Plasma Dehydroepiandrosterone and Risk of Myocardial Infarction in Women (Lipids, Lipoproteins, And Cardiovascular Risk Factors‪)‬

The medical literature suggests that endogenous hormones play a significant role in the etiology of coronary artery disease (1 ). Dehydroepiandrosterone (DHEA) [5] and its sulfated form, dehydroepiandrosterone sulfate (DHEA-S), are adrenal androgens that are precursors of androgens and estrogens (2). Plasma concentrations are lowest before puberty, rapidly increase at puberty through young adulthood, and progressively decline thereafter in an age-dependent manner in both women and men (3 ). As such, supplemental DHEA has been promoted by some as having antiaging properties (4). In the circulation, the predominant form is the largely inactive DHEA-S (5). The primary functions of DHEA and DHEA-S are mostly unknown (6), but they may affect cardiovascular disease risk either through direct influence on risk factors (7) or indirectly via conversion to other steroids. Data on DHEA and DHEA-S with cardiovascular risk are inconsistent, and we do not know how they affect cardiovascular risk in women. Several studies have found DHEA-S to be inversely associated with insulin sensitivity and cardiovascular outcomes. In an angiographic study, men with lower concentrations of DHEA and/or DHEA-S had more severe coronary disease (8). In a small randomized controlled trial, DHEA supplementation in elderly individuals resulted in increased insulin sensitivity and decreased abdominal fat after 6 months (9). In contrast, the concentrations of these adrenal androgens are increased in polycystic ovarian syndrome (10), a disorder associated with increased insulin resistance (11 ). Another randomized trial of DHEA supplementation among elderly men and women did not find statistically significant effects on body composition, quality of life, insulin sensitivity, or physical performance (12). In the Rancho Bernardo study, low DHEA-S was associated with increased cardiovascular mortality in men (13), but no such association was observed in women (who were all older than 50 years) (14). Few data are available in women, and there is a marked difference in the metabolism of DHEA-S in women relative to men. Approximately 50% of the total androgens in the prostate of adult men are derived from adrenal precursors DHEA and DHEA-S (2), whereas in women intracellular conversion of adrenal androgens to estrogens is approximately 75% before menopause and 90% after menopause (2). It has been hypothesized that DHEA and DHEA-S may exhibit antiestrogen effects in high-estrogen environments (15), but act like estrogens in low-estrogen environments (15). The true nature of the relationship between endogenous DHEA and coronary artery disease risk is not known in women. Furthermore, to our knowledge, no prospective study has evaluated the relationship between the more biologically active DHEA and the incidence of cardiovascular disease.