title: 11-Oxygenated C19 Steroids Are the Predominant Androgens in Polycystic Ovary Syndrome.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  We show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk.
authors.affiliation: Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.|Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Edgbaston, Birmingham B15 2TH, United Kingdom.
authors.forename: Michael W
authors.initials: MW
authors.lastname: O'Reilly
authors.affiliation: Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.|Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Edgbaston, Birmingham B15 2TH, United Kingdom.
authors.forename: Punith
authors.initials: P
authors.lastname: Kempegowda
authors.affiliation: Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.|Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Edgbaston, Birmingham B15 2TH, United Kingdom.
authors.forename: Carl
authors.initials: C
authors.lastname: Jenkinson
authors.affiliation: Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.|Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Edgbaston, Birmingham B15 2TH, United Kingdom.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Taylor
authors.affiliation: Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa; and.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Quanson
authors.affiliation: Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa; and.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Storbeck
authors.affiliation: Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.|Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Edgbaston, Birmingham B15 2TH, United Kingdom.|National Institute of Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University Hospital Birmingham, NHS Foundation Trust, Birmingham B15 2GW, United Kingdom.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
mesh_terms: D000328:Adult; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000031:analogs & derivatives / Q000378:metabolism; D000736:Androstenes / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003687:Dehydroepiandrosterone / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006915:Hydroxytestosterones / Q000378:metabolism; D017588:Hyperandrogenism / Q000150:complications / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000031:analogs & derivatives / Q000378:metabolism; D055815:Young Adult
chemical_list: D000728:Androgens; D000736:Androstenes; D001786:Blood Glucose; D006915:Hydroxytestosterones; D007328:Insulin; C037914:11-hydroxytestosterone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; C003582:11-hydroxyandrostenedione; C011657:adrenosterone; C003600:11-ketotestosterone