ANDROSTERONE SULFATE - PHYSIOLOGY AND CLINICAL-SIGNIFICANCE IN HIRSUTE WOMEN

Androsterone sulfate (Andros-S) is the most abundant 5alpha-reduced an drogen metabolite in serum. To determine whether this steroid could se rve as a marker of 5alpha-reductase activity, we developed a specific RIA, using tritiated Andros-S to assess procedural losses. Baseline se rum Andros-S levels (mumol/L; mean +/- SEM) in 14 hirsute women (3.0 /-0.4) were not reduced by ovarian suppression with leuprolide (3.0 +/ -0.3), but were decreased by 79% with combined ovarian and adrenal sup pression with leuprolide and dexamethasone. The mean Andros-S level in polycystic ovarian syndrome (3.2 +/- 0.4) and in idiopathic hirsutism (3.5 +/- 0.5) was not significantly different from levels in normal w omen (3.0 +/- 0.5), but were significantly greater than levels in obes e women (1.7 +/- 0.3; P < 0.05). The serum concentrations of Andros-S were about 10-fold greater than those of androsterone glucuronide and 100-fold greater than those of androstanediol glucuronide. Serum Andro s-S concentrations correlated strongly with dehydroepiandrosterone sul fate (R = 0.59; P < 0.001) and to a lesser degree with androstanediol glucuronide and androsterone glucuronide (R = 0.28 and 0.49, respectiv ely). There was a weak correlation with androstenedione levels and the androstenedione response to ACTH (R = 0.38 and 0.34, respectively), a nd no significant correlation with serum testosterone (R = 0.19). The ratio of any of the 5alpha-reduced products (Andros-S, androstanediol glucuronide, and androsterone glucuronide) to precursors (androstenedi one and testosterone) was not increased in hirsute women, suggesting t hat these women did not have a generalized increase in 5alpha-reductas e activity. In conclusion, these results confirm that Andros-S is the most abundant 5alpha-reduced androgen metabolite in serum. It is prima rily, if not exclusively, of adrenal origin in hirsute women. The fact that its levels were not elevated in hirsutism, although those of oth er adrenal androgens and androgen metabolites (androstanediol glucuron ide and androsterone glucuronide) were, suggests that variations in su lfotransferase activity or metabolic clearance of Andros-S may be impo rtant determinants of serum Andros-S levels. Although Andros-S may be a marker of systemic 5alpha-reductase activity, there was no evidence of a generalized increase in 5alpha-reductase activity in hirsute wome n. Andros-S is therefore not recommended as a marker of either adrenal androgen production or of hirsutism.