A review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: is treatment beneficial?

Abstract

Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant steroids in humans. DHEA levels fall with age in men and women, reaching values sometimes as low as 10%-20% of those encountered in young individuals. This age-related decrease suggests an "adrenopause" phenomenon. Studies point toward several potential roles of DHEA, mainly through its hormonal end products, making this decline clinically relevant. Unfortunately, even if positive effects of DHEA on muscle, bone, cardiovascular disease, and sexual function seem rather robust, extremely few studies are large enough and/or long enough for conclusions regarding its effects on aging. Moreover, because it has been publically presented as a "fountain of youth" equivalent, over-the-counter preparations lacking pharmacokinetic and pharmacodynamic data are widely used worldwide. Conceptually, supplementing a pre-hormone is extremely interesting, because it would permit the human organism to adequately use it throughout long periods, increasing or decreasing end products according to his needs. Nevertheless, data on the safety profile of long-term DHEA supplementation are still lacking. In this article, we examine the potential relation between low DHEA levels and well-known age-related diseases, such as sarcopenia, osteoporosis, dementia, sexual disorders, and cardiovascular disease. We also review risks and benefits of existing protocols of DHEA supplementation.

FIG. 1.

Dehydroepiandrosterone (DHEA) and its hormonal end products. Those with intrinsic estrogenic activity are noted in black, those with androgenic activity in light gray, and those with both in dark gray. DHEAS, DHEA sulfate; HSD, hydroxysteroid dehydrogenase; HSOR, hydroxysteroid oxydoreductase; UGT, uridine glucuronosyl transferase; 5-DIOL-S, androst-5-ene-3α,17β-diol sulfate; 5-DIOL, androst-5-ene-3α,17β-diol; 3α-DIOL-G : androstane-3α,17β-diol glucuronide; 3α-DIOL-G, androstane-3α,17β-diol glucuronide; 5-DIOL-FA, androst-5-ene-3α,17β-diol fatty acid. FA, fatty acid.