Dehydroepiandrosterone (DHEA; androstenolone; 3ß-hydroxy-5-androsten-17-one) is a steroid hormone produced principally in the adrenal cortex.   In men, it is estimated that 10-25% of the circulating DHEA is secreted by the testes. (1)  DHEA and its sulfated analog DHEA-S serve primarily as precursors that circulate to peripheral tissues, where they are converted to androgens and estrogens. (1,2)  This allows androgens and estrogens to be delivered to the appropriate tissues without leakage of significant amounts into the circulation. (3,4,5)   In addition to serving as a precursor for other steroid hormones, DHEA is also believed to have some physiological properties of its own. It is known to have anti-glucocorticoid, anti-oxidant, anti-inflammatory, and immunomodulatory effects. (1,5)  The mechanisms of these effects are not well understood and currently under investigation. (5,6,7)  Circulating levels of DHEA peak around the age of 20 to 30, then decline to only 20-30% of peak level by the age of 70 to 80; it has been explored as a marker of aging and for possible anti-aging therapeutic uses. Low levels have been associated with a range of diseases. (1,5) DHEA is also produced in the brain, where is serves as a protective neurosteroid. (8,9) Like cortisol, DHEA synthesis in the adrenal gland is affected by HPA axis activity and the release of ACTH, and DHEA levels increase in response to stress. (10)  Differences in the secretion of the two hormones can exist, however, and changes in the ratio of cortisol to DHEA have been observed in connection with various disorders, including depression, psychiatric conditions,  and HIV infection. (11,12,13,14)  DHEA exhibits a diurnal rhythm synchronized with cortisol, with highest values in the morning and a nadir in the late evening. (15) In blood DHEA is only weakly bound to albumin or sex hormone binding globulin (SHBG). (16,17)  Unbound DHEA enters saliva from blood via intracellular mechanisms, and the serum-saliva correlation is high. (18,19)