Interactive effects of behavior and reproductive hormones on sex differences in risk for coronary heart disease

It is well known that women in the United States, as in most industrialized countries in the world, are protected from coronary heart disease (CHD), relative to men. It is thought that this protection is by and large due to the effects of female reproductive hormones (i.e., estrogens) on lipid and lipoprotein metabolism and blood pressure, although women's relatively low rates of cigarette smoking are also thought to play a role. However, epidemiological studies that statistically adjust for sex differences in lipids, blood pressure, and smoking status cannot explain sex differences in CHD morbidity and mortality. Also, inconsistent with a simple main-effect model of reproductive hormones are data showing elevated risk of myocardial infarction and stroke among women who use oral contraceptives. Men who are prescribed estrogens have elevated risk of CHD, and case-control studies show that male CHD patients have elevated estradiol, compared to controls. This article suggests that simple main-effect models of female protection from CHD are inadequate. It argues that reproductive hormones are important determinants of protection from CHD, in interaction with behavioral characteristics. It also demonstrates that reproductive hormones can influence behavioral characteristics and that behavioral characteristics can influence the effects of reproductive hormones on CHD risk factors.