DHEA replacement

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Wiebke Arlt, MD, Dept of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom

Dehydroepiandrosterone (DHEA) and its sulfate ester are major secretory products of the human adrenal cortex. Serum DHEA concentrations decline with advancing age and DHEA supplementation has been advocated as anti-aging medication. DHEA is converted in vivo into potent sex steroids exhibiting intracrine and endocrine actions dependent on the presence of steroid metabolising enzymes in different tissues. In addition, DHEA acts as a neurosteroid and may also act at specific membrane DHEA receptors. DHEA has multiple beneficial effects in patients with adrenal insufficiency , patients with mood disorders (antidepressive and anxiolytic action) and immunopathies (glucocorticoid sparing effects). However, anti-aging effects have not been consistently demonstrated. Administration of DHEA can be used to study the role of changes in steroid enzyme activity during aging. Preliminary data indicate that the decline in circulating androgens with aging is in part compensated by increased 5 alpha reductase activity in peripheral tissues. In contrast to a widely held belief, DHEAS is not easily back-converted to DHEA and may represent a largely inactive form of DHEA suggesting that peripheral sulfotransferase activity may control the action of DHEA. Accordingly, serum DHEAS is probably not representative of circulating DHEA activity.