Abstract
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.
Highlights
Context: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), but the exact origin of hyperandrogenemia remains a matter of debate
We show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk. (J Clin Endocrinol Metab 102: 840–848, 2017)
The origin of androgen excess in PCOS has not been conclusively determined and may differ with phenotype variability, but it is clear that both ovaries and adrenals contribute to increased circulating androgens in affected women
Summary
One hundred fourteen women with PCOS and 49 healthy control subjects underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. PCOS was diagnosed according to the Rotterdam European Society of Human Reproduction and Embryology 2004 criteria, requiring the presence of 2 or more of the following features: oligo/anovulation, clinical signs of hyperandrogenism or biochemical androgen excess, and polycystic ovaries on ultrasound [1]. Healthy control subjects were recruited via local advertisement, with the exclusion of PCOS on clinical and biochemical grounds. This was done by obtaining a menstrual history, by direct questioning regarding clinical features of androgen excess, and by biochemical analysis of serum androgens. Exclusion criteria for the study were as follows: recent glucocorticoid treatment (within 3 months), pregnancy, age younger than 18 or older than 40 years, recent oral contraceptive use (within 3 months), hyperprolactinemia, thyroid disorders, and frank hyperglycemia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
