11-oxygenated C19 steroids are the predominant androgens in polycystic ovary syndrome

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...

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Published in:The journal of clinical endocrinology and metabolism 2017-03, Vol.102 (3), p.840-848
Main Authors: O’Reilly, Michael W, Kempegowda, Punith, Jenkinson, Carl, Taylor, Angela E, Quanson, Jonathan L, Storbeck, Karl-Heinz, Arlt, Wiebke
Format: Article
Language:English
Subjects:
Adult
Androgens
Androgens - metabolism
Androstenedione
Androstenedione - analogs & derivatives
Androstenedione - metabolism
Androstenes - metabolism
Blood Glucose - metabolism
Body mass
Body mass index
Case-Control Studies
Chromatography
Chromatography, Liquid
Clinical s
Dehydroepiandrosterone
Dehydroepiandrosterone - metabolism
Demographics
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
Metabolism
Obesity - complications
Obesity - metabolism
Oxygenation
Polycystic ovary syndrome
Polycystic Ovary Syndrome - complications
Polycystic Ovary Syndrome - metabolism
Scientific imaging
Steroid hormones
Steroids
Tandem Mass Spectrometry
Testosterone
Testosterone - analogs & derivatives
Testosterone - metabolism
Young Adult
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container_title The journal of clinical endocrinology and metabolism
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creator O’Reilly, Michael W
Kempegowda, Punith
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Taylor, Angela E
Quanson, Jonathan L
Storbeck, Karl-Heinz
Arlt, Wiebke
description 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 the androgen excess phenotype in women with PCOS.Methods:114 women with PCOS and 49 healthy controls underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. 24-h urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for calculation of homeostatic model assessment of insulin resistance (HOMA-IR). Baseline demographic data including body mass index were recorded.Results:As expected, serum concentrations of the classic androgens testosterone (p
doi_str_mv 10.1210/jc.2016-3285
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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 the androgen excess phenotype in women with PCOS.Methods:114 women with PCOS and 49 healthy controls underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. 24-h urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for calculation of homeostatic model assessment of insulin resistance (HOMA-IR). Baseline demographic data including body mass index were recorded.Results:As expected, serum concentrations of the classic androgens testosterone (p&lt;0.001), androstenedione (p&lt;0.001), and DHEA (p&lt;0.01) were significantly increased in PCOS. Mirroring this, serum concentrations of the 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone were all significantly higher in PCOS women than controls, as was the urinary excretion of the 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in PCOS compared to controls [53.0% (IQR 48.7-60.3) vs. 44.0% (IQR 32.9-54.9), p&lt;0.0001]. Both obese (n=51) and non-obese (n=63) PCOS patients had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance.Conclusions:For the first time, we show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2016-3285</identifier><identifier>PMID: 27901631</identifier><language>eng</language><publisher>Washington, DC: Endocrine Society</publisher><subject>Adult ; Androgens ; Androgens - metabolism ; Androstenedione ; Androstenedione - analogs &amp; derivatives ; Androstenedione - metabolism ; Androstenes - metabolism ; Blood Glucose - metabolism ; Body mass ; Body mass index ; Case-Control Studies ; Chromatography ; Chromatography, Liquid ; Clinical s ; Dehydroepiandrosterone ; Dehydroepiandrosterone - metabolism ; Demographics ; 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 ; Metabolism ; Obesity - complications ; Obesity - metabolism ; Oxygenation ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - complications ; Polycystic Ovary Syndrome - metabolism ; Scientific imaging ; Steroid hormones ; Steroids ; Tandem Mass Spectrometry ; Testosterone ; Testosterone - analogs &amp; derivatives ; Testosterone - metabolism ; Young Adult</subject><ispartof>The journal of clinical endocrinology and metabolism, 2017-03, Vol.102 (3), p.840-848</ispartof><rights>Copyright © 2016 by the Endocrine Society</rights><rights>Copyright © Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c554t-b96c9645ed6cc4747ed4ba27869a625a0743cc02eec92a493197029f2032c7003</citedby><cites>FETCH-LOGICAL-c554t-b96c9645ed6cc4747ed4ba27869a625a0743cc02eec92a493197029f2032c7003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27901631$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>O’Reilly, Michael W</creatorcontrib><creatorcontrib>Kempegowda, Punith</creatorcontrib><creatorcontrib>Jenkinson, Carl</creatorcontrib><creatorcontrib>Taylor, Angela E</creatorcontrib><creatorcontrib>Quanson, Jonathan L</creatorcontrib><creatorcontrib>Storbeck, Karl-Heinz</creatorcontrib><creatorcontrib>Arlt, Wiebke</creatorcontrib><title>11-oxygenated C19 steroids are the predominant androgens in polycystic ovary syndrome</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>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 the androgen excess phenotype in women with PCOS.Methods:114 women with PCOS and 49 healthy controls underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. 24-h urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for calculation of homeostatic model assessment of insulin resistance (HOMA-IR). Baseline demographic data including body mass index were recorded.Results:As expected, serum concentrations of the classic androgens testosterone (p&lt;0.001), androstenedione (p&lt;0.001), and DHEA (p&lt;0.01) were significantly increased in PCOS. Mirroring this, serum concentrations of the 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone were all significantly higher in PCOS women than controls, as was the urinary excretion of the 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in PCOS compared to controls [53.0% (IQR 48.7-60.3) vs. 44.0% (IQR 32.9-54.9), p&lt;0.0001]. Both obese (n=51) and non-obese (n=63) PCOS patients had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance.Conclusions:For the first time, we show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk.