This study is the first randomized placebo-controlled trial of oral micronized progesterone (OMP) for hot flushes and night sweats, aka vasomotor symptoms (VMS). Postmenopausal women within 1 to 10 years of their last menstrual period and experiencing VMS that met the entrance required minimum for both frequency and intensity. The 133 women were randomized to receive either OMP 300 mg nightly at bedtime or placebo for 12 weeks. The average daily VMS score during the last 28 days of the study was the primary outcome. The average VMS score during the baseline was 17 per day. VMS scores improved in both the treatment and placebo groups, but the women taking the OMP received significantly more benefit than those receiving placebo. The differences between the two groups appeared by week 4. Both the frequency and severity decreased more than placebo. The OMP was also more beneficial in frequent-severe symptoms. The average reduction in VMS scores for women taking progesterone was 10.0 and for placebo was 4.4.
How progesterone acts to decrease VMS is not known although we do know that progesterone functions in the hypothalamus to increase core temperature, lower stress hormones that are increased in insomnia and interacts with neurotransmitters similarly to estradiol. One hypothesis is that progesterone alters the sweating threshold.
The primary reason why perimenopausal and recently postmenopausal women seek hormone therapy is for the relief of hot flushes and night sweats, collectively called vasomotor symptoms (VMS). Approximately 65% of postmenopausal women between the ages of 40 and 65 experience these symptoms. For about 7% of women, they experience moderate to severe VMS more than 50 times per week. In addition, VMS can occur for 10 years or more in some women.
In conventional medicine, both estrogens and progestins (synthetic version of a broader category called progestogens) are effective but many women are hesitant due to the complicated issues related to benefits versus risks. Also in conventional medicine, some of the antidepressants have less effect but still considerable ability to treat VMS. Changes in lifestyle, diet and the use of select vitamin and/or herbal preparations also offer many options, some as low as 20% reduction in VMS but others as much as 100%. Most of the research hovers in the 45-55% range of improvement.
Oral micronized progesterone (OMP) is a molecule that is identical to human progesterone- aka natural progesterone or bio-identical progesterone. It has been used in France for over 30 years and in the U.S. since 1998. OMP has many appealing clinical advantages than the synthetic progestogens (progestin). It does not increase blood lipids, has positive effects on the lining of blood vessels, can provide protection to the endometrium (lining of the uterus) when given with an estrogen and can have an added benefit as a sleep aid. Even more compelling is the fact that the progestins but not progesterone has been shown to increase proliferation in the breast tissue of primates and in two French studies, estrogen plus progesterone did not increase the risk of breast cancer where as estrogen plus progestins did. Lastly, in human breast tissue, progesterone (i.e. the natural progesterone) inhibits the proliferative effect of estradiol.
Previously, oral progestins have been shown to be effective for VMS, when given alone. And, when estrogen and progestins are given together, they are more effective than estrogen alone.
This current trial, the first randomized placebo-controlled trial on this issue, is meaningful for clinicians and perimenopausal and postmenopausal women in need of treatment for their VMS. Yet, one more small step for midlife women and one more option to choose from.
Hitchcock C, Prior J. Oral micronized progesterone for vasomotor symptoms-a placebo-controlled randomized trial in healthy postmenopausal women. Menopause 2012;19(8):886-893.