Jerilynn C Prior MD FRCPC (on behalf of all authors Professor of Endocrinology / Department of Medicine University of British Columbia  Centre for Menstrual Cycle and Ovulation Research BC Women’s Health Research Institute Vancouver BC Canada

Study Evaluates Progesterone Therapy for Perimenopausal Night Sweats and Hot Flushes Interview with:

Jerilynn C Prior MD FRCPC (on behalf of all authorsProfessor of Endocrinology / Department of Medicine University of British Columbia  Centre for Menstrual Cycle and Ovulation Research BC Women’s Health Research Institute Vancouver BC Canada

Dr. Prior

Jerilynn C Prior MD FRCPC (on behalf of all authors
Professor of Endocrinology / Department of Medicine
University of British Columbia
Centre for Menstrual Cycle and Ovulation Research
BC Women’s Health Research Institute
Vancouver BC Canada What is the background for this study?

Response: Night sweats and hot flushes/flashes (together called vasomotor symptoms, VMS) disturb women who are still menstruating (in perimenopause) are at least as much or more than  menopausal women (without flow for a year or more)1. However, although studies have investigated various treatments for perimenopausal hot flushes/flashes, none have proven effective in these women who are also likely to be having heavy flow, breast tenderness, and premenstrual symptoms related to high and variable estrogen levels. These include randomized controlled trials (RCT) of the birth control pill2, and gel estrogen in women using a progestin-releasing IUD3.
Neither showed that therapy was more effective than placebo; both studied too few participants to provide a clear answer.

Meanwhile, major medical organization guidelines recommend menopausal hormone therapy (MHT, usually of estrogen with a progestin) for any women younger than 60 years old who are bothered by night sweats and hot flushes 4-6. However, there are no scientific RCT studies showing MHT is effective for perimenopausal night sweats and hot flushes. Giving more estrogen to someone whose own estrogen levels are often high, also did not make clinical sense.

We previously performed an RCT showing that oral micronized progesterone (progesterone) was effective for menopausal hot flushes and also improved sleep7. Given that progesterone levels in perimenopausal women are declining, we considered that perimenopausal progesterone therapy for night sweats needed testing. What are the main findings?

Response:  We studied 189 women for one month on no treatment and then for three months randomized to blinded therapy with either progesterone (300 mg at bedtime daily) or identical placebo. Vasomotor symptoms were highly variable and despite this large number of participants for a VMS trial; usually 100 women is sufficient in menopause. The primary objective, overall VMS Score in the third month, was not significantly different between progesterone and placebo.  However, we had previously determined that women considered that a decrease of 3 in VMS Score provided an important benefit. The results of this RCT could not exclude that benefit since the 95% confidence interval include -4.

In addition, at the end of the trial we asked women to tell us what change they perceived in daytime hot flushes, night sweats and sleep.
Women on progesterone perceived a significant improvement in both night sweats and sleep.  Daytime hot flush intensity also significantly decreased, flow did not change and overall perimenopausal interference with daily life improved on progesterone.

There were no significant adverse events or important safety issues. What should readers take away from your report?

Response: The perimenopausal woman who is struggling with night sweats and sleep disturbances right now will likely benefit from a three-month trial of progesterone therapy. It is also apt to improve at least some of her perimenopausal symptoms and to be safe. What recommendations do you have for future research as a result of this study?

Response: We still need a large (with 250+ women) RCT of progesterone for perimenopausal VMS.

If experts believe that MHT would be effective and safe for perimenopausal vasomotor symptoms, they should do an RCT to prove it. Is there anything else you would like to add? Any disclosures?

Response: It is time we got rid of the notion that low estrogen levels cause hot flushes/flashes. Evidence suggests that it is the downward swinging estrogen levels that trigger stress responses in the brain, and change temperature tolerance

We also know that about a quarter of women treated with estrogen-dominant therapy for VMS will have trouble stopping it because their hot flushes suddenly get worse.
To see if this withdrawal rebound happened when menopausal women stopped progesterone, we did this investigation. Progesterone caused no VMS rebound when it was stopped 8. Women being counseled about vasomotor symptoms treatment need to be told this withdrawal difference between estrogen and progesterone.   

Disclosures: I and none of the coauthors of this study published in June, 2023 by Scientific Reports have any conflicts of interest.

Besins Healthcare International, originator and manufacturer of oral micronized progesterone, provided both progesterone and the placebo without cost for this RCT. Also, as we realized that we needed to recruit more women than planned, and our grant had been spent, we obtained an arms-length donation to the University of British Columbia and the Centre for Menstrual Cycle and Ovulation Research from Besins Healthcare International to fund an additional study year.

Reference List:

  1. Williams RE, Kalilani L, DiBenedetti DB, et al. Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States. Climacteric 2008;11(1):32-43.
  2. Casper RF, Dodin S, Reid RL, et al. The effect of 20 ug ethinyl estradiol/1 mg norethindrone acetate (Minestrin TM), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes, and quality of life in symptomatic perimenopausal women. Menopause 1997;4:139-47.
  3. Santoro N, Teal S, Gavito C, et al. Use of a levonorgestrel-containing intrauterine system with supplemental estrogen improves symptoms in perimenopausal women: a pilot study. Menopause 2015;22(12):1301-07.
  4. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism 2015;100(11):3975-4011.
  5. Panel THTPSoTNAMSA. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause 2022;29(7):767-94. doi: 10.1097/GME.0000000000002028
  6. Yuksel N, Evaniuk D, Huang L, et al. Guideline No. 422a: Menopause: Vasomotor Symptoms, Prescription Therapeutic Agents, Complementary and Alternative Medicine, Nutrition, and Lifestyle. J Obstet Gynaecol Can 2021;43(10):1188-204 e1. doi: 10.1016/j.jogc.2021.08.003 [published Online First: 2021/08/15]
  7. Hitchcock CL, Elliott TG, Norman EG, et al. Hot flushes and night sweats differ in associations with cardiovascular markers in healthy early postmenopausal women. Menopause 2012;19(11):1208-14.
  8. Prior JC, Hitchcock CL. Progesterone for hot flush and night sweat treatment – effectiveness for severe vasomotor symptoms and lack of withdrawal rebound. GynecolEndocrinol 2012;28 Suppl 2:7-11.


Prior, J.C., Cameron, A., Fung, M. et al. Oral micronized progesterone for perimenopausal night sweats and hot flushes a Phase III Canada-wide randomized placebo-controlled 4 month trial. Sci Rep 13, 9082 (2023).

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Last Updated on July 17, 2023 by Marie Benz MD FAAD