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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00000611.

Conflict of interest statement

Disclosures: Dr. Chlebowski reported receiving consulting fees or honoraria from Novartis, Amgen, Genentech and Genomic Health; fees for participation in review activities for Pfizer and Novo Nordisk; payment for lectures from Novartis and Genentech; and payment for educational activities from Educational Concepts Group. No other authors have conflicts of interest.

Figures

Figure 1. Clinical Outcomes in the Women’s Health Initiative CEE–alone Trial during the intervention phase According to Race

* P–value corresponds to a test of the interaction between randomization arm and race.

Figure 2. Clinical Outcomes in the Women’s Health Initiative CEE–alone Trial for the Overall Combined Phases (Cumulative Follow–up) According to Race

To demonstrate the validity of the case-only analysis, HR (95%CI) estimated from only Black cases that had genetic data available are also displayed, and represented by the gray diamonds. * P–value corresponds to a test of the interaction between randomization arm and race.

Figure 3. Clinical Outcomes in the Women’s Health Initiative CEE–alone Trial for the Overall Combined Phases (Cumulative Follow–up) According to African Ancestry: Case–only Analysis

^ nA and nP are the number of cases in active arm and placebo arm, respectively. * P–value corresponds to a 1 degree–of–freedom test for trend of the interaction between randomization arm and race.

Figure 4. Risk of Global Index in the Women’s Health Initiative CEE-alone Trial for the Overall Combined Phases (Cumulative Follow-up) According to Race Stratified by Select Subgroups

The p-value for the overall effect of CEE on global index corresponds to a test of the interaction between randomization arm and race. For the subgroup analysis, the p-value corresponds to a three-way interaction between randomization group, race and subgroup.