title: Defining Hyperandrogenism in Women With Polycystic Ovary Syndrome: A Challenging Perspective.
abstract: This study was designed to assess the steroid profiling by liquid chromatography coupled with tandem mass spectrometry in PCOS women with different phenotypes.
  
  
  
  Cross-sectional study.
  
  
  
  University hospital of Bologna, Italy.
  
  
  
  A total of 156 PCOS women and 141 controls comparable for age were investigated. All underwent a steroid profiling by liquid chromatography coupled with tandem mass spectrometry. Metabolic parameters were also investigated and hirsutism was measured by the modified Ferriman-Gallwey (mF-G) score.
  
  
  
  Three distinct phenotypes were initially defined according to the combination of hirsutism (mF-G ≥ 8) and/or high testosterone (T) (HA), oligo-amenorrhea (OA), and polycystic ovarian morphology (PCOm); OA + PCOm (n = 43), HA + OA (n = 65), and HA + OA + PCOm (n = 45). T, androstenedione (A), and free androgen index (FAI) levels progressively increased in the 3 PCOS phenotypes with respect to the controls, with the highest values in the HA + OA + PCOm phenotype. The various combinations of hirsutism, high T, high A, and high FAI made it possible to categorize the 3 original phenotypes into 8 hyperandrogenic subgroups, characterized by divergent additional steroid profile and metabolic pattern. A total of 90% of patients with PCOS thus proved hyperandrogenic. Interestingly, half the PCOS women originally classified as having the OA-PCOm phenotype were categorized in a hyperandrogenic subgroup. No significant correlation was found between T, A, and the mF-G score. In contrast, significant correlation was found between A and both T and FAI.
  
  
  
  This study provides evidence that, by including a steroid profile in the definition of hyperandrogenemia, the majority of women with PCOS are hyperandrogenic, although a clinical and biochemical heterogeneity exists. In addition, these data demonstrate that hirsutism and high androgen levels cannot be used indifferently to define hyperandrogenism.
authors.affiliation: Division of Endocrinology (R.P., L.Z., F.F., M.M., A.F., A.M.M.L., A.R., D.R., A.G.), Department of Medical and Surgical Sciences, and Centre for Applied Biomedical Sciences (F.F., M.M., A.F.), University Alma Mater Studiorum, Sant'Orsola-Malpighi Hospital, Bologna, 40138 Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Pasquali
authors.affiliation: Division of Endocrinology (R.P., L.Z., F.F., M.M., A.F., A.M.M.L., A.R., D.R., A.G.), Department of Medical and Surgical Sciences, and Centre for Applied Biomedical Sciences (F.F., M.M., A.F.), University Alma Mater Studiorum, Sant'Orsola-Malpighi Hospital, Bologna, 40138 Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.affiliation: Division of Endocrinology (R.P., L.Z., F.F., M.M., A.F., A.M.M.L., A.R., D.R., A.G.), Department of Medical and Surgical Sciences, and Centre for Applied Biomedical Sciences (F.F., M.M., A.F.), University Alma Mater Studiorum, Sant'Orsola-Malpighi Hospital, Bologna, 40138 Italy.
authors.forename: Flaminia
authors.initials: F
authors.lastname: Fanelli
authors.affiliation: Division of Endocrinology (R.P., L.Z., F.F., M.M., A.F., A.M.M.L., A.R., D.R., A.G.), Department of Medical and Surgical Sciences, and Centre for Applied Biomedical Sciences (F.F., M.M., A.F.), University Alma Mater Studiorum, Sant'Orsola-Malpighi Hospital, Bologna, 40138 Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mezzullo
authors.affiliation: Division of Endocrinology (R.P., L.Z., F.F., M.M., A.F., A.M.M.L., A.R., D.R., A.G.), Department of Medical and Surgical Sciences, and Centre for Applied Biomedical Sciences (F.F., M.M., A.F.), University Alma Mater Studiorum, Sant'Orsola-Malpighi Hospital, Bologna, 40138 Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Fazzini
authors.affiliation: Division of Endocrinology (R.P., L.Z., F.F., M.M., A.F., A.M.M.L., A.R., D.R., A.G.), Department of Medical and Surgical Sciences, and Centre for Applied Biomedical Sciences (F.F., M.M., A.F.), University Alma Mater Studiorum, Sant'Orsola-Malpighi Hospital, Bologna, 40138 Italy.
authors.forename: Antonio Maria
authors.initials: AM
authors.lastname: Morselli Labate
authors.affiliation: Division of Endocrinology (R.P., L.Z., F.F., M.M., A.F., A.M.M.L., A.R., D.R., A.G.), Department of Medical and Surgical Sciences, and Centre for Applied Biomedical Sciences (F.F., M.M., A.F.), University Alma Mater Studiorum, Sant'Orsola-Malpighi Hospital, Bologna, 40138 Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Repaci
authors.affiliation: Division of Endocrinology (R.P., L.Z., F.F., M.M., A.F., A.M.M.L., A.R., D.R., A.G.), Department of Medical and Surgical Sciences, and Centre for Applied Biomedical Sciences (F.F., M.M., A.F.), University Alma Mater Studiorum, Sant'Orsola-Malpighi Hospital, Bologna, 40138 Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Ribichini
authors.affiliation: Division of Endocrinology (R.P., L.Z., F.F., M.M., A.F., A.M.M.L., A.R., D.R., A.G.), Department of Medical and Surgical Sciences, and Centre for Applied Biomedical Sciences (F.F., M.M., A.F.), University Alma Mater Studiorum, Sant'Orsola-Malpighi Hospital, Bologna, 40138 Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gambineri
mesh_terms: D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006628:Hirsutism / Q000097:blood / Q000150:complications*; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000150:complications*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000150:complications*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D000735:Androstenedione; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone