Pharmacology and therapeutic effects of dehydroepiandrosterone in older subjects

Abstract

Man and higher primates have adrenals that secrete large amounts of dehydroepiandrosterone (DHEA) [prasterone] and its sulphate (DHEAS) [PB 008]. A remarkable feature of plasma DHEAS levels in humans is their great decrease with aging. Researchers have postulated that this age-related decline of DHEAS levels may explain some of the degenerative changes associated with aging. Moreover, administration of DHEA to laboratory animals has demonstrable beneficial effects such as prevention of diabetes mellitus, obesity, cancer, heart disease and positive immunomodulator effects. However, in rodents DHEA(S) circulating levels are so low that it is impossible to detect any significant age-related decrease. Therefore results from rodent experiments are not relevant to human beings. Three mechanisms of action of DHEA(S) have been identified. DHEA and DHEAS are precursors of testosterone and estradiol, DHEAS is a neurosteroid which modulates neuronal excitability via specific interactions with neurotransmitter receptors and DHEA is an activator of calcium-gated potassium channels. Randomised, placebo-controlled clinical trials which included healthy individuals aged 60 years and over treated with (near) physiological doses of DHEA (50-100 mg/day) have yielded very few positive results. Impact of DHEA replacement treatment was assessed on mood, well being, cognitive and sexual functions, bone mass, body composition, vascular risk factors, immune functions and skin. The major limitations of these trials were their short duration (maximum 1 year) and the low number of study participants involved (maximum 280). Many elderly people in western countries take DHEA without medical supervision. In the US, DHEA is even classified as food supplement. At present there is no scientific evidence to recommend DHEA replacement in the elderly. Further studies are needed to form conclusions about the efficacy and the safety of DHEA replacement in elderly, and to better understand the mechanisms of action of DHEA at the molecular and cellular levels.