BLEEDING PATTERN AND ENDOMETRIAL CHANGES DURING CONTINUOUS COMBINED HORMONE REPLACEMENT THERAPY

Objective: To establish the optimum oral daily dose of micronized medr oxyprogesterone acetate, given in combination with a fixed oral dose o f estrone (E1) sulfate as hormone replacement therapy, that provides e ndometrial protection and induces cessation of vaginal bleeding. Metho ds: This multicenter, randomized, double-blind study was conducted for 2 years. Five hundred sixty-eight postmenopausal women were randomize d to take E1 sulfate 1.25 mg daily and one of three doses of medroxypr ogesterone acetate (2.5, 5, or 10 mg) daily. Any vaginal bleeding was recorded by patients in a daily diary, and endometrial biopsies were p erformed at entry into the study and at 3, 12, and 24 months. Results: Forty-two percent of all women reported some bleeding at month 3 of t herapy. However, by month 6, 76.5, 80.1, and 80.9% of women were ameno rrheic in the 2.5-, 5-, and 10-mg medroxyprogesterone acetate groups, respectively. Over time, the percentage of women with no bleeding incr eased in each group, and by 24 months 91.5, 89.9, and 94.3% were ameno rrheic in the 2.5- and 10-mg medroxyprogesterone acetate groups, respe ctively. Approximately 10% of women continue to have some bleeding, re gardless of the dose of medroxyprogesterone acetate. There were no sta tistically significant differences in the number of women with bleedin g at any time point between the three groups. There were no cases of e ndometrial hyperplasia reported in the study population over the 2 yea rs. Conclusion: All three studied doses of medroxyprogesterone acetate , given in combination with 1.25 mg of E1 sulfate, provide adequate en dometrial protection and render approximately 80% of women amenorrheic by 6 months of therapy. (C) 1998 by The American College of Obstetric ians and Gynecologists.