The effect of estrogen level on glucose-induced changes in serum insulin-like growth factor binding protein-1 concentration

Abstract

Objective: To investigate the regulation of insulin-like growth factor binding protein-1 (IGFBP-1) concentration during ovarian stimulation.

Design: A prospective study of patients undergoing in vitro fertilization treatment.

Setting: Infertility unit at the University Central Hospital of Oulu, a tertiary referral center.

Patients: Sixteen healthy, regularly menstruating lean tubal infertility patients.

Interventions: Oral glucose tolerance test was performed first in a hypoestrogenic state after suppression by long-term gonadotropin-releasing hormone (GnRH) agonist and, second, in a hyperestrogenic state after stimulation by human menopausal gonadotropins.

Main outcome measures: Serum concentrations of IGFBP-1, insulin-like growth factor I (IGF-I), insulin and sex hormone-binding globulin were measured before and 2 hours after glucose administration.

Results: Before and after glucose administration, the serum IGFBP-1 concentrations were significantly higher in the hyperestrogenic state (estradiol [E2] level 3.5 +/- 0.57 nmol/L) after ovarian stimulation than in the GnRH-analogue-induced hypoestrogenic state before the gonadotropin treatment (E2 level 0.10 +/- 0.02 nmol/L). On both occasions glucose-induced hyperinsulinemia caused a significant decrease in the circulating IGFBP-1 levels, whereas the IGF-I levels remained unchanged. There was a significant correlation between E2 and the insulin-suppressed IGFBP-1 level. The sum of follicular diameters correlated positively with the serum IGFBP-1 concentration.

Conclusions: Gonadotropin-induced hyperestrogenism is related to elevated serum IGFBP-1 levels, either via estrogen-stimulated synthesis or via increased contribution from multiple follicles. Glucose-induced hyperinsulinemia suppresses serum IBFBP-1 concentration equally both in the hypoestrogenic and hyperestrogenic states. Because of similar IGF-I levels, it is likely that the biological activity of IGF-I is different before and after gonadotropin stimulations.