Annals of Internal Medicine Postmenopausal Hormone Therapy Increases Risk for Venous Thromboembolic Disease The Heart and Estrogen/progestin Replacement Study

Background: Oral contraceptive use increases risk for ve-nous thromboembolism, but data on the effect of post-menopausal hormone therapy are limited. Objective: To determine the effect of therapy with estro-gen plus progestin on risk for venous thromboembolic events in postmenopausal women. Design: Randomized, double-blind, placebo-controlled trial. Setting: 20 clinical centers in the United States. Participants: 2763 postmenopausal women younger than 80 years of age (mean age, 67 years) who had coro-nary heart disease but no previous venous thromboembo-lism and had not had a hysterectomy. Intervention: Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in one tablet (n 5 1380) or placebo that was identical in appearance (n 5 1383). Measurements: Documented deep venous thrombosis or pulmonary embolism. Results: During an average of 4.1 years of follow-up, 34 women in the hormone therapy group and 13 in the placebo group experienced venous thromboembolic events (relative hazard, 2.7 [95 % CI, 1.4 to 5.0] [P 5 0.003]; excess risk, 3.9 per 1000 woman-years [CI, 1.4 to 6.4 per 1000 woman-years]; number needed to treat for harm, 256 [CI, 157 to 692]). In multivariate analysis, the risk for venous thromboembolism was increased among women who had lower-extremity fractures (relative hazard, 18.1 [CI, 5.4 to 60.4]) or cancer (relative hazard, 3.9 [CI, 1.6 to 9.4]) and for 90 days after inpatient surgery (relative haz-ard, 4.9 [CI, 2.4 to 9.8]) or nonsurgical hospitalization (relative hazard, 5.7 [CI, 3.0 to 10.8]). Risk was decreased with aspirin (relative hazard, 0.5 [CI, 0.2 to 0.8]) or stati