BACKGROUND. The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. Our 1985 report in the Journal, based on four years of follow-up, suggested that estrogen therapy reduced the risk of coronary heart disease, but a report published simultaneously from the Framingham Study suggested that the risk was increased. In addition, studies of the effect of estrogens on stroke have yielded conflicting results. METHODS. We followed 48,470 postmenopausal women, 30 to 63 years old, who were participants in the Nurses' Health Study, and who did not have a history of cancer or cardiovascular disease at base line. During up to 10 years of follow-up (337,854 person-years), we documented 224 strokes, 405 cases of major coronary disease (nonfatal myocardial infarctions or deaths from coronary causes), and 1263 deaths from all causes. RESULTS. After adjustment for age and other risk factors, the overall relative risk of major coronary disease in women currently taking estrogen was 0.56 (95 percent confidence interval, 0.40 to 0.80); the risk was significantly reduced among women with either natural or surgical menopause. We observed no effect of the duration of estrogen use independent of age. The findings were similar in analyses limited to women who had recently visited their physicians (relative risk, 0.45; 95 percent confidence interval, 0.31 to 0.66) and in a low-risk group that excluded women reporting current cigarette smoking, diabetes, hypertension, hypercholesterolemia, or a Quetelet index above the 90th percentile (relative risk, 0.53; 95 percent confidence interval, 0.31 to 0.91). The relative risk for current and former users of estrogen as compared with those who had never used it was 0.89 (95 percent confidence interval, 0.78 to 1.00) for total mortality and 0.72 (95 percent confidence interval, 0.55 to 0.95) for mortality from cardiovascular disease. The relative risk of stroke when current users were compared with those who had never used estrogen was 0.97 (95 percent confidence interval, 0.65 to 1.45), with no marked differences according to type of stroke. CONCLUSIONS. Current estrogen use is associated with a reduction in the incidence of coronary heart disease as well as in mortality from cardiovascular disease, but it is not associated with any change in the risk of stroke.
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Sato, A., Miura, H., Liu, Y., Somberg, L. B., Otterson, M. F., Demeure, M. J., Schulte, W. J., Eberhardt, L. M., Loberiza, F. R., Sakuma, I., Gutterman, D. D.
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Humphrey, L. L., Chan, B. K.S., Sox, H. C.
(2002). Postmenopausal Hormone Replacement Therapy and the Primary Prevention of Cardiovascular Disease. ANN INTERN MED
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Bureau, I., Laporte, F., Favier, M., Faure, H., Fields, M., Favier, A. E., Roussel, A.-M.
(2002). No Antioxidant Effect of Combined HRT on LDL Oxidizability and Oxidative Stress Biomarkers in Treated Post-Menopausal Women. J. Am. Coll. Nutr.
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Ranki, H. J., Budas, G. R., Crawford, R. M., Davies, A. M., Jovanovic, A.
(2002). 17{beta}-Estradiol regulates expression of KATP channels in heart-derived H9c2 cells. J Am Coll Cardiol
40: 367-374
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Lopez, D., Sanchez, M. D., Shea-Eaton, W., McLean, M. P.
(2002). Estrogen Activates the High-Density Lipoprotein Receptor Gene via Binding to Estrogen Response Elements and Interaction with Sterol Regulatory Element Binding Protein-1A. Endocrinology
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Younan, C., Mitchell, P., Cumming, R. G., Panchapakesan, J., Rochtchina, E., Hales, A. M.
(2002). Hormone Replacement Therapy, Reproductive Factors, and the Incidence of Cataract and Cataract Surgery: : The Blue Mountains Eye Study. Am J Epidemiol
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van Roosmalen, M. S., Verhoef, L. C.G., Stalmeier, P. F.M., Hoogerbrugge, N., van Daal, W. A.J.
(2002). Decision Analysis of Prophylactic Surgery or Screening for BRCA1 Mutation Carriers: A More Prominent Role For Oophorectomy. JCO
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Lee, T.-M., Su, S.-F., Chou, T.-F., Tsai, C.-H.
(2002). Pharmacologic preconditioning of estrogen by activation of the myocardial adenosine triphosphate-sensitive potassium channel in patients undergoing coronary angioplasty. J Am Coll Cardiol
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Christian, R. C., Harrington, S., Edwards, W. D., Oberg, A. L., Fitzpatrick, L. A.
(2002). Estrogen Status Correlates with the Calcium Content of Coronary Atherosclerotic Plaques in Women. J. Clin. Endocrinol. Metab.
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Ling, S., Dai, A., Williams, M. R. I., Myles, K., Dilley, R. J., Komesaroff, P. A., Sudhir, K.
(2002). Testosterone (T) Enhances Apoptosis-Related Damage in Human Vascular Endothelial Cells. Endocrinology
143: 1119-1125
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Golden, S. H., Maguire, A., Ding, J., Crouse, J. R., Cauley, J. A., Zacur, H., Szklo, M.
(2002). Endogenous Postmenopausal Hormones and Carotid Atherosclerosis: A Case-Control Study of the Atherosclerosis Risk in Communities Cohort. Am J Epidemiol
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Eidelman, R. S., Lamas, G. A., Hennekens, C. H., Ridker, P. M.
(2002). Aspirin, Postmenopausal Hormones, and C-Reactive Protein. Arch Intern Med
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Mikkola, T. S, Clarkson, T. B
(2002). Estrogen replacement therapy, atherosclerosis, and vascular function. Cardiovasc Res
53: 605-619
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Chan, H. Y., Yao, X., Tsang, S. Y., Bourreau, J.-P., Chan, F. L., Huang, Y.
(2002). Isoproterenol amplifies 17{beta}-estradiol-mediated vasorelaxation: role of endothelium/nitric oxide and cyclic AMP. Cardiovasc Res
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Nakano, Y., Oshima, T., Ozono, R., Ueda, A., Oue, Y., Matsuura, H., Sanada, M., Ohama, K., Chayama, K., Kambe, M.
(2002). Estrogen replacement suppresses function of thrombin stimulated platelets by inhibiting Ca2+ influx and raising cyclic adenosine monophosphate. Cardiovasc Res
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Babiker, F. A, De Windt, L. J, van Eickels, M., Grohe, C., Meyer, R., Doevendans, P. A
(2002). Estrogenic hormone action in the heart: regulatory network and function. Cardiovasc Res
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