DHEA

Dehydroepiandrosterone (DHEA) is the major steroid produced by the adrenal zona reticularis, and its secretion declines with ageing in contrast to cortisol and aldosterone. ^[1] DHEA is the most abundant steroid hormone in primates, predominantly synthesised in the adrenal cortex, and circulates together with its sulfate ester DHEAS. ^[2] DHEA and DHEAS are immediate androgen precursors that are better considered pro-androgens, since neither binds the androgen receptor directly. ^[3]

DHEA exhibits its action mainly by conversion to sex steroids and additionally has neurosteroidal properties, acting via specific binding sites on endothelial cells. ^[1] Adrenarche is the maturational increase in adrenal androgen production in early childhood, best indexed by the rise in dehydroepiandrosterone sulfate (DHEAS). ^[4] A characteristic curve of rising and then declining DHEA synthesis occurs across life, and decreased DHEA levels accompany adrenal insufficiency, severe systemic disease, acute stress, and anorexia. ^[2] DHEA is an adrenal precursor from which peripheral tissues locally synthesize most bioactive testosterone and its downstream steroids, an intracrine contribution that serum-centric testosterone replacement therapy guidelines fail to account for ^[5]