Transdermal progesterone: effects on menopausal symptoms and on thrombotic, anticoagulant, and inflammatory factors in postmenopausal women.

Conventional hormone replacement therapy increases a woman's risk of thrombotic events as evidenced in large prospective clinical trials, including HERS I and the Women's Health Initiative. A possible mechanism for this is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on factors involved in hemostatic balance and inflammation. The objective of this study was to examine the short-term effects of transdermal progesterone on menopausal symptoms and serum levels of hemostatic, inflammatory, and immune signaling factors. In a prospective, randomized, double-blinded, placebo-controlled, crossover study, 30 healthy postmenopausal women received either 20 mg/day of transdermal progesterone or placebo for 4 weeks, followed by a 4-week washout period, and were then crossed over to receive either placebo or active drug for an additional 4 weeks. Baseline, 4-week follow-up, and end-of-study values were obtained for the Greene Climacteric Scale, and for serum levels of total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin III, plasminogen activator inhibitor-1, C-reactive protein, interleukin-6, matrix metalloproteinase-9, and tumor necrosis factor-a. Transdermal progesterone significantly improved Greene Climacteric Scale scores. In sharp contrast to previous studies of conventional hormone replacement therapy, no detrimental effect was observed on any of the hemostatic or inflammatory components examined. Administration of transdermal progesterone at a daily dose of 20 mg significantly relieves menopausal symptoms in postmenopausal women without adversely altering prothrombotic potential. We suggest, therefore, that this treatment be seriously considered as an effective and safe alternative clinical therapy for women suffering from menopausal symptoms.