Howard N. Hodis, MD; Wendy J. Mack, PhD; Roger A. Lobo, MD; Donna Shoupe, MD; Alex Sevanian, PhD; Peter R. Mahrer, MD; Robert H. Selzer, MS; Chao-ran Liu, MD; Ci-hua Liu, MD; Stanley P. Azen, PhD; Estrogen in the Prevention of Atherosclerosis Trial Research Group*
Acknowledgments: The authors thank the EPAT participants and their families for their time, effort, and support, and David H. Upmalis, MD, for his insight and foresight in helping us secure funding for this study.
Grant Support: Mead Johnson Laboratories provided an investigator-initiated grant. Also supported in part by grant R01-AG-18798 from the National Institutes of Health. Mead Johnson Laboratories also supplied the micronized 17β-estradiol and placebo pills. Pharmacia & Upjohn Company provided the medroxyprogesterone acetate, Bristol-Myers Squibb Company provided the pravastatin, Merck & Co., Inc., provided the lovastatin and simvastatin, Parke-Davis provided the atorvastatin, and Novartis Pharmaceuticals Corp. provided the fluvastatin.
Requests for Single Reprints: Howard N. Hodis, MD, Atherosclerosis Research Unit, University of Southern California, 2250 Alcazar Street, CSC 132, Los Angeles, CA 90033; e-mail, email@example.com.
Current Author Addresses: Drs. Hodis, C.-R. Liu, and C.-H. Liu: Atherosclerosis Research Unit, University of Southern California, 2250 Alcazar Street, CSC 132, Los Angeles, CA 90033.
Drs. Mack and Azen: Department of Preventive Medicine, University of Southern California, 1540 Alcazar Street, CHP 218, Los Angeles, CA 90033.
Dr. Lobo: College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY 10032.
Dr. Shoupe: Women's and Children's Hospital, University of Southern California, 1240 North Mission Road, Room 8K5, Los Angeles, CA 90033.
Dr. Sevanian: School of Pharmacy, University of Southern California, 1985 Zonal Avenue, PSC 612, Los Angeles, CA 90033.
Dr. Mahrer: Kaiser Permanente Medical Center, 1526 North Edgemont Street, Los Angeles, CA 90027.
Mr. Selzer: Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109.
Author Contributions: Conception and design: H.N. Hodis, W.J. Mack, A. Sevanian, P.R. Mahrer, S.P. Azen.
Analysis and interpretation of the data: H.N. Hodis, W.J. Mack, R.A. Lobo, A. Sevanian, S.P. Azen.
Drafting of the article: H.N. Hodis, W.J. Mack, R.A. Lobo, A. Sevanian, S.P. Azen.
Critical revision of the article for important intellectual content: H.N. Hodis, W.J. Mack, R.A. Lobo, D. Shoupe, A. Sevanian, R.H. Selzer, C.-R. Liu, C.-H. Liu, S.P. Azen.
Final approval of the article: H.N. Hodis, W.J. Mack, R.A. Lobo, D. Shoupe, A. Sevanian, P.R. Mahrer, R.H. Selzer, C.-R. Liu, C.-H. Liu, S.P. Azen.
Provision of study materials or patients: H.N. Hodis, R.A. Lobo, P.R. Mahrer, R.H. Selzer.
Statistical expertise: W.J. Mack, S.P. Azen.
Obtaining of funding: H.N. Hodis, R.A. Lobo.
Administrative, technical, or logistic support: H.N. Hodis, D. Shoupe, A. Sevanian, P.R. Mahrer, R.H. Selzer, C.-R. Liu, C.-H. Liu.
Collection and assembly of data: H.N. Hodis, W.J. Mack, D. Shoupe, A. Sevanian, R.H. Selzer, C.-R. Liu, C.-H. Liu.
Hodis H., Mack W., Lobo R., Shoupe D., Sevanian A., Mahrer P., Selzer R., Liu C., Liu C., Azen S., ; Estrogen in the Prevention of Atherosclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med. 2001;135:939-953. doi: 10.7326/0003-4819-135-11-200112040-00005
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Published: Ann Intern Med. 2001;135(11):939-953.
Coronary heart disease is the leading cause of death in women, and mortality rates from this disease substantially and steadily increase after menopause (1-3). Population studies indicate that estrogen reduces the incidence of coronary heart disease in women. Bilateral oophorectomy before natural menopause increases the risk for coronary heart disease (4). This pattern of risk for coronary heart disease suggests that endogenous estrogens, including 17β-estradiol, play a cardioprotective role before menopause.
More than 40 observational studies have suggested that hormone replacement therapy (HRT) reduces cardiovascular morbidity and mortality in postmenopausal women (5-6). Most of these studies were conducted in healthy postmenopausal women who used unopposed estrogen replacement therapy (ERT). Although observational studies are important, selection bias is a potential problem, especially when studying HRT, since healthier women tend to use hormones (7). Only randomized, controlled trials can ensure that patients are assigned to treatment in an unbiased manner and can establish the efficacy of HRT for reducing the progression of atherosclerosis and its clinical sequelae.
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Cardiology, Dyslipidemia, Coronary Risk Factors, Prevention/Screening.
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