title: Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione.
abstract: BACKGROUND
  Polycystic ovary syndrome (PCOS) is a triad of anovulation, insulin resistance, and hyperandrogenism. Androgen excess may correlate with metabolic risk and PCOS consensus criteria define androgen excess on the basis of serum T. Here we studied the utility of the androgen precursor serum androstenedione (A) in conjunction with serum T for predicting metabolic dysfunction in PCOS.
  
  
  METHODS
  Eighty-six PCOS patients fulfilling Rotterdam diagnostic consensus criteria and 43 age- and body mass index-matched controls underwent measurement of serum androgens by tandem mass spectrometry and an oral glucose tolerance test with homeostatic model assessment of insulin resistance and insulin sensitivity index calculation. We analyzed 24-hour urine androgen excretion by gas chromatography/mass spectrometry.
  
  
  RESULTS
  PCOS patients had higher levels of serum androgens and urinary androgen metabolites than controls (all P < .001). Within the PCOS cohort, both serum A and T were positively correlated with the free androgen index (T × 100/SHBG) and total androgen metabolite excretion (all P < .001). All subjects with T above the normal reference range [high T (HT)] also had high A (HA/HT group, n = 56). However, the remaining 30 patients had normal T levels, either in the presence of HA (HA/NT; n = 20) or normal A (NA/NT; n = 10). The groups did not differ in age or BMI. The HA/HT and HA/NT groups had higher total androgen excretion than NA/NT (P < .01 and P < .05, respectively). Multiple linear regression showed a strong negative association between serum androstenedione and insulin sensitivity. The incidence of dysglycemia according to an oral glucose tolerance test increased with the severity of androgen phenotype (NA/NT, 0%; HA/NT, 14%; HA/HT, 25%, P = .03).
  
  
  CONCLUSIONS
  Simultaneous measurement of serum T and A represents a useful tool for predicting metabolic risk in PCOS women. HA levels are a sensitive indicator of PCOS-related androgen excess.
authors.affiliation: Centre for Endocrinology, Diabetes, and Metabolism (M.W.O., A.E.T., B.A.H., R.K.C., P.M.S., J.W.T., W.A.), School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Department of Nuclear Medicine (N.J.C.), University Hospitals Birmingham, Edgbaston, and National Institute of Health Research/Wellcome Trust Clinical Research Facility (F.C.), University Hospitals Birmingham National Health Service Foundation Trust, Birmingham B15 2TH, United Kingdom; and University of Leeds (P.M.S.), Leeds, LS2 9NL, United Kingdom.
authors.forename: Michael W
authors.initials: MW
authors.lastname: O'Reilly
authors.forename: Angela E
authors.initials: AE
authors.lastname: Taylor
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Crabtree
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Hughes
authors.forename: Farfia
authors.initials: F
authors.lastname: Capper
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Crowley
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Tomlinson
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood / Q000652:urine; D000735:Androstenedione / Q000097:blood* / Q000652:urine; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: D000728:Androgens; D000735:Androstenedione