Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies

The age-related decline in serum dehydroepiandrosterone (DHEA) and its sulfated ester (DHEA-S) has suggested that a relative deficiency of these steroids may be causally related to the development of chronic diseases generally associated with aging, including insulin resistance, obesity, cardiovascular disease, cancer, reductions of the immune defense, depression and a general deterioration in the sensation of well-being. The numerous studies which have focused on the link between DHEA and cardiovascular disease have generally been inconsistent, generating much debate and controversy on this issue. The present article is an analysis of studies on the relationship between endogenous DHEA or DHEA-S, obesity and cardiovascular disease risk, as well as DHEA treatment studies. Elevated plasma levels of free DHEA are associated with reduced obesity in both men and women, and with smaller abdominal body fat accumulations in men. However, contradictory results have been reported regarding the relationships between the sulfate ester DHEA-S and adiposity. Age differences in the populations studied may have been a confounding factor in these associations. On the other hand, DHEA-S level is not a predictor of cardiovascular disease endpoints in women, and appears to be a relatively weak one in men. DHEA intervention studies suggest that the effects of DHEA on serum lipids are, at best, modest or non-significant. The uncertainty as to whether endogenous and exogenous DHEA should be considered cardioprotective is related to discrepancies in the literature on this topic. Several studies may have been plagued by methodological problems such as low power, unreliable analytical methods, confounding factors or other differences in the populations studied. As a consequence, the original reports demonstrating dramatic effects of either endogenous or exogenous DHEA on cardiovascular disease risk have never been replicated. We propose that the effects of DHEA on cardiovascular disease risk (either favorable or unfavorable) should be considered to be much more modest than previously believed.