Effect of ovarian suppression with gonadotropin-releasing hormone agonist on glucose disposal and insulin secretion

Abstract

Several lines of evidence suggest that ovarian hormones influence glucose homeostasis, although their exact role in humans has not been clearly defined. In the present study, we sought to test the hypothesis that ovarian hormones regulate glucose homeostasis by examining the effect of pharmacologically-induced ovarian hormone deficiency on glucose disposal and insulin secretion. Young, healthy women with regular menstrual patterns were studied during the follicular and luteal phases of their cycle at baseline and after two months of treatment with gonadotropin-releasing hormone agonist (GnRHa; n=7) or placebo (n=6). Using hyperglycemic clamps, in combination with stable isotope-labeled (i.e., 13 C and 2 H) glucose tracers, we measured glucose disposal and insulin secretion. Additionally, we assessed body composition and regional fat distribution using radiologic imaging techniques, as well as glucoregulatory hormones. Ovarian hormone suppression with GnRHa did not alter body composition, abdominal fat distribution or thigh tissue composition. There was no effect of ovarian suppression on total, oxidative or non-oxidative glucose disposal expressed relative to plasma insulin level. Similarly, no effect of ovarian hormone deficiency was observed on first-or second phase insulin secretion or insulin clearance. Finally, ovarian hormone deficiency was associated with an increase in circulating adiponectin levels, but no change in leptin concentration. Our findings suggest that a brief period of ovarian hormone deficiency in young, healthy eugonadal women does not alter glucose disposal index or insulin secretion, supporting the conclusion that ovarian hormones play a minimal role in regulating glucose homeostasis. Our data do, however, support a role for ovarian hormones in the regulation of plasma adiponectin levels.

Serum IGF1 and insulin levels in girls with normal and precocious puberty

“…In contrast, insulin levels and adiposity increased significantly from the pretreatment visit to the 1-year evaluation without significant changes observed at the 3-month visit. Accordingly, short-term gonadal suppression in young adult women is not associated with changes in glucose homeostasis (31). Surprisingly, the persistent gonadal suppression and concomitant regression of sexual characteristics induced by the GNRHa treatment neither reversed IGF1 nor insulin to prepubertal levels.…”

Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes

“…Plasma [6,6-2H2]glucose enrichment was measured by gas chromatography-mass spectrometry in the electron impact mode (Agilent 5973; Agilent Technologies, Palo Alto, CA), as described previously [42]. Prior to measurement, glucose was derivatized to the butylboronate acetate derivative.…”

Relationship of androgens to body composition, energy and substrate metabolism and aerobic capacity in healthy, young women

“…We recruited healthy, non-obese, glucose tolerant, cycling females with no history or clinical evidence of endocrine pathology for studies evaluating the effect of ovarian steroid hormones on metabolic function [2–5]. These criteria were chosen to avoid the confounding affects of obesity, insulin resistance, and hyperandrogenemia.…”