American Journal of Epidemiology Advance Access published online on July 20, 2005
American Journal of Epidemiology, doi:10.1093/aje/kwi223
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1 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA
* To whom correspondence should be addressed. Observational research on postmenopausal hormone therapy suggests a 40-50% reduction in coronary heart disease incidence among women using these preparations. In contrast, the Women's Health Initiative clinical trial of estrogen plus progestin found an elevated incidence over a 5.6-year intervention period through July 7, 2002. Toward explaining this discrepancy, the authors analyzed data from this trial, which included 16,608 postmenopausal women aged 50-79 years, and corresponding data from 53,054 women in the Women's Health Initiative observational study, 33% of whom were estrogen-plus-progestin users at baseline. Estrogen-plus-progestin hazard ratio estimates for coronary heart disease, stroke, and venous thromboembolism in the observational study were 39-48% lower than those in the clinical trial following age adjustment. However, hazard ratios tended to decrease with increasing time from initiation of estrogen-plus-progestin use, and observational study hazard ratio estimates are heavily weighted by longer-term use while clinical trial hazard ratio estimates reflect shorter-term use. Following control for time from estrogen-plus-progestin initiation and confounding, hazard ratio estimates were rather similar for the two cohorts, although there was evidence of some remaining difference for stroke. These analyses have implications for both the design and the analysis of observational studies.
Received September 16, 2004
Accepted February 3, 2005
Original Contributions
Combined Postmenopausal Hormone Therapy and Cardiovascular Disease: Toward Resolving the Discrepancy between Observational Studies and the Women's Health Initiative Clinical Trial
2 Department of Family and Preventive Medicine, University of California, San Diego, CA
3 Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA
4 Medstar Research Institute, Hyattsville, MD
5 Department of Obstetrics and Gynecology, Albert Einstein School of Medicine, Bronx, NY
6 John A. Burns School of Medicine, University of Hawaii, Honolulu, HI
7 Division of Epidemiology, Health Policy Institute, Medical College of Wisconsin, Milwaukee, WI
8 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
9 Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, FL
10 Department of Social and Preventive Medicine and Gynecology-Obstetrics, University at Buffalo, Buffalo, NY
Ross L. Prentice, E-mail: rprentic{at}fhcrc.org
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