title: Hyperinsulinemia amplifies GnRH agonist stimulated ovarian steroid secretion in women with polycystic ovary syndrome.
abstract: BACKGROUND
  In vitro data show that insulin may enhance basal and LH-stimulated ovarian androgen secretion, particularly in theca cells from women with polycystic ovary syndrome (PCOS). However, in vivo studies gave inconsistent results.
  
  
  OBJECTIVE
  The objective of the study was to assess whether hyperinsulinemia affects in vivo ovarian steroid secretion and steroid metabolism.
  
  
  METHODS
  This was a controlled cross-sectional study, conducted in a tertiary care academic center.
  
  
  METHODS
  Nine young PCOS women participated in the study.
  
  
  METHODS
  Participants were submitted, in two separate days, to a GnRH agonist stimulation (buserelin 100 μg, s.c.), during a 17-h hyperinsulinemic (80 mU/m(2) · min) euglycemic clamp and, as a control, during saline infusion. Adrenal steroid secretion was suppressed by dexamethasone.
  
  
  METHODS
  During both protocols, before and after GnRH agonist stimulation, serum insulin, gonadotropins, cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, estradiol, and urinary androgen metabolites were measured.
  
  
  RESULTS
  Insulin increased from 25.1 ± 13.3 to 341.5 ± 102.6 mU/liter during the clamp, whereas it did not significantly change during saline infusion. Baseline steroids and gonadotropins were similar in the two protocols. During hyperinsulinemia, GnRH agonist-stimulated serum progesterone and androstenedione were significantly higher than during saline infusion, and 17-hydroxyprogesterone was of borderline significance. Moreover, 24 h after GnRH agonist stimulation, testosterone was higher after hyperinsulinemia. Serum gonadotropins and estradiol response did not differ between the protocols. Urinary androgen metabolites excretion significantly increased after GnRH agonist stimulation, but the increase was similar during insulin and saline infusions.
  
  
  CONCLUSIONS
  These in vivo data show that sustained hyperinsulinemia potentiates gonadotropin-stimulated ovarian androgen steroidogenesis. Insulin-induced increase in ovarian hormone secretion is not accompanied by an increased steroid metabolism.
authors.affiliation: Division of Endocrinology and Metabolism, University and Azienda Ospedaliera Universitaria Integrata Verona, I-37126 Verona, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Tosi
authors.forename: Carlo
authors.initials: C
authors.lastname: Negri
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Perrone
authors.forename: Romolo
authors.initials: R
authors.lastname: Dorizzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Castello
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
authors.forename: Paolo
authors.initials: P
authors.lastname: Moghetti
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose; D002064:Buserelin / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007328:Insulin / Q000097:blood; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000097:blood*; D011966:Receptors, LHRH / Q000819:agonists*
chemical_list: D001786:Blood Glucose; D005300:Fertility Agents, Female; D012739:Gonadal Steroid Hormones; D007328:Insulin; D011966:Receptors, LHRH; D002064:Buserelin