title: Defining hyperandrogenism in polycystic ovary syndrome: measurement of testosterone and androstenedione by liquid chromatography-tandem mass spectrometry and analysis by receiver operator characteristic plots.
abstract: OBJECTIVE
  Hyperandrogenism is one of the diagnostic criteria for the polycystic ovary syndrome (PCOS) despite no agreed definition of hyperandrogenism. In part, this is due to the quality of testosterone immunoassays. We have developed liquid chromatography-tandem mass spectrometry methods for analysing testosterone and androstenedione (Ad) to study their reference ranges and diagnostic utility in PCOS.
  
  
  METHODS
  A consecutive series of 122 women attending a reproductive medicine clinic.
  
  
  METHODS
  Blood samples were taken during the early follicular phase for measurement of LH, FSH, oestradiol, Ad, testosterone and sex hormone-binding globulin (SHBG). Retrospective case note analysis was used to determine the clinical features and ultrasound findings.
  
  
  RESULTS
  The incidence of PCOS was 13.9%. The reference interval for testosterone was <1.8 nmol/l and for Ad was 1.4-7.4 nmol/l. There were significant differences in total testosterone (P=0.001), Ad (P<0.05) and free androgen index (FAI; P<0.0001) between the women with and without PCOS. Diagnostic performance using receiver operator characteristic plots showed area under the curve (AUC) for FAI 0.81, testosterone 0.75 and Ad 0.66. The AUC for the LH:FSH ratio was 0.72.
  
  
  CONCLUSIONS
  Our analysis of a consecutive series of women attending a reproductive clinic has provided an appropriate series on which to construct reference ranges for key androgens in women. Secondly, it has allowed us to conclude that early follicular serum testosterone measured using tandem mass spectrometry, FAI and the LH:FSH ratio are valuable laboratory tests in the diagnosis of PCOS.
authors.affiliation: Department of Clinical Biochemistry, Leeds General Infirmary, Leeds LS1 3EX, UK. julian.barth@leedsth.nhs.uk
authors.forename: Julian H
authors.initials: JH
authors.lastname: Barth
authors.forename: Helen P
authors.initials: HP
authors.lastname: Field
authors.forename: Ephia
authors.initials: E
authors.lastname: Yasmin
authors.forename: Adam H
authors.initials: AH
authors.lastname: Balen
mesh_terms: D000328:Adult; D000735:Androstenedione / Q000097:blood*; D019540:Area Under Curve; D002853:Chromatography, Liquid; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood* / Q000150:complications; D007986:Luteinizing Hormone / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000150:complications; D012372:ROC Curve; D012016:Reference Values; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000097:blood*
chemical_list: D013739:Testosterone; D000735:Androstenedione; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone