Effects of conjugated equine estrogen on stroke in the Women's Health Initiative.
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.


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.
Hendrix
Susan L
SL
Department of Obstetrics and Gynecology, Wayne State University School of Medicine/Hutzel Women's Hospital, Detroit, MI, USA. shendrix@med.wayne.edu
Wassertheil-Smoller
Sylvia
S
Johnson
Karen C
KC
Howard
Barbara V
BV
Kooperberg
Charles
C
Rossouw
Jacques E
JE
Trevisan
Maurizio
M
Aragaki
Aaron
A
Baird
Alison E
AE
Bray
Paul F
PF
Buring
Julie E
JE
Criqui
Michael H
MH
Herrington
David
D
Lynch
John K
JK
Rapp
Stephen R
SR
Torner
James
J
D000368:Aged; D003327:Coronary Disease / Q000517:prevention & control*; D004311:Double-Blind Method; D004967:Estrogens / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010352:Patient Dropouts; D017698:Postmenopause; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*
D004967:Estrogens; D004966:Estrogens, Conjugated (USP)