Ovarian suppression with a gonadotropin-releasing hormone agonist does not alter insulin-stimulated glucose disposal.
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.
Cooper
Brian C
BC
Department of Obstetrics and Gynecology, University of Vermont, Burlington, Vermont 05405, USA.
Sites
Cynthia K
CK
Casson
Peter R
PR
Toth
Michael J
MJ
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
D001786:Blood Glucose; D007328:Insulin; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide