Effects of glucagon-like peptide 1 receptor agonists on testicular dysfunction: A systematic review and meta-analysis

Background: Hypogonadism and infertility are two conditions that are heavily affected by overweight and obesity in the male patient. Glucagon-like peptide 1 agonists (GLP-1RAs) are a recently introduced class of antidiabetic drugs with powerful weight-loss effect; this may induce an indirect positive effect on the testicular function. Nevertheless, recent evidence also suggests a potential direct influence of these molecules on the gonadal function. Objectives: Our study aims at evaluating the effects of GLP-1RAs on hormone secretion in male patients and comparing their impact on the testicular function with other antidiabetic agents or weight-lowering drugs. Materials and methods: A literature search was conducted using PubMed, EMBASE, and Scopus database to assess the effects of GLP-1RAs on hormone levels, sperm parameters, and erectile function in overweight and obese men. Before–after analysis and comparison between therapy with GLP-1RAs and other treatment regimens were performed. Results: Seven studies (n = 680) were included in the quantitative analysis. Treatment with GLP-1RAs produced a significant increase in total serum testosterone (TT), with a standardized mean difference of 1.39 ng/mL (95% confidence interval: 0.70, 2.09; p < 0.0001). Free serum testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) showed similar increase, while weight, body mass index (BMI), waist circumference (WC), and glycated hemoglobin (HbA1c) decreased. Meta-regression showed a significant negative correlation between standardized mean difference in TT levels before–after treatment and percentage change in weight and BMI. When compared with other treatment options, GLP-1RAs showed a comparable effect on serum androgens, but greater BMI reduction and increase in serum gonadotropins and indexes of the erectile function. Conclusion: Our systematic review and meta-analysis suggest a possible role for GLP-1RAs in the therapy of functional hypogonadism related to overweight and obesity, while also promoting weight loss. The limitations of the current literature do not allow to demonstrate a direct action of GLP-1RAs on the testicular function.