Prior, J. C. (2011). Progesterone for Symptomatic Perimenopause Treatment - Progesterone politics, physiology and potential for perimenopause. Facts, Views & Vision in ObGyn, 3(2), 109-120.
Prior JC. Progesterone for Symptomatic Perimenopause Treatment - Progesterone politics, physiology and potential for perimenopause. Facts Views Vis Obgyn. 2011;3(2):109-120.
Prior, J. C. "Progesterone for Symptomatic Perimenopause Treatment - Progesterone politics, physiology and potential for perimenopause." Facts, Views & Vision in ObGyn, vol. 3, no. 2, 2011, pp. 109-120.
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RRM Academy Synopsis
Symptomatic perimenopause links to higher estradiol, low progesterone
A 2011 viewpoint article by a hormone doctor looks at perimenopause. It presents progesterone taken by mouth as a therapy for women who have symptoms. The paper enrolls no patients. The author reports that estradiol averages about a quarter higher in perimenopause and progesterone falls. Women with the most symptoms show the biggest shift.
Key Findings
The author states perimenopause is highly symptomatic for about 20% of women. About 80% have vasomotor symptoms, 25% have menorrhagia (heavy bleeding), and about 10% have mastalgia (breast pain).
The author reports that estradiol averages about a quarter higher and swings erratically. Ovulation and progesterone become insufficient or absent. Women with the most symptoms have higher estradiol and lower progesterone.
In a controlled trial the author cites, an oral contraceptive worked no better than placebo for hot flushes in symptomatic perimenopausal women.
In a large French cohort of menopausal women, estrogen with progesterone showed no increased breast cancer risk (95% CI 0.82, 1.22; HR 1.0).
A randomized trial found oral micronized progesterone effective for vasomotor symptoms in healthy early menopausal women. A similar 175-woman perimenopause trial expects results in 2014 at the earliest.
Interpretation
The paper is a viewpoint article. An expert builds an argument from earlier studies and enrolls no new patients. The author knows of no controlled trial data on oral micronized progesterone on heavy flow, migraine or premenstrual symptoms in perimenopause. More evidence-based data are needed. The treatment reasoning draws on trials in other groups, such as menopausal women, and on clinical experience. The hormone findings come from cross-sectional and cohort studies, which show patterns across groups of women. The paper's treatment focus is symptomatic perimenopause.
RRM Context
Progesterone appears only after ovulation. Low progesterone signals a change in the ovulatory cycle. Restorative reproductive medicine treats the ovulatory cycle as a vital sign. It works with the body's own hormone rhythm. The paper compares a hormone-based view with contraceptive pills and menopause hormone therapy.
Our editorial summary of this paper, not the article's abstract.
Abstract
Perimenopause, women's normal midlife reproductive transition, is highly symptomatic for about 20% of women who are currently inaccurately counseled and inappropriately treated with oral contraceptives, menopausal hormone therapy or hysterectomy. About 80% of perimenopausal women experience vasomotor symptoms (VMS), 25% have menorrhagia, and about 10% experience mastalgia. The majority of women describe varying intensities of sleep, -coping or mood difficulties. Women are more symptomatic because common knowledge inaccurately says that estradiol (E2) levels are dropping/deficient. Evidence shows that with disturbed brain-ovary feedbacks, E2 levels average 26% higher and soar erratically - some women describe feeling pregnant! Also, ovulation and progesterone (P4) levels become insufficient or absent. The most symptomatic women have higher E2 and lower P4 levels. Because P4 and E2 complement/counterbalance each other's tissue effects, oral micronized P4 (OMP4 300 mg at -bedtime) is a physiological therapy for treatment-seeking, symptomatic perimenopausal women. Given cyclically (cycle d 14-27, or 14 on/off) in menstruating midlife women, OMP4 decreases cyclic VMS, improves sleep and premenstrual mastalgia. Menorrhagia is treated with ibuprofen 200mg/6h plus OMP4 cycle d 4-28. For insulin resistance, metformin plus cyclic or daily OMP4 decreases insulin resistance and weight gain. Non-responsive migraines need daily OMP4 plus usual therapies. VMS and insomnia in late perimenopause respond to daily OMP4. In summary, OMP4 is a physiology-based therapy that improves sleep, treats VMS, does not increase breast proliferation or cancer risk, increases bone formation and has beneficial cardiovascular effects. A controlled trial is testing OMP4 for perimenopausal VMS - more evidence-based data are needed.
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