2. Academic Validation
  3. 11-Oxygenated C19 Steroids Are the Predominant Androgens in Polycystic Ovary Syndrome

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

  • J Clin Endocrinol Metab. 2017 Mar 1;102(3):840-848. doi: 10.1210/jc.2016-3285.
Michael W O'Reilly 1 2,  Punith Kempegowda 1 2,  Carl Jenkinson 1 2,  Angela E Taylor 1 2,  Jonathan L Quanson 3,  Karl-Heinz Storbeck 3,  Wiebke Arlt 1 2 4
Affiliations

Affiliations

  • 1 Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
  • 2 Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Edgbaston, Birmingham B15 2TH, United Kingdom.
  • 3 Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa; and.
  • 4 National Institute of Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University Hospital Birmingham, NHS Foundation Trust, Birmingham B15 2GW, United Kingdom.
PMID: 27901631 DOI: 10.1210/jc.2016-3285
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.

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