For decades, estrogen was used as a component of hormone replacement therapy to treat menopausal symptoms, including hot flashes, night sweats, and sleep disturbance; however, after several large, prospective studies (e.g., HERS, WHI) questioned the safety of long-term use of HRT, as well as its efficacy to prevent cardiovascular disease, many women have decided to avoid traditional HRT regimens.

While most studies have focused on the use of estrogen to treat menopause-related symptoms, a few studies have explored the use of progesterone in this setting.  

In the first of these studies (Hitchcock and Prior, 2012), a randomized double-blind placebo-controlled trial, 133 healthy women in early menopause (1 to 10 years since the last menstrual period) received oral progesterone (Prometrium, 300 mg at bedtime) or placebo. Compared to women on placebo, those treated with progesterone experienced a greater reduction in the frequency and severity of vasomotor symptoms.  

The next study was presented at ENDO 2018: The Endocrine Society Annual Meeting and was reviewed in Medscape.  This study focused on perimenopausal women; 189 participants who were in early (no skipped period) or late perimenopause (67%) received either oral progesterone (300 mg at bedtime) or placebo.  Compared to women on placebo, those treated with progesterone experienced a greater reduction in the frequency and severity of vasomotor symptoms; however, this finding was not statistically significant.

Although the lead investigator for this study, Jennifer Prior, recommends that oral micronized progesterone should be used first in perimenopausal women who present with vasomotor symptoms, this recommendation seems a bit premature.  She notes that one of the side effects of progesterone is sedation and that this may be beneficial in perimenopausal women who commonly report disrupted sleep.  I would be concerned, however, about the potential for other side effects.  For example, progesterone may increase risk for depression in some women.  On the other hand, there have been studies which indicate that progesterone, after being metabolized to allopregnanolone, may have anxiolytic effects by modulating GABA-A receptors. Less is known about the long-term effects of progesterone use.  

What we can say for certain, however, is that many perimenopausal women suffer from vasomotor symptoms, sleep disturbance, and other menopause-related symptoms over long periods of time, and that these symptoms have a significant impact on quality of life and well-being.

Ruta Nonacs, MD PhD

Micronized Progesterone for Hot Flashes in Perimenopause (Medscape – free subscription)

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