</description><subject>Adult</subject><subject>Androgens</subject><subject>Androgens - metabolism</subject><subject>Androstenedione</subject><subject>Androstenedione - analogs &amp; derivatives</subject><subject>Androstenedione - metabolism</subject><subject>Androstenes - metabolism</subject><subject>Blood Glucose - metabolism</subject><subject>Body mass</subject><subject>Body mass index</subject><subject>Case-Control Studies</subject><subject>Chromatography</subject><subject>Chromatography, Liquid</subject><subject>Clinical s</subject><subject>Dehydroepiandrosterone</subject><subject>Dehydroepiandrosterone - metabolism</subject><subject>Demographics</subject><subject>Excretion</subject><subject>Female</subject><subject>Gas chromatography</subject><subject>Gas Chromatography-Mass Spectrometry</subject><subject>Humans</subject><subject>Hydroxytestosterones - metabolism</subject><subject>Hyperandrogenism - complications</subject><subject>Hyperandrogenism - metabolism</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin Resistance</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Metabolism</subject><subject>Obesity - complications</subject><subject>Obesity - metabolism</subject><subject>Oxygenation</subject><subject>Polycystic ovary syndrome</subject><subject>Polycystic Ovary Syndrome - complications</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Scientific imaging</subject><subject>Steroid hormones</subject><subject>Steroids</subject><subject>Tandem Mass Spectrometry</subject><subject>Testosterone</subject><subject>Testosterone - analogs &amp; 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Kempegowda, Punith ; Jenkinson, Carl ; Taylor, Angela E ; Quanson, Jonathan L ; Storbeck, Karl-Heinz ; Arlt, Wiebke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c554t-b96c9645ed6cc4747ed4ba27869a625a0743cc02eec92a493197029f2032c7003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Androgens</topic><topic>Androgens - metabolism</topic><topic>Androstenedione</topic><topic>Androstenedione - analogs &amp; derivatives</topic><topic>Androstenedione - metabolism</topic><topic>Androstenes - metabolism</topic><topic>Blood Glucose - metabolism</topic><topic>Body mass</topic><topic>Body mass index</topic><topic>Case-Control Studies</topic><topic>Chromatography</topic><topic>Chromatography, Liquid</topic><topic>Clinical s</topic><topic>Dehydroepiandrosterone</topic><topic>Dehydroepiandrosterone - metabolism</topic><topic>Demographics</topic><topic>Excretion</topic><topic>Female</topic><topic>Gas chromatography</topic><topic>Gas Chromatography-Mass Spectrometry</topic><topic>Humans</topic><topic>Hydroxytestosterones - metabolism</topic><topic>Hyperandrogenism - complications</topic><topic>Hyperandrogenism - metabolism</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin Resistance</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Metabolism</topic><topic>Obesity - complications</topic><topic>Obesity - metabolism</topic><topic>Oxygenation</topic><topic>Polycystic ovary syndrome</topic><topic>Polycystic Ovary Syndrome - complications</topic><topic>Polycystic Ovary Syndrome - metabolism</topic><topic>Scientific imaging</topic><topic>Steroid hormones</topic><topic>Steroids</topic><topic>Tandem Mass Spectrometry</topic><topic>Testosterone</topic><topic>Testosterone - analogs &amp; derivatives</topic><topic>Testosterone - metabolism</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>O’Reilly, Michael W</creatorcontrib><creatorcontrib>Kempegowda, Punith</creatorcontrib><creatorcontrib>Jenkinson, Carl</creatorcontrib><creatorcontrib>Taylor, Angela E</creatorcontrib><creatorcontrib>Quanson, Jonathan L</creatorcontrib><creatorcontrib>Storbeck, Karl-Heinz</creatorcontrib><creatorcontrib>Arlt, Wiebke</creatorcontrib><collection>Open Access: Oxford University Press Open Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>ProQuest Health &amp; 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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 the androgen excess phenotype in women with PCOS.Methods:114 women with PCOS and 49 healthy controls underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. 24-h urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for calculation of homeostatic model assessment of insulin resistance (HOMA-IR). Baseline demographic data including body mass index were recorded.Results:As expected, serum concentrations of the classic androgens testosterone (p&lt;0.001), androstenedione (p&lt;0.001), and DHEA (p&lt;0.01) were significantly increased in PCOS. Mirroring this, serum concentrations of the 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone were all significantly higher in PCOS women than controls, as was the urinary excretion of the 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in PCOS compared to controls [53.0% (IQR 48.7-60.3) vs. 44.0% (IQR 32.9-54.9), p&lt;0.0001]. Both obese (n=51) and non-obese (n=63) PCOS patients had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance.Conclusions:For the first time, we show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk.</abstract><cop>Washington, DC</cop><pub>Endocrine Society</pub><pmid>27901631</pmid><doi>10.1210/jc.2016-3285</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Androgens
Androgens - metabolism
Androstenedione
Androstenedione - analogs & derivatives
Androstenedione - metabolism
Androstenes - metabolism
Blood Glucose - metabolism
Body mass
Body mass index
Case-Control Studies
Chromatography
Chromatography, Liquid
Clinical s
Dehydroepiandrosterone
Dehydroepiandrosterone - metabolism
Demographics
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
Metabolism
Obesity - complications
Obesity - metabolism
Oxygenation
Polycystic ovary syndrome
Polycystic Ovary Syndrome - complications
Polycystic Ovary Syndrome - metabolism
Scientific imaging
Steroid hormones
Steroids
Tandem Mass Spectrometry
Testosterone
Testosterone - analogs & derivatives
Testosterone - metabolism
Young Adult
title 11-oxygenated C19 steroids are the predominant androgens in polycystic ovary syndrome
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