Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding

Objective: To evaluate vaginal breeding profiles with lower doses of conjug ated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) as contin uous combined therapy. Design: The Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE ) study, a randomized, double-blind, placebo-controlled trial. Setting: Study centers across the United States. Patient(s): Two thousand six hundred seventy-three healthy, postmenopausal women. Intervention(s): Women received CEE, 0.625 mg/d: CEE, 0.625 mg/d, plus MPA 2.5 mg/d; CEE, 0.45 mg/d; CEE, 0.45 mg/d, plus MPA, 2.5 mg/d; CEE 0.45 mg/d , plus MPA, 1.5 mg/d, CEE, 0.3 mg/d; CEE, 0.3 mg/d, plus MPA, 1.5 mg/d; or placebo for 1 year. Main Outcome Measure(s): Bleeding data were analyzed in efficacy-evaluable and intention-to-treat populations. Result(s): Cumulative amenorrhea and no bleeding rates were higher with low er doses of CEE/MPA than with CEE 0.625/MPA 2.5. A linear trend between tim e since menopause and cumulative amenorrhea was observed (P<.05) in all CEE /MPA groups except the CEE 0.45/MPA 1.5 group. The proportion of patients w ho experienced no bleeding in cycle 1 was 89%, 82%, and 80% in the CEE 0.3/ MPA 1.5, CEE 0.45/MPA 1.5, and CEE 0.45/MPA 2.5 groups, respectively. These values were significantly greater than the incidence of no bleeding in the CEE 0.625/MPA 2.5 group (P<.05). Conclusion(s): Lower-dose regimens of CEE and MPA produce hi,higher rates o f amenorrhea and no bleeding compared with CEE 0.625/MPA 2.5 and may be app ropriate for newly menopausal patients. (Fertil Steril(R) 2001;75:1080-7. ( C)2001 by American Society for Reproductive Medicine.).