Progesterone for Symptomatic Perimenopause Treatment

Published online: Jul 07 2011

J. C. Prior

Professor, Endocrinology, University of British Columbia, and Vancouver Coastal Health Research. Institute, Vancouver, Canada V5Z 1M9. Scientific Director, Centre for Menstrual Cycle and Ovulation Research (

Correspondence at: Professor J. C. Prior, Suite 4111, 2775 Laurel Street, Division of Endocrinology, Department of Medicine, University of British Columbia and Vancouver Coastal Health Research Institute, Vancouver, BC V5Z 1M9. Telephone (604) 875-5927, Fax (604) 875-5915; email; websites: and


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 estra- diol (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 pre- menstrual 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 peri- menopausal VMS – more evidence-based data are needed.