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

OBJECTIVE

To evaluate vaginal bleeding profiles with lower doses of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) as continuous 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 lower doses of CEE/MPA than with CEE 0.625/MPA 2.5. A linear trend between time 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 who 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 higher rates of amenorrhea and no bleeding compared with CEE 0.625/MPA 2.5 and may be appropriate for newly menopausal patients.