DHEA

DHEA is synthesized from cholesterol via pregnenolone and 17-hydroxypregnenolone through the action of 17,20-lyase (CYP17A1) in the zona reticularis, under regulation of ACTH. It is largely converted to DHEA-sulfate (DHEA-S) by sulfotransferase (SULT2A1) in the adrenal gland and liver, which increases its stability and serum half-life, making DHEA-S a preferred clinical marker for adrenal androgen output. DHEA/DHEA-S levels rise during adrenarche (ages 6-8) and peak in the mid-20s, then decline steadily with age. Clinically, elevated DHEA-S suggests an adrenal source of androgen excess (e.g., congenital adrenal hyperplasia, adrenal tumor, PCOS with adrenal component), distinguishing it from ovarian/testicular androgen sources where DHEA-S would be normal but testosterone elevated. In congenital adrenal hyperplasia (21-hydroxylase deficiency), precursors including DHEA are shunted into the androgen pathway leading to virilization. DHEA-secreting adrenal tumors can cause rapid-onset virilization in females. DHEA is also sold as an over-the-counter supplement, purported to have anti-aging, athletic performance, and mood benefits, though evidence is limited and it is banned by many athletic organizations as it can be converted to testosterone. In premature adrenarche, elevated DHEA-S causes early pubic hair and body odor without other signs of true puberty (no significant testosterone/estrogen effects like breast development or testicular enlargement), distinguishing it from central precocious puberty.