Guest post by Jerilynn Prior, Centre for Menstrual Cycle and Ovulation Research
It’s been two weeks since Chris Hitchcock and I returned from San Diego’s recent Endocrine Society meetings. We are feeling incredibly happy with the success of our protracted, intense commitments to a controlled trial of oral micronized progesterone (marketed in the USA and Canada as Prometrium®) for night sweats and hot flushes/flashes. At the Endocrine Society we presented the first-ever trial showing that the molecularly identical progesterone by mouth is effective treatment for vasomotor symptoms (VMS = hot flushes/flashes and night sweats)(1). We were also invited to present our data at an Endocrine Society-sponsored press conference.
Why did a scientific study require so much from us? First, this trial started in 2003 as the initial scientific venture of the newly founded Centre for Menstrual Cycle and Ovulation Research–thus CeMCOR’s reputation became tied to this trial. Second, despite concerted efforts, we were never able to obtain peer reviewed funding for this study—we successfully supported it with individual private donations. Finally, because of the “estrogen myth” and its corollary negatives about progesterone, I wanted to gain additional accurate information about how Prometrium® works in women’s cardiovascular system from this same study. For that reason we decided to enroll only very healthy women who were within 1-10 years since their final flow—they had to be non-smokers, without obesity, diabetes, or high blood pressure, and further to have normal measured waist circumference, blood pressure, cholesterol, and fasting blood sugar levels. Therefore many women were interested but few were eligible.
Late last fall when we broke to code on this study, we were ecstatic to discover that our trial was highly successful. After only three months’ therapy with Prometrium® (300 mg at bedtime daily) the 127 (of 133 randomized) women’s vasomotor symptoms score (VMS Score, combination of number of flushes times their intensity during the day and during sleep) was decreased by about 60% on progesterone compared to less than 30% decrease on placebo.
In early June we learned the answer to another important question: Does progesterone effectively treat intense VMS? The answer is yes! Although less than half all the treatment-seeking women in our study met the FDA’s criteria for more than 50 moderate-intense VMS/week, the 30 women who did who were randomized to Prometrium® showed significantly more improvement in hot flushes than did women on placebo.
What were the reactions to this news? Some local doctors said they already knew that progesterone was good for VMS! Others people were curious, or skeptical but many realized the importance of providing women with an effective alternative to estrogen for VMS. Other reactions were predictable—many questions about whether this couldn’t really be explained, somehow, by estrogen (Prometrium® is converted into estrogen—not!). And there were several questions about side effects and alleged serious health risks from progesterone (wrongly attributed because of confusion of progesterone with synthetic progestins). Happily I was able to respond that participants had no serious negative effects—more placebo-treated than Prometrium®-treated women dropped out before completion. And it is likely that in estrogen-treated women progesterone decreases breast cancer risk rather than increasing it as medroxyprogesterone does (2). Because of Prometrium®’s significant sleep benefit (3), some women who entered the trial sleep-deprived experienced short-lived morning drowsiness. But the estrogen myth-related mood, bloating, weight gain, migraine headaches, and breast tenderness did not occur.
An epic journey for me, Chris, and CeMCOR ends in triumph. Now that the dust has settled, I am so grateful that CeMCOR’s many researchers over the last six years dedicated themselves to a world class trial, that local donors made the trial possible, and that the Prometrium® and placebo were provided by Schering Canada (for the first two years) and subsequently by the world-wide manufacturer, Besins Healthcare of Belgium.
Where from here? First, in the fall we will start a new Canadian Institutes of Health Research-funded trial of Progesterone for Perimenopausal Night Sweats using the same design as in this study. Second, I’m tickled to discover what new we can learn about progesterone from analysis of information we have already collected as part of this trial: how women feel through their Daily Menopause Diary® data, and what happens with hot flushes on stopping progesterone and placebo (in particular, do they soar higher than baseline as occurs when estrogen is stopped?). In addition, we will soon know what changes occur in cholesterol and triglyceride levels, thyroid function, blood clot risks, and quality of life in women treated with progesterone rather than placebo. We already know, from a specialized study of blood flow in the forearm, that progesterone does not have negative effects and tends to increase flow like estrogen does (abstract presented at the 2010 Endocrine Society). Finally, we have solid scientific evidence with which to counter the smirking negatives directed at “bioidentical progesterone.”
- Prior JC, Hitchcock CL. Progesterone For Vasomotor Symptoms: A 12-Week Randomized, Masked Placebo-Controlled Trial In Healthy, Normal-Weight Women 1-10 Years Since Final Menstrual Flow. Endocrine Society Abstracts . 2010. Ref Type: Abstract
- Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat 2008; 107(1):103-111.
- Schussler P, Kluge M, Yassouridis A, Dresler M, Held K, Zihl J et al. Progesterone reduces wakefulness in sleep EEG and has no effect on cognition in healthy postmenopausal women. Psychoneuroendocr 2008; 33(8):1124-1131.