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

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 (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.