title: Assessment of androgen concentration in women: liquid chromatography-tandem mass spectrometry and extraction RIA show comparable results.
abstract: OBJECTIVE
  The measurement of serum testosterone in women is challenging due to lack of trueness, precision, and sensitivity of various available testosterone assays. Accurate assessment of testosterone in women is crucial especially in conditions associated with alleged over- or under-production of testosterone, such as in polycystic ovary syndrome (PCOS) or primary ovarian insufficiency (POI). The aim of this study was to measure and compare androgen concentrations in women with PCOS, POI, and female controls and to evaluate the performance of extraction RIA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in these women.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Carefully phenotyped women with POI (n=208) or PCOS (n=200) and 45 healthy, regularly cyclic female controls were included. Method comparison analyses were performed for total testosterone, androstenedione (AD), and DHEA, as measured by LC-MS/MS and extraction RIA.
  
  
  RESULTS
  All androgen levels were significantly elevated in women with PCOS compared with POI patients (P<0.05) and controls (P<0.05). Women with POI presented with similar androgen concentrations as controls, except for AD. Compared with measurements by extraction RIA, testosterone, DHEA, and AD concentrations measured by LC-MS/MS were systematically lower. However, using extraction RIA and LC-MS/MS, testosterone, DHEA, and AD measurements were shown to have good agreement as assessed by Bland-Altman analysis and intraclass correlation coefficient: 0.95 (95% confidence interval 0.94-0.91), 0.83 (0.79-0.86), and 0.96 (0.95-0.97) respectively.
  
  
  CONCLUSIONS
  LC-MS/MS, compared with a labor-intensive extraction RIA, shows good precision, sensitivity, and high accuracy for measuring female testosterone, DHEA, and AD concentrations under various clinical conditions. LC-MS/MS, therefore, represents a convenient and reliable assay for both clinical and research purposes, where androgen measurement in women is required.
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, The Netherlands.
authors.forename: Femi
authors.initials: F
authors.lastname: Janse
authors.forename: Martinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: Angelique J
authors.initials: AJ
authors.lastname: Goverde
authors.forename: Eef G W M
authors.initials: EG
authors.lastname: Lentjes
authors.forename: Annemieke
authors.initials: A
authors.lastname: Hoek
authors.forename: Cornelius B
authors.initials: CB
authors.lastname: Lambalk
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Hickey
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Norman
mesh_terms: D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011863:Radioimmunoassay / Q000379:methods / Q000592:standards; D011897:Random Allocation; D053719:Tandem Mass Spectrometry / Q000379:methods / Q000592:standards*; D055815:Young Adult
chemical_list: D000728:Androgens; D015415:Biomarkers