known as: Prometrium, Utrogestan

oral micronized progesterone

placebo DRUG

placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks

Placebo Comparator

Eligibility Criteria

• Age: 35 Years - 58 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Between 35-58 years of age
• 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.
• Perimenopausal status either based on irregularity of menstrual periods, or by onset of new perimenopausal symptoms in women with regular periods.
• At least one menstrual period within 12 months of study enrollment
• Ability and willingness to complete the Daily Perimenopause Hot Flush Calendar recording instrument.
• Ability to understand, speak, read and write English.
• 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.

You may not qualify if:

• VMS without perimenopausal etiology.
• Women who have had a hysterectomy and/or ovariectomy.
• Peanut allergy (because peanut oil is used in the progesterone formulation.)
• Planned pregnancy or fertility treatment during the study period.
• Women who are breastfeeding.
• 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.

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

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, V5Z 1M9, Canada

Location

Related Publications (3)

• 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.

  BACKGROUND

• 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.

  PMID: 22453200 BACKGROUND

• 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.

  BACKGROUND

Related Links

• Centre for Menstrual Cycle and Ovulation Research

MeSH Terms

Conditions

Hot Flashes; Parasomnias; Anxiety Disorders; Depression

Interventions

Progesterone; Utrogestan

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Limitations and Caveats

Given no previous RCT of VMS only in perimenopause, despite a blinded study assessment, we were still under powered. Women's Perceived Changes assessments, were not congruent with the VMS Score.

Results Point of Contact

• Title: Dr. Jerilynn C. Prior, Professor
• Organization: University of British Columbia

jerilynn.prior@ubc.ca

6048755927

Study Officials

• Jerilynn C Prior, MD, FRCPC

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 31, 2011
• First Posted: November 3, 2011
• Study Start: October 1, 2011
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: December 16, 2019
• Results First Posted: December 16, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)