Effects of Estrogen-Alone on Stroke in the Women’s Health Initiative

May 2006

Findings Summary

The Women’s Health Initiative (WHI) Estrogen Alone (E-Alone) Trial was designed to assess the health benefits and risks of estrogen use in healthy postmenopausal women. In the WHI E-Alone Trial, 10,739 women with prior hysterectomy, aged 50-79 years, were assigned to take either estrogen alone (conjugated estrogens [Premarin®]) or inactive (placebo) study pills. The National Institutes of Health stopped the E-Alone Trial ahead of schedule in February 2004 primarily because of an increased stroke risk for women taking study pills with estrogen alone.
WHI scientists found that estrogen alone caused a significant increase in the risk of ischemic stroke (when blood flow to part of the brain is blocked), but not in hemorrhagic stroke (when blood leaks into part of the brain). Out of 10,000 women per year, 38 in the estrogen alone group, compared with 25 in the placebo group, on average, had an ischemic stroke each year. They did not find that the risk for stroke was different when they compared the risk by subgroup, such as by race/ethnicity, age, smoking status, hypertension status, or prior cardiovascular disease.
Results from the WHI Estrogen plus Progestin Trial in 2002 showed that estrogen with progestin increased the risk for stroke in postmenopausal women. The similarity in results from the two WHI Hormone Trials (Estrogen plus Progestin and E-Alone) strengthens the finding that ischemic stroke risk is higher for women taking the active study pills and implies that estrogen (as opposed to progestin) is the more likely cause. Many women, particularly those who have had a hysterectomy, use estrogen alone therapy for menopausal symptom relief, often for many years. A decision to prescribe or use estrogen therapy should consider the risk of stroke along with the other known risks and benefits of taking estrogen.