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

Jerilynn C Prior; Andrea Cameron; Michelle Fung; Christine L Hitchcock; Patricia Janssen; Terry Lee; Joel Singer

doi:10.1038/s41598-023-35826-w

Perimenopause and Menopause Hormone Therapy

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

Prior JC, Cameron A, Fung M, Hitchcock CL, Janssen P, Lee T, Singer J

Published June 5, 2023 Scientific Reports, 13(1), 9082

DOI 10.1038/s41598-023-35826-w PMID 37277418 PMC PMC10241804

RRM Academy Synopsis

Progesterone trial for perimenopausal hot flushes was inconclusive

In a trial of 189 perimenopausal women, progesterone did not significantly lower hot flush and night sweat scores after 3 months. Half got a placebo. Women on progesterone felt they had fewer night sweats and better sleep. No serious adverse events occurred.

Key Findings

Of 189 women randomized (93 to progesterone, 96 to placebo), 176 (93%) completed the trial.
Third-month VMS Score did not differ significantly between groups: rate difference -1.51 (95% CI -3.97, 0.95; P = 0.222). The interval did not exclude the authors' minimal clinically important difference of 3.
Women perceived a greater decrease in overall night sweats on progesterone than on placebo (P = 0.023) and improved sleep quality (P = 0.005).
Perimenopause-related life interference decreased more on progesterone (mean difference -6.65, 95% CI -12.11, -1.18; P = 0.017). Third-month PHQ-9 depression scores did not differ (P = 0.501).
No serious adverse events occurred; one woman on progesterone stopped for new-onset atrial fibrillation. Women on progesterone reported numerically more mild to moderate side effects (22 versus 8 on placebo).

Interpretation

This trial was double-blind and placebo-controlled. The study followed 189 women in perimenopause for three months, after a one-month baseline. Hot flush and night sweat scores did not differ much between the two groups. Women on progesterone reported fewer night sweats. They also reported better sleep and less daily interference from symptoms. No serious side effects occurred. The authors note that fewer women joined than planned. They call the trial underpowered. The findings support a larger trial of progesterone for perimenopause symptoms.

RRM Context

Restorative reproductive medicine treats the cycle as a vital sign. That view extends to the hormone shifts of perimenopause. The authors tested progesterone because its levels fall in perimenopause. They cite this drop from a 1996 hormone study.

Our editorial summary of this paper, not the article's abstract.

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.

Topics

Perimenopause and Menopause › Hormone Therapy › Benefits and Risks · Therapeutics › Hormonal Agents › Progesterone and Progestins · Reproductive Endocrinology › Ovarian Hormones › Progesterone

Jerilynn C Prior, Andrea Cameron, Michelle Fung, Christine L Hitchcock, Patricia Janssen, Terry Lee, Joel Singer

J Prior, A Cameron, M Fung, Chris Hitchcock, C Hitchcock, Pat Janssen, Trish Janssen, P Janssen, T Lee, J Singer

PMID 37277418 37277418 DOI 10.1038/s41598-023-35826-w 10.1038/s41598-023-35826-w Prior et al. 2023, Prior 2023

Correction published 2024

Keywords

Progesterone