The randomized double-blind, placebo-controlled study by Hitchcock and Prior  demonstrates that oral micronized progesterone is more effective than placebo for the treatment of vasomotor symptoms (VMS) in early postmenopausal women. The study included 133 healthy community women with VMS, aged 44–62 years, 1–10 years since final menstruation. Women recorded daily frequency and severity (1–4) of VMS in the Daily Menopause Diary during run-in (4 weeks) and intervention (12 weeks). The average daily VMS score (day frequency × day severity + night frequency × night severity) during the final 28 therapy days was the primary outcome. A VMS score of 17.0 (SD 10.4) was recorded at run-in (VMS frequency 6.8 (SD 3.2) episodes/day). Women were then randomized to progesterone ([i]n[/i] = 75) or placebo ([i]n[/i] = 58). The VMS scores of women taking progesterone were better than those taking placebo (mean adjusted difference -4.3; 95% CI -6.6 to -1.9), with mean reductions of 10.0 (95% CI -12.0 to -8.1) and 4.4 (95% CI -6.6 to -2.2) in the progesterone and placebo arms, respectively. Discontinuation with adverse events was 9% (progesterone, [i]n[/i] = 8; placebo, [i]n[/i] = 4), with no serious cases. These data clearly demonstrated that VMS scores of women taking progesterone were significantly better than those taking placebo, and similar to those obtained in any HRT trials.
Department of Reproductive Medicine and Child Development, Division of Obstetrics & Gynecology ‘P. Fioretti, Pisa University Hospital, Pisa, Italy
Hitchcock CL, Prior JC. Oral micronized progesterone for vasomotor symptoms a placebo-controlled randomized trial in healthy postmenopausal women. Menopause 2012;19:1-8.
Rupprecht R, Holsboer F. Neuropsychopharmacological properties of neuroactive steroids. Steroids 1999;64:8391.
Majewska MD. Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanisms of action and physiological significance. Prog Neurobiol 1992;38:37995.
Freeman EW, Purdy RH, Coutifaris C, Rickels K, Paul SM. Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers. Neuroendocrinology 1993;58:47884.
Montplaisir J, Lorrain J, Denesle R, Petit D. Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause 2001;8:10-16.
Gambacciani M, Ciaponi M, Cappagli B, et al. Effects of low-dose, continuous combined hormone replacement therapy on sleep in symptomatic postmenopausal women. Maturitas 2005;50:91-7.
Panay N. Body-identical hormone replacement. Climacteric 2012;15(Suppl 1):12.
Bouchard P, Panay N, de Villiers TJ, et al. Randomized placebo- and active-controlled study of desvenlafaxine for menopausal vasomotor symptoms. Climacteric 2012;15:1220.