A Reappraisal of Women's Health Initiative Estrogen-Alone Trial: Long-Term Outcomes in Women 50–59 Years of Age

The Women's Health Initiative (WHI) Estrogen-Alone Trial randomized postmenopausal women, 50 to 79 years of age, with prior hysterectomy, to conjugated equine estrogens (CEE) or placebo with a 5.9-year median duration of CEE use. In 2013, the WHI published outcomes for additional extended follow-up. Reported here for the first time is an analysis of the number needed to treat with CEE rather than placebo for younger women (50-59 years) to prevent an adverse long-term outcome. For every 76 women randomized to CEE at 50-59 years, one less myocardial infarction occurred during the 13-year cumulative long-term follow-up. For every 37 women randomized to CEE at 50-59 years, one less woman experienced a global index endpoint (including coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, hip fracture, and death) during the 13-year follow-up. Younger women (50-59 years), compared to older women, had more favorable cumulative long-term outcomes for MI and global index. Though a subgroup analysis is not an adequate basis for making primary prevention guideline recommendations, the WHI Estrogen-Alone Trial outcomes strongly suggest that a similar course of estrogen initiated at 50-59 years in postmenopausal women with prior hysterectomy results in significant long-term health benefit.