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

Abstract 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.