Effects of Glucagon-like Peptide-1 on the Reproductive Axis in Healthy Men

• Published in: The journal of clinical endocrinology and metabolism 2020-04, Vol.105 (4), p.1119-1125
• Main Authors: Izzi-Engbeaya, Chioma, Jones, Sophie, Crustna, Yoshibye, Machenahalli, Pratibha C, Papadopoulou, Deborah, Modi, Manish, Panayi, Christos, Starikova, Jessica, Eng, Pei Chia, Phylactou, Maria, Mills, Edouard, Yang, Lisa, Ratnasabapathy, Risheka, Sykes, Mark, Plumptre, Isabella, Coumbe, Ben, Wing, Victoria C, Pacuszka, Ewa, Bech, Paul, Minnion, James, Tharakan, George, Tan, Tricia, Veldhuis, Johannes, Abbara, Ali, Comninos, Alexander N, Dhillo, Waljit S
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers - analysis; Clinical s; Cross-Over Studies; Diabetes mellitus (non-insulin dependent); Follicle-stimulating hormone; Follow-Up Studies; Food intake; GLP-1 receptor agonists; Glucagon; Glucagon - metabolism; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - pharmacology; Health aspects; Hormone therapy; Human reproduction; Humans; Incretins - pharmacology; Insulin; Insulin secretion; Insulin Secretion - drug effects; Intravenous administration; Luteinizing hormone; Male; Men; Peptide hormones; Peptides; Physiological aspects; Prognosis; Reproduction - drug effects; Reproductive system; Secretion; Single-Blind Method; Testing; Testosterone; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa072

Abstract Context Glucagon-like peptide-1 (GLP-1) potently reduces food intake and augments glucose-stimulated insulin secretion. Recent animal data suggest that GLP-1 may also influence reproduction. As GLP-1 receptor agonists are currently widely used in clinical practice to treat obesity/type 2 diabetes, it is necessary to determine the effects of GLP-1 on the reproductive system in humans. Objective To investigate the effects of GLP-1 administration on the reproductive axis in humans. Design Single-blind, randomized, placebo-controlled crossover study. Setting Clinical Research Facility, Imperial College Healthcare NHS Trust. Participants Eighteen healthy men (mean age 24.7 ± 0.1years, mean BMI 22.1 ± 0.4kg/m2). Intervention Eight-hour intravenous infusion of 0.8 pmol/kg/min GLP-1 or rate-matched vehicle infusion. Main Outcome Measures Number of luteinizing hormone (LH) pulses, LH, follicle-stimulating hormone (FSH), and testosterone levels. Results The number of LH pulses (number of LH pulses/500 min: vehicle 4.2 ± 0.4, GLP-1 4.5 ± 0.3, P = 0.46), LH area under the curve (AUC) (vehicle 1518 ± 88min.IU/L, GLP-1 1524 ± 101min.IU/L, P = 0.95), follicle-stimulating hormone AUC (vehicle 1210 ± 112 min IU/L, GLP-1 1216 ± 112 min IU/L, P = 0.86), and testosterone AUC (vehicle 10893 ± 615 min nmol/L, GLP-1 11088 ± 792 min nmol/L, P = 0.77) did not significantly differ during vehicle and GLP-1 administration. Glucagon-like peptide-1 significantly reduced food intake (vehicle 15.7 ± 1.3 kcal/kg, GLP-1 13.4 ± 1.3 kcal/kg, P = 0.01). Conclusions In contrast to the animal literature, our data demonstrate that acute GLP-1 administration does not affect reproductive hormone secretion in healthy men.