Effect of GLP1 Agonists on Reproduction

Abstract Obesity, in animals and humans, is associated with male and female reproductive dysfunction. Elucidating the mechanisms by which excessive weight affects reproduction and proving that weight loss improves reproductive function has been difficult. Data in animals and humans demonstrate improvements in reproductive function after weight loss, achieved with or without glucagon-like peptide 1 (GLP1) agonists. In preclinical studies there is evidence that GLP1 agonists have direct effects on the hypothalamus to stimulate luteinizing hormone (LH) secretion and direct beneficial effects on the gonads and the endometrium. Whether GLP-1 agonists provide an added direct beneficial effect on reproductive organs in humans, beyond the benefits mediated by weight loss, remains unclear. However, consideration of GLP1 agonists for the treatment for obesity-associated reproductive dysfunction requires caution, as any weight loss during pregnancy is associated with adverse fetal outcomes, and preclinical studies indicate fetal toxicity of the GLP1 agonist class. Here, we review the available preclinical and clinical evidence of the effects of GLP-1 agonists on human reproductive health, suggest a therapeutic strategy, and list the needs for future research.