Normal and elevated 3 alpha-androstanediol glucuronide concentrations in women with various causes of hirsutism and its correlation with degree of hirsutism and androgen levels.

We investigated peripheral androgen metabolic activity in 54 hirsute females (HF) by evaluating the serum 3 alpha-androstanediol glucuronide (3AG) concentration, hirsutism score (HS), and etiology of hirsutism. Based on basal and ACTH-stimulated steroid profiles (1 h post-Cortrosyn, 0.25 mg, i.v. bolus), the causes of hirsutism were determined to be increased adrenal androgen production (greater than 2 SD above normal mean), increased ovarian testosterone (T) production (greater than 2 SD above normal mean basal T of ovarian source only), or idiopathic cause (normal steroid profile). Serum 3AG levels in each group of HF were significantly higher (P less than 0.01-0.001) than those in normal females [normal: 2.9 +/- 0.94 nmol/L (n = 28); HF: increased adrenal androgen production of undefined cause, 7.7 +/- 7.5 nmol/L (n = 14); 21-hydroxylase deficiency, 7.6 +/- 7.4 nmol/L (n = 5); increased ovarian T production 5.5 +/- 3.5 nmol/L (n = 18); idiopathic cause, 5.8 +/- 4.8 nmol/L (n = 17)]. However, normal 3AG levels (less than 5.2 nmol/L) were present in 50-67% of HF in each group. Collectively, 3AG levels in HF correlated significantly (P less than 0.01) with dehydroepiandrosterone (DHEA; r = 0.41) and DHEA sulfate (DS; r = 0.44), while the correlation with androstenedione (r = 0.15) or T (r = 0.19) was not significant. Serum 3AG and adrenal androgen levels decreased in all subjects after dexamethasone treatment (0.5-1 mg at hour of sleep; 2 mg/day for 3-5 days). The correlation between 3AG and HS was significant (r = 0.6-0.74; P less than 0.01-0.001) only in HF with increased adrenal androgen secretion and idiopathic cause, and was not significant (r = 0.42) in HF with increased ovarian T secretion. There was no significant correlation between androgen levels and HS. We conclude that the serum 3AG level was not consistently elevated in HF and did not differ significantly between the various causes. Significant correlations between 3AG and DHEA/DS levels, and the simultaneous decrease in 3AG and adrenal androgens after dexamethasone administration in HF suggest that adrenal androgens contribute significantly to 3AG production. The significant correlation between 3AG and HS in HF with increased adrenal androgen secretion and idiopathic cause indirectly suggests an adrenal androgen contribution to both 3AG production and hirsutism in these HF. The insignificant correlation between 3AG and HS in HF with increased ovarian T secretion may result from a confounding effect of ovarian T on hirsutism.