CHICAGO — Current evidence does not show a negative long-term effect of GLP-1 agonists on male fertility, and some data suggest the drugs may offer benefits, the results of a systematic review found.

“One thing we proved is that they do not harm the reproductive axis in men. There was no inhibitory effect, so we can counsel our patients that the drugs don’t impact the reproductive system negatively,” study author Pratibha Natesh, MBBS, Warwick Medical School, Coventry, England, told Medscape Medical News.

Still, the data in this area are sparse, she noted. “We only found three randomized controlled trials that evaluated the impact of the GLP-1 analog on the reproductive system with prolonged use. … But the results were quite encouraging.”

Natesh presented the data in a poster at ENDO 2026: The Endocrine Society Annual Meeting.

A systematic search of PubMed and the Cochrane Library identified five randomized clinical trials that met the inclusion criteria of involving men aged 18-65 years receiving a GLP-1 agonist with appropriate comparators. However, only three trials provided data suitable for quantitative analysis.

In one randomized, double-blind, placebo-controlled crossover study, 4 weeks of treatment with dulaglutide in healthy men reduced A1c and showed no significant effect on reproductive hormones, sexual function scores, or semen parameters. The findings support “biological activity without [hypothalamic-pituitary-gonadal] axis suppression,” Natesh and colleagues said in their poster.

In a 16-week prospective randomized open-label study of men with obesity and functional hypogonadism, those randomly assigned to liraglutide had increased total testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as metabolic improvements compared with men randomized to transdermal testosterone.

In a 24-week randomized open-label trial of men with obesity, type 2 diabetes, and functional hypogonadism randomly assigned to semaglutide or intramuscular testosterone, improvements were seen with semaglutide in sperm morphology, total testosterone levels, and symptoms of hypogonadism, with preservation of testosterone and gonadotropins.

“Overall, available randomized clinical trial evidence does not show consistent HPG [hypothalamic-pituitary-gonadal]-axis suppression in men with obesity or metabolic dysfunction. Reproductive improvements are likely mediated through weight loss and improved metabolic health,” Natesh and colleagues said.

Because the evidence is limited and heterogeneous, larger randomized controlled trials that specifically assess reproductive outcomes in men taking GLP-1s are needed, they added.

Questions Remain

Asked to comment, Bradley Anawalt, MD, professor and vice-chair of medicine at the University of Washington, Seattle, told Medscape Medical News that the findings “take away the notion that maybe these drugs could have some direct effect on suppressing the hormones.” He pointed out, however, that the use of active comparators in two of the trials could affect the findings.

Regarding the possibility of a beneficial effect on fertility, Anawalt noted that “surprise pregnancies in women occur because these drugs are helping restore their reproductive function. That probably happens in men, but we don’t have really good long-term studies to answer that question.”

Anawalt added that the improvement in fertility resulting from weight loss probably wouldn’t occur during active weight loss.

“Obesity tends to suppress reproductive function in both males and females. But if you’re starving, that also suppresses your reproductive function. The weight needs to stabilize on these drugs before reproductive function comes back to normal. If you go from obese to starving, you’re still going to be having a suppressed function,” Anawalt explained.

And as for the mechanism, he said, “We think it’s the loss of weight and restoring this balance where the body doesn’t feel like it’s starving, but there are these important health benefits on stroke, heart attacks, and kidney disease that are independent of weight loss. So, it leaves the question open that maybe there’s an independent effect on fertility too. … I think the best and still simple explanation is that these drugs have effects on the brain directly that may be affecting all these other things as well.”

Natesh and Anawalt reported no disclosures.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social.