dehydroepiandrosterone

Dehydroepiandrosterone (DHEA) is a steroid hormone produced mainly by the adrenal cortex, with smaller amounts from the gonads and brain. In the blood it exists largely as the sulfated form DHEA-S, which is abundant and long-lasting; DHEA itself serves as a precursor to active androgens and estrogens, with production stimulated by ACTH and decreasing with age.

Biosynthesis proceeds from cholesterol to pregnenolone, then to DHEA via CYP17A1 in the adrenal zona reticularis. DHEA can be converted to androstenedione and then to testosterone, or to estrogens via aromatase. DHEA-S is produced by sulfotransferases and reflects the circulating reservoir; tissue desulfation yields DHEA.

Physiological role: DHEA is a weak androgen and estrogen precursor. It contributes to bone, immune, metabolic, and possibly mood and cognitive functions, but clear physiological effects are difficult to establish. Circulating DHEA levels decline with age, which has spurred interest in potential anti-aging benefits, though robust clinical evidence is lacking.

Clinical use and safety: DHEA is available as an over-the-counter supplement in many regions but is not approved as a drug for aging or most other indications. Trials have yielded mixed results for adrenal function, menopausal symptoms, cognition, and mood. Long-term high-dose use may cause acne, hirsutism, lipid changes, or liver injury; there are potential interactions with various medications. Use should be discussed with a healthcare professional, and it is generally avoided in pregnancy or lactation.

Measurement: Serum DHEA and DHEA-S are used to assess adrenal function; DHEA-S is more stable and often preferred for routine testing. Levels vary with age, sex, and assay method.