Oral micronized progesterone for perimenopausal night sweats and hot flushes a Phase III Canada-wide randomized placebo-controlled 4 month trial

Abstract

This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS) treatment. It was a double-blind, randomized trial of 300 mg oral micronized progesterone@bedtime versus placebo for 3-months (m) after a 1-m untreated baseline during 2012/1-2017/4. We randomized untreated, non-depressed, screen- and baseline-eligible by VMS, perimenopausal women (with flow within 1-year), ages 35-58 (n = 189). Participants aged 50 (± SD = 4.6) were mostly White, educated, minimally overweight with 63% in late perimenopause; 93% participated remotely. The 1° outcome was 3rd-m VMS Score difference. Participants recorded VMS number and intensity (0-4 scale)/24 h on a VMS Calendar. Randomization required VMS (intensity 2-4/4) of sufficient frequency and/or ≥ 2/week night sweat awakenings. Baseline total VMS Score (SD) was 12.2 (11.3) without assignment difference. Third-m VMS Score did not differ by therapy (Rate Difference - 1.51). However, the 95% CI [- 3.97, 0.95] P = 0.222, did not exclude 3, a minimal clinically important difference. Women perceived progesterone caused decreased night sweats (P = 0.023) and improved sleep quality (P = 0.005); it decreased perimenopause-related life interference (P = 0.017) without increased depression. No serious adverse events occurred. Perimenopausal night sweats ± hot flushes are variable; this RCT was underpowered but could not exclude a minimal clinically important VMS benefit. Perceived night sweats and sleep quality significantly improved.

Figure 1

Consort figure indicating the flow of participants through the randomized controlled trial of oral micronized progesterone for perimenopausal hot flushes and night sweats (Vasomotor Symptoms).

Figure 2

Dot-plot by experimental therapy (progesterone (n = 93)—blue triangle ∆, placebo (n = 96)—black circle $\bullet$) for Vasomotor Symptom Score* (VMS Score) and for Day and Night Sweat VMS Scores. *The VMS Score was calculated using the number times the intensity of hot flushes added to night sweats; 95% confidence interval for the mean was based on negative binomial distribution. On the X axis “0” is the 1-month baseline, with months 1 through 3 being consecutive trial periods.

Figure 3

Perimenopausal Women’s Perceived Change in Day and Night Vasomotor Symptoms by Progesterone (blue) or Placebo (black) 3-Month Randomized Therapy. The solid line is the median with the box including 50% (25th to 75th percentiles). Negative ratings, as analyzed by Wilcoxon rank-sum test refer to an improvement in the respective experience.

Figure 4

Perimenopausal women’s perceived changes in menstruation and sleep by progesterone (blue) or Placebo (black) 3-Month Randomized Therapy. The solid line is the median with the box including 50% (25th to 75th percentiles). Negative ratings, as analyzed by Wilcoxon rank-sum test, refer to decreased and positive relate to increased respective experiences.