Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy: A Randomized Controlled Trial

Study Questions:

Do health outcomes change after stopping conjugated equine estrogens (CEEs) among postmenopausal women with a prior history of hysterectomy?

Methods:

The data used for this analysis were from the Women’s Health Initiative (WHI) Estrogen-Alone Trial. The intervention arm used 0.625 mg/d of CEE, with a comparison arm randomized to placebo.The WHI Estrogen-Alone Trial had been stopped early after a mean of 7.1 years of follow-up because of an increased risk of stroke. The women enrolled were between the ages of 50 and 79 years. The primary outcomes for the present analysis included coronary heart disease (CHD), and invasive breast cancer after a mean of 10.7 years of follow-up (through August of 2009). In addition, a global index of risks and benefits—including these primary outcomes along with stroke, pulmonary embolism, colorectal cancer, hip fracture, and death—was assessed.

Results:

A total of 10,739 women were included in this analysis. CEE use was a median of 5.9 years. Post-intervention risk for CHD among women randomized to CEE was 0.64% compared to 0.67% for the placebo group (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.75-1.25). No difference between the two groups was observed for breast cancer (HR, 0.75; 95% CI, 0.51-1.09) or total mortality (HR, 1.00; 95% CI, 0.84-1.18). The risk of stroke was no longer elevated during the post-intervention follow-up period (HR, 0.89; 95% CI, 0.64-1.24). The risk of deep vein thrombosis (DVT) was lower (HR, 0.63; 95% CI, 0.41-0.98), and the risk of hip fracture did not differ significantly (HR, 1.27; 95% CI, 0.88-1.82). Health outcomes were more favorable for younger compared with older women for CHD (p = 0.05 for interaction), total myocardial infarction (p = 0.007 for interaction), colorectal cancer (p = 0.04 for interaction), total mortality (p = 0.04 for interaction), and global index of chronic diseases (p = 0.009 for interaction).

Conclusions:

The investigators concluded that among postmenopausal women with a prior hysterectomy, CEE use for a median of 5.9 years was not associated with increased or decreased risk of CHD, DVT, stroke, hip fracture, colorectal cancer, or total mortality. A decreased risk of breast cancer did persist through 10.7 years of follow-up.

Perspective:

Information on long-term outcomes among women treated with CEE provides clinicians and patients with key information on risks and benefits related to this form of hormonal therapy, which can be incorporated into decisions regarding the use of CEE after hysterectomy.

Clinical Topics: Vascular Medicine

Keywords: Myocardial Infarction, Follow-Up Studies, Chronic Disease, Estrogens, Conjugated (USP), Pulmonary Embolism, Women's Health, Hysterectomy, Coronary Disease, Colorectal Neoplasms


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