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THE SEX DIFFERENCE IN ISCHEMIC HEART DISEASE JEROME L. SULUVAN* How are menstruating women protected from ischemic heart disease (IHD)? This is an important question if they are protected by a factor which is also effective in men and postmenopausal women. In years past it was thought that the higher level of circulating estrogen in young women was protective. However, exogenous estrogen worsens the course of men who have had a myocardial infarction [I]. In that study, two pharmacologic dosage levels of conjugated estrogens were studied, 2.5 milligrams per day and 5.0 milligrams per day. These levels are greater than those secreted by normal ovaries in premenopausal women. Both regimens were discontinued because oflack ofefficacy and adverse effects. More recently, elevated endogenous estrogens in men have been considered as a possible risk factor for myocardial infarction [2, 3]. Estrogens may be hazardous for men but beneficial for women. A simpler interpretation is that estrogens are not protective in either sex. Additional evidence has now accumulated suggesting that estrogenic influence is not an adequate explanation for the low incidence of ischemic heart disease in menstruating women. The nature of the protective factor remains an open question. Failure of exogenous estrogen to lower risk in men is disappointing, but it does not exclude the possibility that men can be protected by other factors present in menstruating women. The sex difference in the incidence of IHD in the United States is shown in figure 1 [4], where IHD death rates ofmen and women in 1976 are displayed as a function of age. The two curves are quite similar in shape. The most noticeable difference is that the onset of IHD deaths is about 10 years later in women. Death from IHD is rare in women below the age of 50, but it is clear that women are equal to men in the rapidity with which their death rate rises after that age. The delayed onset of IHD in women results in a sizable male-to-female ratio in the 30-50-year * Department of Pathology, College of Medicine, University of South Florida, 12901 North Thirtieth Street, Tampa, Florida 33612, and Research Service, James A. Haley Veterans Hospital, Tampa, Florida 33612.© 1983 by The University of Chicago. All rights reserved. 0031-5982/83/2604-0363$01.00 Perspectives in Biology and Medicine, 26, 4 · Summer 1983 | 657 cohorts. For the data in figure 1, the greatest sex ratio occurs in the 35-44-year group, with the male rate exceeding the female by a factor of 4.6. This prominent sex difference in IHD is not a universal phenomenon. There is marked variation in the sex difference from country to country. A large sex difference in IHD is usually found in countries with a high prevalence of IHD. In figure 2, the sex ratio of deaths from IHD in 1971-1973 is plotted against age for Finland, England and Wales, United States, Japan, and the Philippines [5]. In general, people in affluent areas ofthe world have much IHD and a correspondingly large sex ratio in younger age groups. In developing countries where IHD is a relatively rare disease, the sex difference often disappears. Japan, a notable exception among the countries in figure 2, has now achieved a sex ratio versus age curve very much like that of the United States, despite an overall prevalence of IHD intermediate between affluent and developing countries. The prevalence of IHD in even older men from the developing countries is remarkably low in comparison with American women [5]. The sex ratio also varies with time within individual countries. As IHD becomes prevalent in a country, a sex differential tends to appear. As IA I o 8000h 600Oh UOOOh 200Oh 35-M H5-5H 55-W 65-74 75-84 85+ Age Fig. 1.—Death rates per 100,000 population for ischemic heart disease by age in years in men (·) and women (O) in the United States in 1976. (Data from [4].) 658 I Jerome L. Sullivan · Ischemic Heart Disease noted by Anderson [6], in the United States and other developed countries , the sex ratio was slightly greater than one and remained stable for the first 2 decades...


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