ANDROSTERONE GLUCURONIDE IS A MARKER OF ADRENAL HYPERANDROGENISM IN HIRSUTE WOMEN

Abstract

Androsterone glucuronide (Andros-G), a dihydrotestosterone metabolite, is present in serum at concentrations at least tenfold greater than those of androstanediol glucuronide. To investigate the significance of serum androsterone glucuronide, we developed a direct radioimmunoassay for this compound and measured its level in normal women, women with mild or severe idiopathic hirsutism (IH), hirsute women with polycystic ovarian syndrome (PCO), and non-hirsute obese women. To determine the source of Andros-G precursors, serum levels were measured before and after selective ovarian suppression with leuprolide, combined ovarian and adrenal suppression with leuprolide and dexamethasone, and adrenal stimulation with ACTH. Androsterone glucuronide levels (nmol/l; mean .+-. SD) were significantly higher (P < 0.025) in women with mild idiopathic hirsutism (IH) (185 .+-. 91), severe IH (173 .+-. 97), and hirsute women with polycystic ovarian syndrome (PCO) (178 .+-. 012) than in normal women (110 .+-. 26). Levels in non-hirsute obese women (64 .+-. 19) were lower than in normal women (P < 0.01). Baseline levels (mean .+-. SEM) in hirsute women given 20 .mu.g/kg/day leuprolide for 5-9 months (171 .+-. 15) were not significantly changed after leuprolide alone (153 .+-. 18), and were decreased after adding dexamethasone (19 .+-. 6; P < 0.001). Andros-G levels did not increase significantly in normal women 60 min after i.v. ACTH (112 .+-. 14 to 126 .+-. 19), but rose in IH (170 .+-. 24 to 216 .+-. 26; P < 0.001) and in PCO (179 .+-. 26 to 238 .+-. 31; P = 0.002). We conclude that Andros-G in women arises primarily from adrenal gland precursors and is elevated in hirsute women as a group. Its levels do not correlate with the severity of hirsutism, or the presence or absence of PCO, but reflect an increased production of adrenal androgens in both IH and PCO.