Progesterone for Symptomatic Perimenopause Treatment – Progesterone politics, physiology and potential for perimenopause

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 (E(2)) levels are dropping/deficient. Evidence shows that with disturbed brain-ovary feedbacks, E(2) 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 E(2) and lower P(4) levels. Because P(4) and E(2) complement/counterbalance each other’s tissue effects, oral micronized P(4) (OMP(4) 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, OMP(4) decreases cyclic VMS, improves sleep and premenstrual mastalgia. Menorrhagia is treated with ibuprofen 200mg/6h plus OMP(4) cycle d 4-28. For insulin resistance, metformin plus cyclic or daily OMP(4) decreases insulin resistance and weight gain. Non-responsive migraines need daily OMP(4) plus usual therapies. VMS and insomnia in late perimenopause respond to daily OMP(4). In summary, OMP(4) 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 OMP(4) for perimenopausal VMS – more evidence-based data are needed.