Norethindrone acetate and estradiol-induced endometrial hyperplasia

Objective: To identify the lowest effective continuous dose of norethindron e acetate that significantly reduces 12-month incidence of endometrial hype rplasia associated with unopposed 17 beta-estradiol (E2), 1 mg. Methods: In a double-masked, randomized, multicenter study, 1176 healthy po stmenopausal women 45 years of age or older without evidence of endometrial abnormalities were given 12 months of treatment with unopposed E2, 1 mg, o r continuous-combined regimens of E2, 1 mg, and norethindrone acetate, 0.1 mg, 0.25 mg, or 0.5 mg. Endometrial histology was evaluated at the end of t he treatment period. Results: Continuous-combined E2-norethindrone acetate regimens significantl y reduced 12-month incidence of endometrial hyperplasia compared with unopp osed E2 1 mg (P < .001). Endometrial hyperplasia occurred in 14.6% of women treated with unopposed E2 1 mg, whereas in all continuous-combined groups, the rate decreased to less than 1%. Among patients who received E2-norethi ndrone acei ate 0.1 mg, incidence was 0.8%; among those who received 0.25 m g and 0.5 mg, it was 0.4%. Conclusion: Continuous norethindrone acetate at doses as low as 0.1 mg comb ined with E2 1 mg effectively negated risk for endometrial hyperplasia asso ciated with unopposed E2 1 mg, at least for the first year of therapy. (Obs tet Gynecol 2000;96:373-9. (C) 2000 by The American College of Obstetrician s and Gynecologists).