Clinical trial NCT01464697: Progesterone for Perimenopausal Night Sweats
Official title: Oral Micronized Progesterone for Perimenopausal Vasomotor Symptoms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2011-11-03
Enrollment: 249
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Vasomotor Symptoms (VMS)/ VMS Score - at 12 Weeks
timeFrame: 12 weeks
measure: Frequency of VMS
timeFrame: 12 weeks
measure: Severity of VMS
timeFrame: 12 weeks
measure: VMS Score by Early Perimenopause
timeFrame: 12 weeks
measure: VMS Score by Late Perimenopause
timeFrame: 12 weeks
measure: Subgroup Analysis for Those With Frequent and Severe VMS - VMS Score
timeFrame: 12 weeks
Secondary outcomes:
measure: Sleep Problems
timeFrame: 12 weeks
measure: Anxiety
timeFrame: 12 weeks
measure: Women's Perceived Changes in Daytime Hot Flushes for Whole Population
timeFrame: 12 weeks
measure: Women's Perceived Changes in Night Sweats for Whole Population
timeFrame: 12 weeks
measure: Women's Perceived Changes in Quality of Sleep for Whole Population
timeFrame: 12 weeks
measure: Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women
timeFrame: 12 weeks
measure: Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Early Perimenopause
timeFrame: 12 weeks
measure: Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Late Perimenopause
timeFrame: 12 weeks
measure: Perception of Interference of Perimenopausal Body Changes With Usual Activities in Women
timeFrame: 12 weeks
measure: Perception of Interference of Perimenopausal Mood Changes With Usual Activities in Women
timeFrame: 12 weeks
measure: Women's Perceived Changes in Daytime Hot Flushes in Early Perimenopause
timeFrame: 12 weeks
measure: Women's Perceived Changes in Night Sweats in Early Perimenopause
timeFrame: 12 weeks
measure: Women's Perceived Changes in Daytime Hot Flushes in Late Perimenopause
timeFrame: 12 weeks
measure: Women's Perceived Changes in Night Sweats in Late Perimenopause
timeFrame: 12 weeks
measure: Depression Related to Progesterone Therapy in Whole Population
timeFrame: 12 weeks
measure: Depression Related to Progesterone Therapy in Early Perimenopause
timeFrame: 12 weeks
measure: Depression Related to Progesterone Therapy in Late Perimenopause
timeFrame: 12 weeks
measure: Percentage of Women With Perceived Changes in Menstrual Flow
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Participation from home or in-person at University of British Columbia/Centre for Menstrual Cycle and Ovulation Research (CeMCOR)/Women's Health Research Institute
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Jerilynn C Prior, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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.