A Reappraisal of WHI Estrogen-Alone Trial: Long-Term Outcomes in Women 50–59 Years of Age

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 7. Conclusions

Women 50–59 years of age at time of randomization to CEE or placebo in the WHI Estrogen-Alone Trial were similar in median age to women initiating hormone replacement therapy in clinical practice. In the intervention phase, for women 50–59 years of age with CEE, there was an increased risk of DVT, gall bladder disease, and stroke, while the reduction in MI, invasive breast cancer, and global index of events was not statistically significant. With cumulative 13-year long-term follow-up, women 50–59 years of age with CEE showed a reduction in MI, as well as a reduced global index of events. The increased risk of stroke and DVT in the intervention phase for women 50–79 years of age, which did not show significant trends with age, declined with cessation of CEE. Long-term follow-up including at least 5 years of follow-up after completion of hormone therapy is necessary to optimally evaluate effects of hormone replacement therapy on cardiovascular, cancer, and mortality outcomes. Though a subgroup analysis does not provide an adequate basis for making guideline recommendations for primary prevention, the preponderance of evidence in the WHI Estrogen-Alone Trial strongly suggests an overall benefit with CEE with cumulative long-term follow-up in women 50–59 years of age. These potential benefits only apply to women with prior hysterectomy and for duration of CEE use similar to what was used in the trial. The WHI Estrogen-Alone Trial data does not provide information on longer durations of use and strongly suggests that initiation of hormone therapy at significantly later ages is harmful.