AUA 2025: GLP-1 RAs could improve sperm count in overweight men

Skyler Howell, MD
Credit: X.com

GLP-1 receptor agonists (GLP-1 RAs) could provide more than weightless benefits, according to a new study presented at the American Urological Association's (AUA) 2025 Annual Meeting.

An analysis of nearly 4000 men with overweight or obesity, results of the retrospective study suggest use of GLP-1 RAs was associated with greater improvements in sperm count relative to nonuse among the matched cohort.

“Because obesity can lead to poor fertility, we wonder whether these drugs might have a therapeutic role,” explained lead investigator Skyler Howell, MD, a fourth-year urology resident at the University of Texas in Houston. “In fact, this has been demonstrated in obesity related female factor in fertility, but the data in men is less clear. Some nonrandomized studies exist suggesting these drugs are at best associated with improvements in sperm count and at worst do not negatively affect semen.”

Few classes of medication have captivated the medical community and public consciousness in the same manner as GLP-1 RAs in the last decade. Initially approved for type 2 diabetes, the class, led primarily by semaglutide, grew to be among the most prescribed classes of medications because of revelations surrounding weight loss benefits as well as cardiovascular and renal protective effects. Though these previous benefits have garnered semaglutide expanded indications with the US FDA, additional studies purport further downstream benefits with use. Among the benefits observed in retrospective studies is a potential effect on fertility among female patients with overweight or obesity.^1,2

Howell and colleagues designed the AUA 2025 study to further explore this effect and whether it might be observed in male patients. To do so, investigators designed their study as a retrospective cohort study using the TriNetX research network evaluated whether GLP-1 RA exposure was associated with improvements in semen analysis parameters among overweight or obese men with abnormal sperm count, motility, or semen volume, based on World Health Organization 6th edition criteria.¹

The analysis controlled for confounders, including diabetes mellitus and body mass index (BMI), through propensity score matching for age, race, BMI, history of diabetes, hypertension, tobacco use, and alcohol-related disorders. Patients with a history of normal semen parameters prior to an abnormal result were excluded from the relevant analyses.¹

A total of 417 GLP-1 RA-exposed patients were matched with 3182 controls. Before matching, GLP-1 RA-exposed individuals were older and had greater rates of diabetes, hypertension, and a greater mean BMI. After matching, the cohorts included 385 patients each. Investigators pointed out there were no significant demographic differences between the groups except for a greater mean BMI in the study group (41.0 vs 38.7; P <.001).¹

Upon analysis, investigators found improvements in sperm count were observed in 10 of 351 GLP-1 RA-exposed patients compared to none among 358 controls (Absolute Risk, +2.8%; P = .001). Further analysis revealed there were no significant differences seen in motility improvements (AR, -0.4%; P = .805) and improvements in semen volume were more frequent among controls than among GLP-1 RA-exposed patients (AR, -4.6%; P = .001).¹

“In a group with about 3600 patients, we found 3 things. First and foremost, about 3% of the study group developed normal sperm counts, which was entirely attributable to GLP-1 exposure given. None of the control group did. We also see that these changes happen relatively quickly… Second, some men experienced normalized motility, but this effect was not attributable to GLP one exposure as the control groups also had a similarity of normalizing,” Howell explained. “Finally, there was no volume normalization in the study group, even though some of the control group normalized. This may suggest an inhibitory effect of these medications, possibly via hormonal action, given the relationship between low testosterone and semen volume.”

References:

1. Howell SM, Sabogal CR, Saffati G, et al. PD23-06 GLP1-AGONIST USE IS ASSOCIATED WITH IMPROVED SPERM COUNTS IN OVERWEIGHT AND OBESE MEN. J Urol. 2025;213(5S):e826. doi:10.1097/01.JU.0001110004.96669.db.06

2. Duah J, Seifer DB. Medical therapy to treat obesity and optimize fertility in women of reproductive age: a narrative review. Reprod Biol Endocrinol. 2025;23(1):2. Published 2025 Jan 6. doi:10.1186/s12958-024-01339-y