Perimenopause: Oral Micronized Progesterone May Reduce Hot Flashes, Night Sweats and Sleep Problems Interview with:

Jerilynn C. Prior, MD Professor in the Department of Medicine Division of Endocrinology and Metabolism University of British Columbia in Vancouver

Dr. Prior

Jerilynn C. Prior, MD
Professor in the Department of Medicine
Division of Endocrinology and Metabolism
University of British Columbia in Vancouver

Dr. Prior has written the second edition of the award-winning book, Estrogen’s Storm Season—Stories of Perimenopause this year as an ebook on Google Play. What is the background for this study?

Response: There is an urgent need for an effective therapy for perimenopausal hot flushes/flashes and night sweats (vasomotor symptoms, VMS). Although often considered “estrogen deficiency symptoms” VMS are common and very problematic for women in the menopause transition and who have not yet been one year without flow. About 23% of North American women are now in the perimenopausal age range. Surprisingly VMS are more common in perimenopause than in menopause; 9% of perimenopausal women have severe VMS as classified by the FDA, meaning more than 50 VMS per week of moderate to intense severity.

The commonly used therapies for VMS in midlife women have not been proven more effective than placebo! That includes combined hormonal contraceptives (CHC) and menopausal-type hormone therapy (MHT) as well as the SSRI/SNRI anti-depressants and gabapentin. Why not just accept that what “works” in menopause will be effective in perimenopause?

Response: Because perimenopause and menopause, although sharing vasomotor symptoms, are as hormonally different at chalk and cheese! Perimenopause is characterized by higher and highly variable estrogen levels and menopause by low and stable ones. In women who have menstruated within the last year, even if they are still ovulatory, progesterone levels are decreasing (compared to premenopausal normal ranges) and in menopause they are very low.

Another reason it is inappropriate to accept therapies that have not been proven in a particular reproductive life phase is that they are likely to carry different risks. CHC, for example, poses more risks for blood clots and for stroke in perimenopause than in premenopause.  MHT likely gives too low a dose of progesterone (usually 100 mg) for the higher levels of estradiol in perimenopause. Why did we decide to test progesterone for perimenopausal VMS?

Response: For three reasons:

  • 1) We had previously shown it was effective, all by itself, for vasomotor symptoms in healthy menopausal women (Hitchcock Menopause 2012);
  • 2) Progesterone levels are lower in perimenopause thus it seems more logical than estrogen; and
  • 3) perimenopausal women often have sleep difficulties with or without night sweats; progesterone has previously been proven to improve deep sleep in several RCTs including our menopause one. What are the main findings? 

Response: We learned that progesterone is likely effective for perimenopausal vasomotor symptoms and well tolerated. In our intent to treat analysis, although the primary outcome based on the third month daily diary of day and night VMS did not quite reach statistical significance, women on progesterone perceived a greater 3-month decrease in night sweats overall than did those on placebo. In addition, the daytime hot flush intensity was significantly decreased on progesterone compared with placebo in women‘s perception.

On a less clinically interesting but important scientific point, since this was the first RCT of vasomotor symptoms solely in perimenopause, we learned that perimenopausal VMS are highly variable.  RCTs, to be adequately powered, will require over twice as many women (about 250) as are required for successful menopause VMS trials (100-150). What should readers take away from your report? 

Response: Oral micronized progesterone (300 mg at bedtime daily—a dose that keeps the blood level in the luteal phase range for 24 hours)  may now be used to treat vasomotor symptoms in their midlife women patients and will likely be successful, especially if these women have previously skipped a menstruation (are in Late Midlife Transition).  This therapy will also likely be safe based on the lack of any serious adverse events in the 189 women this trial 3-month trial or in our previous 3-month menopause vasomotor symptoms trial in 133 women. In this trial, blinded adjudication of adverse events found none that were likely drug related and no woman had to leave the trial due to medication-related problems. What recommendations do you have for future research as a result of this study?

Response: A further trial needs to be performed that is adequately powered to show a significant difference.

We have collected but not yet analyzed change over the trial in the clinical tool for assessing depression, PHQ-9, as well as a daily report of feelings of anxiety.

A larger and longer trial needs to examine the breast cancer risks, changes in menstrual flow and quality of life in perimenopausal women treated in a double-blind, comparative trial with oral micronized progesterone versus with combined hormonal contraceptives. Is there anything else you would like to add? 

Response: The progesterone sleep benefit is major for women who are also awakening in the middle of the night. Women highly value this effect of oral micronized progesterone (that progestins and transdermal progesterone do not share).

Any disclosures?

This was a peer-reviewed, grant fund trial supported by the Canadian Institutes for Health Research (similar for Canada to the National Institutes of Health for the USA). None of the investigators or authors have any conflicts of interest.


  1. Prior JC, Cameron A, Hitchcock CL, et al. Oral micronized progesterone beneficial for perimenopausal hot flushes/flashes and night sweats.Presented at: ENDO 2018: The Endocrine Society Annual Meeting; Chicago, IL; March 17-20, 2018. Abstract OR25-7.
  2. Oral micronized progesterone may decrease perimenopausal hot flushes and night sweats [press release]. Washington, DC: Endocrine Society. Published March 19, 2018. Accessed March 19, 2018.

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Last Updated on March 25, 2018 by Marie Benz MD FAAD