Context:Androgen excess is a defining feature of polycystic ovary syndrome (PCOS),
but the exact origin of hyperandrogenemia remains a matter of debate. Recent
studies have highlighted the importance of the 11-oxygenated C19 steroid
pathway to androgen metabolism in humans. In this study, we analyzed the
contribution of 11-oxygenated androgens to androgen excess in women with
PCOS.Methods:One hundred fourteen women with PCOS and 49 healthy control subjects
underwent measurement of serum androgens by liquid chromatography-tandem
mass spectrometry. Twenty-four–hour urinary androgen excretion was
analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and
glucose were measured for homeostatic model assessment of insulin
resistance. Baseline demographic data, including body mass index, were
recorded.Results:As expected, serum concentrations of the classic androgens testosterone
(P < 0.001), androstenedione (P
< 0.001), and dehydroepiandrosterone (P <
0.01) were significantly increased in PCOS. Mirroring this, serum
11-oxygenated androgens 11β-hydroxyandrostenedione,
11-ketoandrostenedione, 11β-hydroxytestosterone, and
11-ketotestosterone were significantly higher in PCOS than in control
subjects, as was the urinary 11-oxygenated androgen metabolite
11β-hydroxyandrosterone. The proportionate
contribution of 11-oxygenated to total serum androgens was significantly
higher in patients with PCOS compared with control subjects [53.0%
(interquartile range, 48.7 to 60.3) vs 44.0% (interquartile
range, 32.9 to 54.9); P < 0.0001]. Obese (n = 51)
and nonobese (n = 63) patients with PCOS had significantly increased
11-oxygenated androgens. Serum
11β-hydroxyandrostenedione and
11-ketoandrostenedione correlated significantly with markers of insulin
resistance.Conclusions:We show that 11-oxygenated androgens represent the majority of circulating
androgens in women with PCOS, with close correlation to markers of metabolic
risk.
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