Dehydroepiandrosterone (DHEA)-A Precursor Steroid or an Active Hormone in Human Physiology

Introduction. The circulation of large amounts of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) suggests a physiological role in human physiology. In the central nervous system, DHEA is considered a neurosteroid with a wide range of functions. Aim. The goal of this review is to discuss metabolism, biochemical, and physiological mechanism of DHEA action and the potential role of DHEA in aging and in ameliorating a host of pathological conditions, associated with aging. Methods. We examined preclinical and clinical data reported in various studies from the available literature concerning the effects of DHEA in normal and pathological conditions. Main Outcome Measures. Data reported in the literature were analyzed, reviewed, and discussed. Results. DHEA mediates its action via multiple signaling pathways involving specific membrane receptors and via transformation into androgen and estrogen derivatives (e.g., androgens, estrogens, 7 alpha and 7 beta DHEA, and 7 alpha and 7 beta epiandrosterone derivatives) acting through their specific receptors. These pathways include: nitric oxide synthase activation, modulation of gamma-amino butyric acid receptors, N-methyl D-aspartate, receptors sigma receptors (Sigma-1), differential expression of inflammatory factors, adhesion molecules and reactive oxygen species, among others. Clinical and epidemiological studies suggested that low DHEA levels might be associated with ischemic heart disease, endothelial dysfunction, atherosclerosis, bone loss, inflammatory diseases, and sexual dysfunction. Most importantly, no significant adverse or negative side effects of DHEA were reported in clinical studies of men and women. Conclusions. DHEA modulates endothelial function, reduces inflammation, improves insulin sensitivity, blood flow, cellular immunity, body composition, bone metabolism, sexual function, and physical strength in frailty and provides neuroprotection, improves cognitive function, and memory enhancement. DHEA possesses pleiotropic effects and reduced levels of DHEA and DHEA-S may be associated with a host of pathologies; however, the clinical efficacy of DHEA supplementation in ameliorating patho-physiological symptoms remains to be evaluated. Traish AM, Kang HP, Saad F, and Guay AT. Dehydroepiandrosterone (DHEA)-A precursor steroid or an active hormone in human physiology. J Sex Med 2011;8:2960-2982.