title: Performance of mass spectrometry steroid profiling for diagnosis of polycystic ovary syndrome.
abstract: How well does multi-analyte steroid mass spectrometry (MS) profiling classify women with and without polycystic ovary syndrome (PCOS)?
  
  
  
  Our liquid chromatography MS (LC-MS) steroid profiling only minimally improves discrimination of women with and without PCOS compared with a direct testosterone immunoassay (T_IA) and the free androgen index (FAI).
  
  
  
  Blood testosterone measured by direct (non-extraction) immunoassay overlaps between women with and without PCOS. Multi-analyte MS provides greater specificity and accuracy for steroid measurement so might improve the classification.
  
  
  
  An observational, cross-sectional study of women with PCOS (n = 152) defined by Rotterdam criteria and matched non-PCOS (n = 45) control women was conducted.
  
  
  
  Serum steroid profiles of testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione (A4), estradiol (E2), estrone (E1), 17 hydroxy progesterone (17OHP4), progesterone (P4) and cortisol were measured by LC-MS; T_IA and sex hormone binding globulin were measured by immunoassay; and FAI, calculated free testosterone (cFT) and total androgen index (TAI) were calculated. Classification was based on logistic regression with corresponding univariate and multivariate C-statistics.
  
  
  
  Serum testosterone by immunoassay demonstrated levels more than 100% higher than that measured by LC-MS. Compared with the controls, women with PCOS had higher serum T, DHEA, A4, TAI, T_IA, cFT, FAI and E2but not serum DHT, E1, P4, 17OHP4or cortisol. Univariate C-statistics were highest for FAI (0.89) and T_IA (0.82) compared with other androgens (T [0.72], DHT [0.40]), pro-androgens (A4[0.74], DHEA[0.71]) or derivatives (cFT [0.75], TAI [0.60]). For all multivariate models, the overall correct predictions (81-86%) featured high sensitivity (92-96%) but low specificity (28-43%). and substituting LC-MS steroid measurements for T_IA and FAI produced only minimal improvements in classification.
  
  
  
  The study cohort is limited in size and only unconjugated steroids were measured.
  
  
  
  Multi-analyte steroid profiling of unconjugated circulating steroids provides only limited improvement on direct T_IA in classifying women with and without PCOS.
  
  
  
  None.
  
  
  
  N/A.
authors.affiliation: ANZAC Research Institute, University of Sydney, Concord Hospital, NSW 2139, Australia djh@anzac.edu.au.
authors.forename: D J
authors.initials: DJ
authors.lastname: Handelsman
authors.affiliation: Monash Centre for Health Research Implementation, School of Public Health and Preventative Medicine, Monash University, Melbourne 3004, Australia.
authors.forename: H J
authors.initials: HJ
authors.lastname: Teede
authors.affiliation: ANZAC Research Institute, University of Sydney, Concord Hospital, NSW 2139, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Desai
authors.affiliation: The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide South Australia, Australia.
authors.forename: R J
authors.initials: RJ
authors.lastname: Norman
authors.affiliation: Monash Centre for Health Research Implementation, School of Public Health and Preventative Medicine, Monash University, Melbourne 3004, Australia.|The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide South Australia, Australia.
authors.forename: L J
authors.initials: LJ
authors.lastname: Moran
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood*; D003430:Cross-Sectional Studies; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007118:Immunoassay; D013058:Mass Spectrometry / Q000379:methods*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000175:diagnosis*; D011372:Progestins / Q000097:blood*
chemical_list: D000728:Androgens; D004967:Estrogens; D011372:Progestins; D006854:Hydrocortisone
keywords: androgens; immunoassay; mass spectrometry; polycystic ovary syndrome; testosterone