CHICAGO, Illinois — New results from a randomized, placebo-controlled trial of 3-months of therapy with oral micronized progesterone in women in perimenopause who had hot flashes were mixed but suggest a benefit that will need to be replicated in a bigger trial.
Reporting the findings here March 19 at ENDO 2018: The Endocrine Society Annual Meeting, Jerilynn C Prior, MD, of the Center for Menstrual Cycle and Ovulation Research, University of British Columbia, Vancouver, said the study serves to fill "a gap in the literature."
Although there was no significant difference between women taking the micronized progesterone vs those taking placebo in the primary endpoint — hot flushes and night sweats — there was still a numerical reduction among those taking the progesterone, she noted. And the women taking micronized progesterone perceived that their hot flushes were significantly less intense and their night sweats improved compared with those taking placebo.
"Our trial was probably underpowered and we will need to repeat it in larger numbers of women, but it's likely to be beneficial for our [perimenopausal] patients," she told delegates.
It has already been shown that micronized progesterone is effective for hot flashes in menopause, but there has not previously been a clinical trial demonstrating it works prior to it, which her team defined as women who had had a menstrual period in the prior year.
No Effective Therapy for Hot Flashes in Perimenopause
Explaining the burden of perimenopause, Prior said, "Almost a quarter of all women today are in perimenopause. They are often working as well as maintaining a home and caring for children and elders. About 20% of them will need effective treatment for hot flushes and night sweats to continue to be effective."
"And hot flushes occur in 8 of 10 perimenopausal women," she added. "At present there is no effective therapy for them. Although not scientifically proven to be effective, women are often prescribed the birth control pill for hot flush symptoms, which may not be safe because women's risks for blood clots and strokes increases with age and weight gain," she explained.
Asked by Medscape Medical News why these perimenopausal women couldn't just take estrogen and progesterone [as combined hormone replacement therapy] for their vasomotor symptoms (VMS), she said: "The advantage [of progesterone only] in perimenopause is that women already have erratically higher levels of estrogen, and those levels are high because they are not suppressible." Giving estrogen at this stage could therefore drive women to toxic levels, she noted.
She and her team have previously published data on use of micronized progesterone for hot flushes during menopause in 2012, she said, but noted that uptake of micronized progesterone for treating hot flushes is poor overall, although it varies from country to country. In France, for example, it has been widely used for 30 years.
Try Micronized Progesterone First
In the study, she and her colleagues compared oral micronized progesterone (Prometrium, Besins) 300 mg at bedtime with identical placebo over a 3-month experimental phase in 189 women a mean age of 50 years (range 35 to 58 years) and an average body mass index of 26.8 mg/kg2.
Women were excluded if they had taken any hormone for VMS in the past 6 months, with the exclusion of low-dose transdermal progesterone, or if they were using a levonorgestrel intrauterine device.
The 189 women had reported "bothersome" VMS (2/week night sweat awakenings or 56 VMS within a 4-week period). Night sweats awakened 98% of participants more than twice weekly. Groups had similar baseline characteristics, including VMS score, which was a mean 12.2.
The study aimed to detect a clinically important 3-point difference in daily diary-derived VMS score (night and day, intensity and number) between therapies by the third month. Participants were stratified by early (no skipped period) or late perimenopause (67%). Secondary outcomes were self-reported change in VMS intensity and number, rated from much worse (+5) to much better (–5) at the last visit.
VMS scores were highly variable. By the third month, in an intention-to-treat analysis, the rate ratio of VMS score among those on progesterone vs placebo was 0.79, which was a 21% decrease, although it wasn't significant.
But self-reported perceived decreases in intensity were significantly greater on oral micronized progesterone for both median day and night VMS score vs placebo (–3 vs –1 for both; P = .014 and < .001) and median total night sweats and number (–3 vs –2 for each parameter; P = .023 and .015).
And late perimenopausal women had larger improvements than early ones.
No serious adverse events occurred and 93% of patients completed the randomized controlled trial. Adherence by pill counts was high (oral micronized progesterone 91.4%; placebo 84.4%).
"The perceived change data suggest a benefit," noted Prior.
"This first ever perimenopause VMS hormonal and randomized controlled trial of oral micronized progesterone (300 mg) for hot flush/flash and night sweat therapy demonstrated no serious adverse effects and may be effective for VMS in perimenopausal women," she emphasized.
To Medscape Medical News, she said: "Micronized progesterone is bioidentical and its best side effect is sleep." It is therefore worth a trial of this first in perimenopausal women experiencing symptoms before progressing to other therapies, she stressed.
"Better to treat the hot flushes, and see what's left. Often mood and anxiety get better if you're sleeping through the night," she concluded.
The study was funded by the Canadian Institutes for Health Research. Prior has reported no relevant financial relationships.
ENDO 2018. March 19, 2018; Chicago, Illinois. Abstract OR25-7
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Cite this: Micronized Progesterone for Hot Flashes in Perimenopause - Medscape - Mar 21, 2018.