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  Vol. 166 No. 3, February 13, 2006 TABLE OF CONTENTS
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Conjugated Equine Estrogens and Coronary Heart Disease

The Women's Health Initiative

Judith Hsia, MD; Robert D. Langer, MD, MPH; JoAnn E. Manson, MD, DrPH; Lewis Kuller, MD, DrPH; Karen C. Johnson, MD, MPH; Susan L. Hendrix, DO; Mary Pettinger, MS; Susan R. Heckbert, MD, PhD; Nancy Greep, MD; Sybil Crawford, PhD; Charles B. Eaton, MD; John B. Kostis, MD; Pat Caralis, MD; Ross Prentice, PhD; for the Women's Health Initiative Investigators

Arch Intern Med. 2006;166:357-365.

Background  In recent randomized trials, conjugated equine estrogens (CEE) with continuous medroxyprogesterone acetate provided no protection against coronary heart disease in postmenopausal women and may have increased cardiac risk. These trials did not address the role of unopposed estrogen for coronary protection.

Methods  A total of 10 739 women aged 50 to 79 years at baseline (mean age, 63.6 years) who had previously undergone hysterectomy were randomized to receive CEE, 0.625 mg/d, or placebo at 40 US clinical centers beginning in 1993. The trial was terminated early after 6.8 years of follow-up (planned duration, 8.5 years). This report includes final, centrally adjudicated results for the primary efficacy outcome (myocardial infarction or coronary death), secondary coronary outcomes, and subgroup analyses.

Results  During the active intervention period, 201 coronary events were confirmed among women assigned to receive CEE compared with 217 events among women assigned to receive placebo (hazard ratio, 0.95; nominal 95% confidence interval, 0.79-1.16). Among women aged 50 to 59 years at baseline, the hazard ratio for the primary outcome was 0.63 (nominal 95% confidence interval, 0.36-1.08). In that age group, coronary revascularization was less frequent among women assigned to receive CEE (hazard ratio, 0.55; nominal 95% confidence interval, 0.35-0.86), as were several composite outcomes, which included the primary outcome and coronary revascularization (hazard ratio, 0.66; nominal 95% confidence interval, 0.44-0.97).

Conclusions  Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use. There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline.


Author Affiliations: Department of Medicine, George Washington University, Washington, DC (Dr Hsia); Department of Family and Preventive Medicine, University of California at San Diego (Dr Langer); Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (Dr Manson); Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pa (Dr Kuller); Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis (Dr Johnson); Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women's Hospital, Detroit, Mich (Dr Hendrix), Fred Hutchinson Cancer Research Center (Ms Pettinger and Dr Prentice) and Department of Epidemiology, University of Washington, Seattle (Dr Heckbert); Department of Obstetrics and Gynecology, University of California, Irvine (Dr Greep); Department of Medicine, University of Massachusetts Medical School, Worcester (Dr Crawford); Department of Family Medicine and Center for Primary Care and Prevention, Brown University School of Medicine and Memorial Hospital of Rhode Island, Pawtucket (Dr Eaton); Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (Dr Kostis); and University of Miami School of Medicine and Miami Veterans Administration Medical Center, Miami, Fla (Dr Caralis).
Group Information: A complete list of The Women's Health Initiative investigators appears in JAMA (2004;291:1701-1712).


RELATED LETTERS

Estrogen and Heart Disease: Alternatives to a Paradigm in Crisis
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Estrogen and Heart Disease: Alternatives to a Paradigm in Crisis—Reply
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Arch Intern Med. 2006;166(19):2160.
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