Acute Effects of Glucagon on Reproductive Hormone Secretion in Healthy Men.

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Glucagon increases energy expenditure; consequently, glucagon receptor agonists are in development for the treatment of obesity. Obesity negatively impacts the reproductive axis, and hypogonadism itself can exacerbate weight gain. Therefore, knowledge of the effects of glucagon receptor agonism on reproductive hormones is important for developing therapeutics for obesity; but reports in the literature about the effects of glucagon receptor agonism on the reproductive axis are conflicting.To investigate the effect of glucagon administration on reproductive hormone secretion in healthy young men.Single-blinded, randomized, placebo-controlled crossover study.Clinical Research Facility, Imperial College Healthcare NHS Trust.Eighteen healthy eugonadal men (mean±SEM: age 25.1±1.0years; BMI 22.5±0.4kg/m2; testosterone 21.2±1.2nmol/L).Eight-hour intravenous infusion of 2pmol/kg/min glucagon or rate-matched vehicle infusion.Luteinizing hormone (LH) pulsatility; LH, follicle stimulating hormone (FSH) and testosterone levels.Although glucagon administration induced metabolic effects (insulin AUC: vehicle 1065±292min.µU/mL vs glucagon 2098±358min.µU/mL, p<0.0001), it did not affect LH pulsatility (number of LH pulses/500min: vehicle 4.7±0.4, glucagon 4.2±0.4, p=0.22). Additionally, there were no significant differences in circulating LH, FSH or testosterone levels during glucagon administration compared with vehicle administration.Acute administration of a metabolically active dose of glucagon does not alter reproductive hormone secretion in healthy men. These data are important for the continued development of glucagon-based treatments for obesity.

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