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, 7α and 7ß DHEA, and 7α and 7ß epiandrosterone derivatives) acting through their specific receptors. These pathways include: nitric oxide synthase activation, modulation of γ-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.

Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients.

INTRODUCTION: 5α-reductase inhibitors (5α-RIs), finasteride and dutasteride, have been approved for treatment of lower urinary tract symptoms, due to benign prostatic hyperplasia, with marked clinical efficacy. Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia, depression, and quality of life remains ill-defined. AIM: The goal of this review is to discuss 5α-RIs therapy, the potential persistent side effects, and the possible mechanisms responsible for these undesirable effects. METHODS: We examined data reported in various clinical studies from the available literature concerning the side effects of finasteride and dutasteride. MAIN OUTCOME MEASURES: Data reported in the literature were reviewed and discussed. Results. Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship. CONCLUSIONS: We suggest discussion with patients on the potential sexual side effects of 5α-RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia.