Men treated with GLP-1 receptor agonists had significant increases in testosterone levels, according to findings from a retrospective analysis.
Among men who received semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound), median total testosterone increased from 320 to 419 ng/dL and median free testosterone increased from 9.0 to 10.4 ng/dL (P<0.001 for both), reported Andrés Heriberto Guillén-Lozoya, MD, of the Mayo Clinic in Rochester, Minnesota, at the American Urological Association annual meeting.
After adjusting for age and body mass index (BMI), total testosterone increased by a median of 97.6 ng/dL, while free testosterone increased by 1.3 ng/dL (P<0.001 for both).
Meanwhile, median BMI decreased from 33.6 to 30.4 (P<0.001).
At baseline, patients with lower BMI tended to have higher testosterone levels overall, Guillén-Lozoya observed.
However, "one of the most interesting findings from our study was that changes in testosterone were not directly correlated with BMI reduction alone," he noted. "What this suggests is that the hormonal improvement observed may not be explained solely by weight loss."
Guillén-Lozoya said his team's leading hypothesis is "testosterone improvement is slightly multifactorial."
"Weight reduction and reduced adiposity probably contributed significantly, but additional mechanisms may also be involved, such as improved insulin sensitivity, reduced inflammation, reduced aromatization for the adipose tissue, and potentially a restoration or improvement of the hypothalamic-pituitary-gonadal axis," he explained.
While the effects of GLP-1 receptor agonists on glycemic control and weight reduction have been well established, "much less is known about their impact in men's health," Guillén-Lozoya said, in explaining the rationale behind the study. "This is particularly important because obesity, insulin resistance, and metabolic syndrome are strongly associated with functional hypogonadism and reduced testosterone levels in men."
"GLP-1 receptor agonists may have favorable effects in these male patients, particularly in obese and metabolically complicated men," he added. "As the use of these medications continues to expand worldwide, understanding their broader implications in men's health will become increasingly important."
The use of GLP-1 receptor agonists could eventually emerge as an adjunctive strategy for men with functional hypogonadism related to obesity and metabolic disease, Guillén-Lozoya said. "However, I will not frame them as primary or as a replacement for standard hypogonadism management, but rather they may function as an aid or as a disease-modifying metabolic therapy ... in selected patients."
In this cross-sectional study of electronic health record data, Guillén-Lozoya and colleagues retrospectively analyzed men who received semaglutide or tirzepatide and had pre- and post-treatment testosterone measurements from October 2018 to October 2025 at the Mayo Clinic. Paired total testosterone and free testosterone data were available for 1,629 and 1,216 men, respectively.
Co-author Tobias Kohler, MD, also of the Mayo Clinic, pointed out that the study included men who were given a prescription for one of the two drugs, but the data did not indicate how many men continued to take them.
The discontinuation rate in non-clinical trials is about 40% for these drugs, and 10% to 20% in clinical trials, he said. "So, this increase in testosterone is actually probably underestimated."
Guillén-Lozoya acknowledged that the study had several limitations, including the fact that it was a retrospective study, that testosterone measurements were not standardized by timing, and that causality cannot be established. Residual confounding also remains plausible.
Disclosures
Guillén-Lozoya had no disclosures.
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