PHYSIOLOGICAL-CHANGES IN DEHYDROEPIANDROSTERONE ARE NOT REFLECTED BY SERUM LEVELS OF ACTIVE ANDROGENS AND ESTROGENS BUT OF THEIR METABOLITES - INTRACRINOLOGY

This study analyzes in detail the serum concentration of the active an drogens and estrogens, as well as a series of free and conjugated form s of their precursors and metabolites, after daily application for 2 w eeks of 10 mL 20% dehydroepiandrosterone (DHEA) solution on the skin t o avoid first passage through the liver. In men, DHEA administration c aused 175%, 90%, 200% and 120% increases in the circulating levels of DHEA and its sulfate (DHEA-S), DHEA-fatty acid esters, and androst-5-e ne-3 beta,17 beta-diol, respectively, with a return to basal values 7 days after cessation of the 14-day treatment. Serum androstenedione in creased by approximately 80%, whereas serum testosterone and dihydrote stosterone (DHT) remained unchanged. In parallel with the changes in s erum DHEA, the concentrations of the conjugated metabolites of DHT, na mely androsterone glucuronide, androstane-3 alpha,17 beta-diol-G, and androstane-3 beta,17 beta-diol-G increased by about 75%, 50%, and 75%, respectively, whereas androsterone-sulfate increased 115%. No consist ent change was observed in serum estrone (E-1) or estradiol (E-2) in m en receiving DHEA, whereas serum E-1-sulfate and E-2-sulfate were slig htly and inconsistently increased by about 20%, and serum cortisol and aldosterone concentrations were unaffected by DHEA administration. Al most superimposable results were obtained in women for most steroids e xcept testosterone, which was about 50% increased during DHEA treatmen t. This increase corresponded to about 0.8 nM testosterone, an effect undetectable in men because they already have much higher (similar to 15 nM) basal testosterone levels. In women, the serum levels of the co njugated metabolites of DHT, namely androsterone glucuronide, androsta ne-3 alpha,17 beta-diol-G, androstane-3 beta,17 beta-diol-G, and andro sterone-sulfate were increased by 125%, 140%, 120% and 150%, respectiv ely. The present study demonstrates that the serum concentrations of t estosterone, DHT, E-1, and E-2 are poor indicators of total androgenic and estrogenic activity. However, the esterified metabolites of DHT a ppear as reliable markers of the total androgen pool, because they dir ectly reflect the intracrine formation of androgens in the tissues pos sessing the steroidogenic enzymes required to transform the inactive p recursors DHEA and DHEA-S into DHT. As well demonstrated in women, who synthesize almost all their androgens from DHEA and DHEA-S, supplemen tation with physiological amounts of exogeneous DHEA permits the biosy nthesis of androgens limited to the appropriate target tissues without leakage of significant amounts of active androgens into the circulati on. This local or intracrine biosynthesis and action of androgens elim inates the inappropriate exposure of other tissues to androgens and th us minimizes the risks of undesirable masculinizing or other androgen- related side effects of DHEA.