The metabolism of dehydroepiandrosterone sulfate and dehydroepiandrosterone

Dehydroepiandrosterone sulfate (DHEAS), one of the major secretory products of the adrenal glands, is cleared very slowly from the circulation with a t1/2 of 13.7 h and a metabolic clearance rate of 15.5 1/day. This slow metabolism is due, largely, to its strong binding to serum albumin, and its renal tubular reabsorption. It is metabolized mainly by hydrolysis to dehydroepiandrosterone (DHEA) and is also converted to androstenedione and testosterone in peripheral tissues. In contrast, DHEA is metabolized much more rapidly with a t1/2 of 60 min, and a metabolic clearance rate of 2050 1/day. Dehydroepiandrosterone is bound to albumin less strongly than is DHEAS. There is conversion of DHEA back to DHEAS as well as conversion to androstenedione and testosterone. When DHEA is given orally, there is a marked increase in circulating DHEAS, greater than the increase in DHEA, and a lesser increase in circulating androgens.