Semaglutide Improves Sperm Quality and Testosterone Levels in Obese Men with Type 2 Diabetes and Hypogonadism: Study

The research, which focused on men with both obesity and type 2 diabetes, found that semaglutide significantly improved sperm morphology, testosterone levels, and symptoms of hypogonadism. The findings open the door to new treatment options for men with fertility concerns linked to metabolic and hormonal conditions.

Functional hypogonadism, characterized by low testosterone levels and associated symptoms like fatigue, reduced libido, and erectile dysfunction, is common among men with obesity and type 2 diabetes. The condition can also impair fertility, contributing to difficulties in conceiving. Traditionally, treatment options for functional hypogonadism have included testosterone replacement therapy, but this approach can carry risks, including suppression of sperm production. As a result, many men seeking to improve fertility have limited therapeutic options.

Against the above background, Mojca Jensterle, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia, and colleagues aimed to compare the effects of semaglutide and testosterone replacement therapy (TRT) on semen quality and functional hypogonadism symptoms in men with type 2 diabetes and obesity.

For this purpose, the researchers designed a randomized open-label trial involving 25 men with type 2 diabetes (aged 50 [46–60] years, BMI 35.9 [32.8–38.7] kg/m²) and functional hypogonadism (FH). The participants were randomly assigned to receive either semaglutide (SEMA) 1 mg per week or intramuscular testosterone undecanoate (TRT) 1000 mg every 10–12 weeks for 24 weeks.

Semen analysis and FH parameters were assessed at baseline and after the 24-week treatment period. Additionally, participants completed the International Index of Erectile Function-15 (IIEF-15) and Aging Symptoms in Men (AMS) questionnaires to evaluate erectile function and symptoms of aging.

The following were the key findings of the study:

• Baseline sperm quality in the study cohort was poor, with parameters falling below the 5th percentile of reference values.
• In the SEMA group, there was a significant improvement in morphologically normal sperm from baseline to the end of the study (2% versus 4%).
• In contrast, the TRT group saw a significant decrease in sperm concentration and total sperm count.
• Compared to TRT, the SEMA group had significantly higher levels of morphologically normal sperm, sperm concentration, and total sperm count.
• Both treatment groups experienced an increase in total testosterone levels and an improvement in AMS scores (indicating better aging-related symptoms).
• The IIEF-15 score (which measures erectile function) improved significantly only in the TRT group.

The findings revealed positive effects of semaglutide on body weight, metabolism, general symptoms of functional hypogonadism, and sperm morphology. However, testosterone replacement therapy had a stronger impact on sexual function in men with diabetes and obesity-related FH.

"Given its benefits for reproductive health, semaglutide could be a promising treatment for men with obesity and diabetes-related FH who are seeking to improve fertility. Combining both treatments may offer broader health benefits for certain patients with obesity and diabetes-related FH, warranting further research on this potential approach," the researchers concluded.

Reference:

DOI: https://doi.org/10.1111/dom.16042