(Circulation. 1995;92:5-8.)
© 1995 American Heart Association, Inc.
Articles |
How Do We Explain the Clinical Benefits of Estrogen?
From Bedside to Bench
From the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Peter Ganz, MD, Brigham and Women's Hospital, Cardiac Catheterization Laboratory, L2-196, 75 Francis St, Boston, MA 02115.
Key Words: estrogen replacement therapy • atherosclerosis • Editorials • endothelium
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Introduction |
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Cardiovascular disease claims the lives of 500 000 women in the United States every year.1 Although women are largely protected from clinical coronary disease before the menopause, they rapidly develop increased risk thereafter.2 Both experimental and clinical data suggest that this loss of protection results from a deficiency of endogenous estrogens. Estrogen replacement therapy markedly attenuates the development of dietary atherosclerosis in ovariectomized monkeys.3 4 In epidemiological studies, postmenopausal women taking estrogen replacement therapy experience up to 50% fewer adverse coronary events, with the greatest benefit occurring in women with coronary artery disease.5 6 These observations indicate that estrogen replacement therapy may have an important role in primary and secondary prevention of cardiovascular disease.
Any therapy intended to reduce the risk of fatal and nonfatal myocardial infarction or of sudden coronary death must alter the biology of atherosclerosis, prevent plaque rupture (the proximate cause of sudden coronary occlusion), or reduce its consequences. Vulnerable plaques typically contain a large pool of extracellular lipid, surrounded by a dense inflammatory infiltrate, and are covered by only a thin fibrous cap.7 8 9 10 11 12 Estrogen, directly or indirectly, might retard the development of such plaques, favorably affect the vulnerability of existing plaques, or reduce the risk of coronary occlusion by preventing formation of an occlusive thrombus, a consequence of plaque rupture.13 14 In addition, estrogen may attenuate vasomotor dysfunction, a possible trigger of plaque rupture.
Estrogen may protect women from cardiovascular disease
in part through modification of the lipid profile. Premenopausal women
have reduced LDL and elevated HDL cholesterol compared
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