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

Abstract

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.

DHEA Induces 11β-HSD2 by Acting on CCAAT/Enhancer-Binding Proteins

“…Many metabolic effects, including antiobesity, antidiabetic, and antiaging properties, have been attributed to DHEA. 4 In rodents, DHEA attenuated ischemia/reperfusion-induced oxidative stress and renal dysfunction, 5 showed beneficial effects in diabetic nephropathy, 6,7 and inhibited the age-related development of proteinuria. 8 DHEA seems to counteract several adverse effects of excessive glucocorticoid action, including a negative correlation between DHEA concentrations and body mass index, visceral adiposity, and impaired insulin sensitivity in elderly individuals 9 ; however, the molecular mechanisms underlying these antiglucocorticoid effects remain unclear.…”

Evaluation of Androgen Levels in Patients with Acute Coronary Syndrome

“…Elevated DHEA-S levels were associated with retarded progression of atherosclerosis measured by coronary artery angiography, ultrasound carotid wall thickness and pulse wave velocity aorta calcification [15]. Low level of DHEA-S causes the insulin resistance, central obesity, cardiovascular disease, immune system dysfunction and psychological problems, and it also accelerates the atherogenic mechanisms [16 -17].…”

Dehydroepiandrosterone Stimulates Phosphorylation of FoxO1 in Vascular Endothelial Cells via Phosphatidylinositol 3-Kinase- and Protein Kinase A-dependent Signaling Pathways to Regulate ET-1 Synthesis and Secretion

“…Moreover, DHEA has biological actions in cell-based systems and animal models that mimic many of the actions of insulin and other hormones important for metabolic, cardiovascular, and neurological function (19,(45)(46)(47)(48)(49). Taken together, these observations have led to the hypothesis that DHEA supplementation may have beneficial health effects in humans to oppose age-related declines in metabolic, cardiovascular, neurological, and musculoskeletal function (50). DHEA is widely used as a popular nutritional supplement with putative anti-aging properties (51).…”