Endocrine Abstracts

Objective: Diabetes and obesity cause functional hypogonadism (FH) and impair sperm quality. Testosterone replacement therapy (TRT) improves the signs and symptoms of FH but it further deteriorates sperm quality by inhibiting the endogenous gonadal axis. The effect of glucagon-like peptide-1 receptor agonists (GLP-1-RAs) on FH is suggested to be beneficial due to weight loss. However, the effect of GLP-1 RAs on sperm quality in patients with type 2 diabetes mellitus and obesity has not been sufficiently investigated.

Aim: We compared the effects of semaglutide and TRT on parameters of FH and semen quality in men with type 2 diabetes mellitus and obesity.

Design: We designed a randomized open-label trial that included 26 men with type 2 diabetes (aged 50 [46 to 60] years, BMI 35.9 [32.8 to 38.7] kg/m²) and FH, characterized as the presence of at least 2 symptoms consistent with hypogonadism, two values of total testosterone below 11 nmol/l measured at least four weeks apart and exclusion of other causes of hypogonadism. Participants were randomized to semaglutide 1 mg/week or intramuscular testosterone undecanoate 1000 mg for a period of 24 weeks by following the standard titration protocols.

Methods: We measured anthropometric parameters and parameters of FH. Participants completed questionnaires of the International Index of Erectile Function-15 (IIEF-15) and the Aging Symptoms in Men (AMS). Seminal fluid analysis included measurements of ejaculate volume, sperm count, concentration, morphology and total number of motile sperm. All assessments were performed at baseline and after 24 weeks of treatment.

Results: Both groups experienced a significant increase in total testosterone and an improvement in AMS score, whereas IIEF-15 score was significantly improved only in the TRT group. Seminal fluid volume, total mobile sperm cell concentration, and sperm normal morphology did not significantly change compared to baseline and did not differ between the groups at the end of the study. However, there was a significant difference between the groups in sperm cell concentration (semaglutide 16.7 [-2.6 to 70.5]% vs TRT -60.6 [-80.2 to -13.2]%; P=0.039). Significant weight loss (baseline 115 [102 to 120] kg vs 24-week 99 [96 to 118] kg; P=0.004) and visceral adipose tissue reduction as assessed by dual x-ray absorptiometry were achieved in semaglutide group (P> 0.05 for between-treatment effect).

Conclusion: Semaglutide was superior to TRT in improving body composition and comparably increased testosterone along with improved AMS score. As opposed to TRT, semaglutide maintained sperm quality.