Uterine bleeding in postmenopausal women on continuous therapy with estradiol and norethindrone acetate

Objective: To investigate the incidence of uterine bleeding during 12 month s of treatment with 17 beta-estradiol (E2) 1 mg, unopposed or in combinatio n with three doses of norethindrone acetate. Methods: This study was a prospective, double-masked, randomized, multicent er trial. A total of 1176 healthy postmenopausal women age 45 years and old er without evidence of endometrial abnormalities were randomly assigned to receive either unopposed E2 1 mg, or continuous-combined formulations of E2 1 mg and norethindrone acetate 0.1 mg, 0.25 mg, or 0.5 mg. Any spotting or bleeding episodes during the treatment period were recorded in a daily dia ry and reported by weekly telephone calls. Results: The incidence of bleeding was low in the combination groups, even during the initial 3 months of treatment (24-28%), after which it decreased with increasing doses of norethindrone acetate. Conversely, the incidence of bleeding increased over time with unopposed E2 1 mg. After the initial 3 months, the incidence of bleeding among the combination groups was lowest in the norethindrone acetate 0.5 mg group. Among women initiating therapy c lose to menopause, fewer reported bleeding with norethindrone acetate 0.5 m g than with the other combination groups. There was a significantly (P < .0 5) lower discontinuation rate due to bleeding in the norethindrone acetate 0.5 mg group compared with all other treatment groups. Conclusion: Continuous-combined formulations of E2 1 mg with norethindrone acetate 0.1, 0.25, or 0.5 mg are associated with a low incidence of uterine bleeding. After the initial 3 months of treatment, bleeding profiles impro ved with increasing doses of norethindrone acetate. (C) 1999 by The America n College of Obstetricians and Gynecologists.