Estrogen alone and health outcomes in black women by African ancestry: a secondary analyses of a randomized controlled trial

Objective: In postmenopausal black women in the Women's Health Initiative randomized trial, estrogen alone reduced breast cancers but its comprehensive influence on health outcomes in black women is unknown. Therefore, we examined this issue in the Women's Health Initiative overall and by African ancestry. Methods: A total of 1,616 black women with prior hysterectomy, including 1,061 with percent African ancestry determination, at 40 US centers were randomly assigned to conjugated equine estrogen (0.625 mg/d) or placebo for 7.2 years' (median) intervention with 13 years' cumulative follow-up. Coronary heart disease (CHD) and breast cancer were primary efficacy and safety outcomes, respectively. A global index also included stroke, colorectal cancer, hip fracture, pulmonary embolism, and death. Results: Black women in the estrogen-alone group compared with black women in the placebo group had fewer breast cancers (17 vs 40, hazard ratio [HR] 0.47, 95% CI 0.26-0.82). In women with more than 80% African ancestry, breast cancer HR was lower (0.32, 95% CI 0.12-0.86, trend P = 0.04 for ancestry effect). Most other outcomes including CHD, stroke, hip fracture, and the global index were null with estrogen use in black women; a global index effect was more favorable in younger black women (HR 0.65, 95% CI 0.43-0.98). Conclusions: In black postmenopausal women with prior hysterectomy, estrogen alone significantly reduced breast cancer incidence with no adverse influence on CHD, venous thromboembolism, or all-cause mortality. Favorable estrogen-alone global index effects in younger black women warrant further study.