Estrogen after ischemic stroke: clinical basis and design of the Women's Estrogen for Stroke Trial

Abstract

Background and purpose: Observational studies have found that women who take estrogen after menopause are less likely to have a stroke than women who do not take estrogen. Although these findings indicate that estrogen may prevent stroke, an alternative explanation for the improved outcome of estrogen users is that they are healthier before starting therapy than nonusers. To test the therapeutic effect of estrogen with research methods that avoid this selection bias, we designed a randomized controlled trial.

Trial design: The Women's Estrogen For Stroke Trial (WEST) is a double-blind, randomized trial with a primary goal of determining whether 1 mg 17beta-estradiol daily, when compared with placebo, reduces the risk of recurrent stroke or death among postmenopausal women who have experienced a transient ischemic attack or nondisabling ischemic stroke. Exclusion criteria include use of estrogen at the time of stroke, breast or uterine cancer, inability to speak English, and estimated survival less than 5 years. Once randomized, women remain under the care of their personal physicians for management of stroke risk factors. For early detection of endometrial hyperplasia and cancer, asymptomatic women receive medroxyprogesterone yearly (5 mg for 12 days) and vaginal ultrasonography or biopsy at the end of the trial. Unscheduled uterine bleeding is evaluated with biopsy. A total of 652 women are sought at 20 hospitals in Connecticut and one in Massachusetts.

Conclusions: The WEST promises to provide critical guidance to women and their physicians regarding the effectiveness of estrogen in secondary stroke prevention.