Acute Recapitulation of the Hyperinsulinemia and Hyperlipidemia Characteristic of Metabolic Syndrome Suppresses Gonadotropins

Objective: To determine the effect of lipid/heparin versus saline infusion, with or without concurrent euglycemic hyperinsulinemia, on serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Obesity is associated with hyperlipidemia, insulin resistance, and relative hypogonadotropic hypogonadism. It was hypothesized that acutely elevated fatty acids and insulin would impair gonadotropin secretion. Methods: Regularly cycling women and men without obesity underwent a crossover 6-hour infusion study over four visits. Participants received infusions of saline-control, lipid/heparin, insulin, and lipid/heparin plus insulin. Serum FSH and LH were measured by immunoassay. Results: In women (n=10), infusion of lipid plus insulin significantly reduced LH, from 4.6 IU/L (3.7-5.4) ( mean [95% confidence interval]) to 3.3 IU/L (2.3-4.4); P=0.03, and FSH, from 3.9 IU/L (3.2-4.6) to 3.1 IU/L (2.3-3.8); P=0.03, compared to saline-control. Similarly, in men ( n=10), LH, 3.3 IU/L (2.4-4.1), and FSH, 2.1 IU/L (1.4-2.8), were significantly reduced after the combined infusion (2.2 [1.3-3.1] IU/L and 1.5 [0.8-2.1] IU/L; P=0.03, P=0.02, respectively). Neither lipid nor insulin alone significantly impacted gonadotropin levels compared to saline-control. Conclusions: Hyperinsulinemia combined with elevated lipids acutely suppresses LH and FSH, providing a possible mechanism underlying the relative hypogonadotropic hypogonadism of obesity. Effects of insulin on the hypothalamic-pituitary-gonadal axis may be dependent on the concomitant metabolic environment.