A quarter of men with obesity or type 2 diabetes have hypogonadotropic hypogonadism. Animal studies and in vitro data have shown that insulin action and insulin responsiveness in the brain are necessary for the maintenance of the functional integrity of the hypothalamo-hypophyseal-gonadal axis. We conducted a randomized, placebo-controlled trial to evaluate the effect of one dose of intranasal insulin (40 IU of regular insulin) or saline on LH concentrations in 14 men (8 with type 2 diabetes and 6 healthy lean men). Insulin or saline was administered intranasally on two different occasions, at least one week apart. Blood samples were collected to measure LH concentrations every 15 minutes for 5 hours. Study drug was administered intranasally after a 2-hour baseline sampling period. Patients remained fasting throughout the procedure. The primary endpoint of the study was to compare the change in LH concentrations after intranasal insulin as compared to placebo (intranasal saline). Change was defined as the difference between baseline LH concentrations (average of the 9 samples collected in two hours prior to drug administration) and average LH concentrations following drug administration (average of the 12 samples collected in 3 hours). There was no change in LH concentrations following insulin administration as compared to placebo in men with diabetes or in lean men. We conclude that one dose of 40 IU of regular insulin administered intranasally does not change LH concentrations acutely in men.