title: Ovarian suppression with a gonadotropin-releasing hormone agonist does not alter insulin-stimulated glucose disposal.
abstract: OBJECTIVE
  Aging is associated with reduced tissue sensitivity to insulin. In women, these age-related changes may be accelerated by menopause. The effect of ovarian hormone deficiency on tissue insulin sensitivity in humans, however, has not been defined clearly. Thus, the goal of this study was to evaluate the effect of suppression of endogenous ovarian hormone production on insulin-stimulated glucose disposal.
  
  
  METHODS
  Randomized, single-blind, placebo-controlled trial.
  
  
  METHODS
  General clinical research center.
  
  
  METHODS
  Thirteen healthy, nonobese premenopausal women.
  
  
  METHODS
  Insulin-stimulated glucose disposal was determined by hyperinsulinemic (40 mU/m(2)/min) clamp during the early to midfollicular and midluteal phase of the menstrual cycle. Volunteers then received 2 months of treatment with the GnRH agonist (GnRHa) leuprolide acetate (n = 6) or placebo (n = 7) and were retested.
  
  
  METHODS
  Total, oxidative, and nonoxidative insulin-stimulated glucose disposal.
  
  
  RESULTS
  Because no effect of cycle phase was found on total, oxidative, or nonoxidative glucose disposal, pretreatment follicular and luteal phase values were averaged. Treatment with GnRHa had no effect on total glucose disposal (GnRHa: 10.6 +/- 0.9 to 10.8 +/- 0.9 vs. placebo: 10.2 +/- 0.7 to 10.4 +/- 1.0 mg/kg fat-free mass/min, P = .99). Similarly, there was no effect of GnRHa administration on oxidative (GnRHa: 2.77 +/- 0.58 to 3.89 +/- 0.58 vs. placebo: 2.74 +/- 0.42 to 3.33 +/- 0.62 mg/kg fat-free mass/min, P = .52; n = 6 and 6, respectively) or nonoxidative (GnRHa: 7.82 +/- 0.68 to 6.91 +/- 0.66 vs. placebo: 7.94 +/- 0.72 to 7.79 +/- 0.99 mg/kg fat-free mass/min, P = .59; n = 6 and 6, respectively) components of glucose disposal.
  
  
  CONCLUSIONS
  Our results suggest that endogenous ovarian hormones do not regulate tissue responsiveness to insulin or intracellular pathways of glucose disposal.
authors.affiliation: Department of Obstetrics and Gynecology, University of Vermont, Burlington, Vermont 05405, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Cooper
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Sites
authors.forename: Peter R
authors.initials: PR
authors.lastname: Casson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Toth
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D016729:Leuprolide / Q000494:pharmacology; D008597:Menstrual Cycle / Q000097:blood / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D016037:Single-Blind Method
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide