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Low risk with estrogen therapy in postmenopausal women with prior hysterectomy after 10.7 years

Clinical Question:
What are the health outcomes associated with previous estrogen treatment among women with prior hysterectomy after 10 years of follow-up?

Bottom Line:
After 10.7 years of follow-up, treatment with conjugated equine estrogen (CEE) for a median of 5.9 years in postmenopausal women with prior hysterectomy was not associated with a significantly increased or decreased risk of coronary heart disease, venous thrombolic events, stroke, hip fracture, colorectal cancer, invasive breast cancer, or total mortality. In a subanalysis based on age, risks of adverse outcomes were the lowest in women aged 50 years to 59 years and highest in women aged 70 years to 79 years. (LOE = 1b)

Reference:
LaCroix AZ, Chlebowski RT, Manson JE, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy. A randomized controlled trial. JAMA 2011;305(13):1305-1314.  [PMID:21467283]

Study Design:
Randomized controlled trial (double-blinded)

Funding:
Industry + govt

Allocation:
Concealed

Setting:
Outpatient (any)

Synopsis:
The original Women's Health Initiative estrogen-alone trial was stopped after of a mean of 7.1 years because of an increased risk of stroke in women taking estrogen. These investigators report data on outcomes of the study participants through a mean of 10.7 years of follow-up. In the original trial 10,739 postmenopausal women, aged 50 years to 79 years, with a prior hysterectomy randomly received (concealed allocation assignment) CEE 0.625 mg daily or matched placebo for a median of 5.9 years. Individuals masked to treatment group assignment assessed outcomes. Complete follow-up occurred for 78% of surviving participants. Using intention-to-treat analysis, there were no significant differences in postintervention risks for coronary heart disease, stroke, or venous thrombolic events between the CEE and placebo groups. Similarly, there were no significant differences in the risk of colorectal cancer, invasive breast cancer, total mortality, or global index of chronic disease. The significantly reduced hip fracture risk found in the original trial was not maintained in the postintervention phase. In a subanalysis based on age, the risk of coronary heart disease, total mortality, and the global index of chronic disease were significantly lower in women aged 50 years to 59 years and significantly higher in women aged 70 years to 79 years. Based on the authors' analysis, 10,000 women aged 50 years to 59 years receiving CEE had 12 fewer acute myocardial infarctions, 13 fewer deaths, and 18 fewer adverse events than women receiving placebo. Likewise, 10,000 women aged 70 years to 79 years receiving CEE had 16 more acute myocardial infarctions, 19 more deaths, and 48 more adverse events than similar women receiving placebo.

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