11-Oxygenated C19 Steroids Are the Predominant Androgens in Polycystic Ovary Syndrome

• Published in: The journal of clinical endocrinology and metabolism Vol. 102; no. 3; pp. 840 - 848
• Main Authors: O’Reilly, Michael W., Kempegowda, Punith, Jenkinson, Carl, Taylor, Angela E., Quanson, Jonathan L., Storbeck, Karl-Heinz, Arlt, Wiebke
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.03.2017; Oxford University Press
• Subjects: Adult; Androgens; Androgens - metabolism; Androstenedione; Androstenedione - analogs & derivatives; Androstenedione - metabolism; Androstenes - metabolism; Blood Glucose - metabolism; Body mass index; Case-Control Studies; Chromatography; Chromatography, Liquid; Clinical s; Dehydroepiandrosterone; Dehydroepiandrosterone - metabolism; Excretion; Female; Gas chromatography; Gas Chromatography-Mass Spectrometry; Humans; Hydroxytestosterones - metabolism; Hyperandrogenism - complications; Hyperandrogenism - metabolism; Insulin; Insulin - metabolism; Insulin Resistance; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Obesity - complications; Obesity - metabolism; Ovaries; Polycystic ovary syndrome; Polycystic Ovary Syndrome - complications; Polycystic Ovary Syndrome - metabolism; Scientific imaging; Steroid hormones; Tandem Mass Spectrometry; Testosterone; Testosterone - analogs & derivatives; Testosterone - metabolism; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2016-3285

We analyzed the androgen metabolome in women with polycystic ovary syndrome by mass spectrometry, revealing that 11-oxygenated androgens represent the majority of circulating androgen excess.AbstractContext: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.