dehydroepiandrosterone
Summary
Dehydroepiandrosterone (DHEA) is a weak androgen steroid hormone produced primarily by the zona reticularis of the adrenal cortex, serving as a precursor for both androgens and estrogens. It is the most abundant circulating steroid hormone in humans and is often measured (along with DHEA-sulfate) to assess adrenal androgen production, particularly in the workup of hyperandrogenism.
Detail
DHEA is synthesized from cholesterol via pregnenolone in the adrenal cortex (zona reticularis), with a smaller contribution from the gonads and brain. It is converted to DHEA-sulfate (DHEA-S) by sulfotransferase (mainly in the adrenal gland and liver), which has a longer half-life and is the more stable form used clinically for measurement. DHEA/DHEA-S serve as precursors that peripheral tissues convert into more potent androgens (testosterone, androstenedione) and estrogens (estrone, estradiol) via peripheral steroidogenic enzymes.
Clinical significance: - Adrenarche: DHEA/DHEA-S rise during adrenarche (ages 6-8), contributing to pubarche, axillary hair, and body odor, independent of gonadarche/HPG axis activation. - Congenital adrenal hyperplasia (CAH): In 21-hydroxylase deficiency, precursors are shunted toward androgen synthesis, though DHEA-S is more specifically elevated in 3β-hydroxysteroid dehydrogenase deficiency. - Adrenal tumors: Markedly elevated DHEA-S suggests an adrenal source of androgen excess (adrenal tumor or hyperplasia) versus ovarian source (e.g., PCOS, which shows more modestly elevated DHEA-S with elevated testosterone). - PCOS: DHEA-S may be mildly elevated, reflecting adrenal contribution to hyperandrogenism. - Aging: DHEA levels decline with age ("adrenopause"), leading to interest in DHEA supplementation for anti-aging, though evidence for benefit is limited. - Cushing syndrome differentiation: Low DHEA-S with high cortisol suggests an adrenal adenoma producing cortisol alone; adrenal carcinomas often produce both cortisol and DHEA-S.
DHEA is used therapeutically in some cases of adrenal insufficiency to improve well-being and libido, and it is available as an over-the-counter supplement, though its efficacy for various claimed benefits (anti-aging, bodybuilding) is not well substantiated by rigorous evidence.
Sources
- Guyton and Hall Textbook of Medical Physiology
- Williams Textbook of Endocrinology
- First Aid for the USMLE Step 1
- UpToDate: Adrenal androgens and androgen precursors
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