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Several studies indicate that endogenous hormones play a role in the etiology of coronary artery disease, either as independent risk factors or indirectly, via an effect on lipids, lipoproteins, or other heart disease risk factors.The relation between endogenous hormone levels and premature (<56-year-old patients) myocardial infarction was assessed in a retrospective study involving 49 male survivors of premature myocardial infarction and 49 age-matched, volunteer male controls. Serum samples were obtained for each subject the morning after a a ≥12-hour fast and frozen at −70°C for subsequent hormonal analysis. Among the male patients, the average duration between the most recent myocardial infarction and blood sampling was 3.4 years (range, 0.7 to 19.2 years). Individuals reporting the use of any medications with the potential to alter lipid, lipoprotein, or hormone levels were excluded from these analyses. Dehydroepiandrosterone sulfate levels were significantly lower in the patients than in the control subjects. This association remained statistically significant even after accounting for the effects of total cholesterol, triglycerides, the ratio of total to high-density lipoprotein (HDL) cholesterol, HDL, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, and body mass index. There were no significant differences in the levels of estradiol, testosterone, or free testosterone or the ratio of estradiol to testosterone between patients and control subjects.Our conclusions are limited by the retrospective nature of this study. However, these data indicate that serum dehydroepiandrosterone sulfate levels are inversely related to premature myocardial infarction in males and that this association is independent of the effects of several known risk factors for premature myocardial infarction.