Evidence for the Importance of Peripheral Tissue Events in the Development of Hirsutism in Polycystic Ovary Syndrome*

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Abstract
Hirsutism can occur in the presence of normal or near normal levels of serum testosterone, unbound testosterone (uT), dehydroepiandrostene sulfate, androstenedione, and dihydrotestosterone. However, we have found that serum androstanediol glucuronide (3α-diol G) is markedly increased in idiopathic hirsutism and it serves as an excellent marker of peripheral androgen metabolism and action. In the present work, we studied 12 hirsute (H) and 12 nonhirsute (NH) patients with polycystic ovary syndrome (PCO) and 13 age and weight matched controls in order to determine if differences in sex steroid levels or peripheral tissue androgen events were associated with hirsutism. Serum unbound estradiol levels and LHFSHratios were similar in both groups of women with PCO, and both were significantly higher than levels in controls (P < 0.05). Whereas serum testosterone, uT, and androstenedione were elevated in both H-PCO and NH-PCO patients compared to controls, the levels in these two groups were similar. Serum dehydroepiandrostene sulfate was higher in PCO patients comparedcompared to controls, but H-PCO patients had slightly higher levels than NH-PCO patients. Serum Δ5-androstenediol was also slightly higher in H-PCO compared to NH-PCO patients. Dihydrotestosterone was normal and unconjugated; 3α-diol was higher than normal in both groups of patients with PCO, although H-PCO patients had higher levels than NH-PCO patients. Compared to these relatively minor changes between the PCO patient groups, serum 3α-diol G was markedly elevated in H-PCO patients (approximately 10-fold), yet normal in NHPCO patients (P < 0.01). The ratios of serum 3α-diol G-uT were similar in NH-PCO patients and controls, but were elevated in H-PCO patients (P < 0.01). These data indicate that: 1) women with PCO have increased circulating androgen levels regardless of the presence or absence of hirsutism; and 2) the presence of hirsutism is not only a function of circulating androgen levels, but may also be determined by events in peripheral tissues.