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

Eric Roehm

doi:10.1155/2015/713295

Abstract

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.

Highlights

The Women’s Health Initiative (WHI) hormone trials are randomized, double blind, predominantly primary prevention trials, with long-term follow-up evaluating hormone therapy in postmenopausal women
The timing hypothesis, which is supported by primate work [27], proposes that hormone replacement therapy may have an adverse effect when begun late in menopause contrasting with beneficial effects on the more normal vessels typically present in younger women closer to time of menopause [26]
Women 50–59 years of age at time of randomization to conjugated equine estrogens (CEE) or placebo in the WHI Estrogen-Alone Trial were similar in median age to women initiating hormone replacement therapy in clinical practice

Summary

Introduction

The Women’s Health Initiative (WHI) hormone trials are randomized, double blind, predominantly primary prevention trials, with long-term follow-up evaluating hormone therapy in postmenopausal women. The WHI Estrogen-Alone Trial randomized 10,739 postmenopausal women with prior hysterectomy to either 0.625 mg of conjugated equine estrogens (CEE) daily or placebo [1]. The WHI estrogen plus progestin trial randomized 16,608 postmenopausal women with a uterus to a combination of daily 0.625 mg of CEE and 2.5 mg of medroxyprogesterone acetate or placebo [2]. The strengths of these trials derive, in part, from their large size and longterm follow-up, with a 6.6-year median duration of follow-up in the WHI Estrogen-Alone Trial [3] after the completion of the intervention phase. The WHI researchers, in a trial design article when discussing the inclusion of older participants in the trial state, “. . .if the study interventions turn out to be efficacious in terms of relative risk reduction throughout the postmenopausal age range. . . [9]” indicating an awareness by the investigators prior to trial results being available that trial outcomes may vary with age

Methods

Results

Conclusion