Abstract
Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant steroids in human circulation but only recently received the attention of the scientific community. Biosynthesis of DHEA occurs in the adrenal zona reticularis and the gonads and is catalyzed by P450c17. In humans, DHEA is the crucial precursor for all sex steroids and exhibits indirect action after peripheral conversion to androgens and estrogens. In addition, DHEA can exert direct effects via interaction with neurotransmitter receptors in the brain. These two mechanisms of action explain most of the observed clinical effects: androgenic and estrogenic effects on lipids, skin, bone, skin and body composition; and neurosteroidal effects on mood and libido. However, neurosteroidal effects of DHEA replacement are only seen in patients with a pathologic loss of DHEA production (ie, adrenal insufficiency) and patients with impaired well-being and sexuality. Volunteers with normal well-being do not experience further improvements after DHEA administration. Future prospects of DHEA replacement involve its establishment as part of the standard replacement therapy in adrenal insufficiency and the investigation of potential benefits in patients receiving chronic glucocorticoid treatment and in women with androgen deficiency.
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