title: Characterization of functionally typical and atypical types of polycystic ovary syndrome.
abstract: BACKGROUND
  The typical polycystic ovary syndrome (PCOS) phenotype includes 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHag) testing. Functionally atypical PCOS lacks this feature.
  
  
  OBJECTIVE
  The hypothesis was tested that the typical PCOS ovarian dysfunction results from intrinsically increased sensitivity to LH/human chorionic gonadotropin (hCG) due to a flaw in FSH action. PARTICIPANTS/DESIGN/INTERVENTIONS/MAIN OUTCOME MEASURES: After phenotyping a cohort of 60 women, steroid and inhibin-B responses to gonadotropins were evaluated in representative typical (n = 7) and atypical (n = 5) PCOS and healthy controls (n = 8). Submaximal hCG testing before and after an FSH test dose was performed in random order before and after prolonged ovarian suppression by depot GnRHag.
  
  
  METHODS
  The study was performed at a Clinical Research Center.
  
  
  RESULTS
  Of our PCOS cohort, 68% were the typical type. Typical PCOS had 17OHP hyperresponsiveness and, unlike controls, significant androgen and estradiol responses to hCG. FSH increased inhibin-B and did not inhibit free testosterone or enhance estradiol responsiveness to hCG, all unlike controls. After ovarian suppression, 17OHP, androstenedione, and inhibin-B responsiveness to gonadotropin testing persisted. Atypical PCOS had significantly higher body mass index but lower ovarian volume and plasma free testosterone than typical PCOS. Steroid responses to hCG were insignificant and similar to controls. FSH suppressed free testosterone but stimulated inhibin-B. The estradiol level after combined hCG-FSH was subnormal. Free testosterone was less GnRHag suppressible than in typical PCOS.
  
  
  CONCLUSIONS
  Typical PCOS is characterized by intrinsic ovarian hypersensitivity to hCG to which excessive paracrine FSH signaling via inhibin-B may contribute. Atypical PCOS is due to a unique type of ovarian dysfunction that is relatively gonadotropin hyposensitive.
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hirshfeld-Cytron
authors.forename: Randall B
authors.initials: RB
authors.lastname: Barnes
authors.forename: David A
authors.initials: DA
authors.lastname: Ehrmann
authors.forename: Anthony
authors.initials: A
authors.lastname: Caruso
authors.forename: Monica M
authors.initials: MM
authors.lastname: Mortensen
authors.forename: Robert L
authors.initials: RL
authors.lastname: Rosenfield
mesh_terms: D000328:Adult; D006063:Chorionic Gonadotropin; D015331:Cohort Studies; D005260:Female; D005640:Follicle Stimulating Hormone; D012739:Gonadal Steroid Hormones / Q000097:blood; D006107:Granulosa Cells / Q000502:physiology; D006801:Humans; D007265:Inhibins / Q000097:blood; D006080:Ovarian Follicle / Q000502:physiology; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*; D013256:Steroids / Q000096:biosynthesis; D013799:Theca Cells / Q000502:physiology; D055815:Young Adult
chemical_list: D006063:Chorionic Gonadotropin; D012739:Gonadal Steroid Hormones; D013256:Steroids; C422364:inhibin B; D007265:Inhibins; D005640:Follicle Stimulating Hormone