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(Circulation. 2006;113:2425-2434.)
© 2006 American Heart Association, Inc.

Stroke

Effects of Conjugated Equine Estrogen on Stroke in the Women’s Health Initiative

Susan L. Hendrix, DO; Sylvia Wassertheil-Smoller, PhD; Karen C. Johnson, MD, MPH; Barbara V. Howard, PhD; Charles Kooperberg, PhD; Jacques E. Rossouw, MD; Maurizio Trevisan, MD, PhD; Aaron Aragaki, MS; Alison E. Baird, MD, PhD; Paul F. Bray, MD; Julie E. Buring, ScD; Michael H. Criqui, MD, MPH; David Herrington, MD; John K. Lynch, DO, MPH; Stephen R. Rapp, PhD; James Torner, PhD, for the WHI Investigators^*

From the Department of Obstetrics and Gynecology (S.L.H.), Wayne State University School of Medicine/Hutzel Women’s Hospital, Detroit, Mich; The Albert Einstein College of Medicine (S.W.-S.), Bronx, NY; Department of Preventive Medicine (K.C.J.), University of Tennessee Health Science Center, Memphis, Tenn; MedStar Research Institute (B.V.H.), Washington, DC; Fred Hutchinson Cancer Research Center (C.K., A.A.), Seattle, Wash; National Heart, Lung, and Blood Institute (J.E.R.), Bethesda, Md; State University of New York (M.T.), Buffalo, NY; National Institute of Neurological Disorders and Stroke, Stroke Neuroscience Unit (A.E.B.) and Neuroepidemiology Branch (J.K.L.), Bethesda, Md; Baylor College of Medicine (P.F.B.), Houston, Tex; Harvard Medical School (J.E.B.), Boston, Mass; University of California at San Diego (M.H.C.), La Jolla, Calif; Wake Forest University Health Sciences (D.H., S.R.R.), Winston-Salem, NC; and Department of Epidemiology (J.T.), University of Iowa College of Public Health, Iowa City, Iowa.

Correspondence to Susan L. Hendrix, DO, Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, 3990 John R, 7 Brush North, Detroit, MI 48201. E-mail shendrix{at}med.wayne.edu

Received December 14, 2005; revision received March 17, 2006; accepted March 21, 2006.

Background— The Women’s Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database.

Methods and Results— The WHI Estrogen Alone hormone trial is a multicenter, double-blind, placebo-controlled, randomized clinical trial in 10 739 women aged 50 to 79 years who were given daily conjugated equine estrogen (CEE; 0.625 mg; n=5310) or placebo (n=5429). During an average follow-up of 7.1 years, there were 168 strokes in the CEE group and 127 in the placebo group; 80.3% of strokes were ischemic. For all stroke the intention-to-treat hazard ratio [HR] (95% CI) for CEE versus placebo was 1.37 (1.09 to 1.73). The HR (95% CI) was 1.55 (1.19 to 2.01) for ischemic stroke and 0.64 (0.35, 1.18) for hemorrhagic stroke. The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk, including younger and more recently menopausal women and in women with prior or current use of statins or aspirin.

Conclusions— CEE increases the risk of ischemic stroke in generally healthy postmenopausal women. The excess risk appeared to be present in all subgroups of women examined, including younger and more recently menopausal women. There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke.

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