Most data on GLP-1 RAs and male fertility come from animal trials or small studies investigating weight loss, but experts say there might be potential here.
and tirzepatide, has raised questions about what therapeutic effects this class of medication might have beyond their current indications for type 2 diabetes andExperts say the connection between GLP-1 RAs and improved male fertility makes sense biologically. For starters, overweight and obesity are strongly associated within several overlapping ways.
Obesity is also linked to lower levels of inhibin B, which stimulates testosterone secretion in Sertoli cells, which, when combined with the proinflammatory state of obesity, "results in a less favorable environment for sperm production," he said. Finally, the link between obesity and poorer sexual function further inhibits fertility potential, he added.
One of the key questions requiring further research, then, is whether GLP-1 agents have direct effects on male fertility independent of a reduction in obesity. The randomized controlled trials comparing liraglutide and lifestyle modifications failed to find additional effects on semen in the men taking liraglutide; however, the study had only 56 participants, and results from liraglutide cannot be generalized to potential effects of semaglutide or tirzepatide. Sadeghi-Nejad said.
"We know that there are GLP-1 receptors in the reproductive tract, but the extent of the downstream effect of stimulating those receptors, I don't think we know well," said John P. Lindsey II, MD, MEng, an assistant professor of urology at University of California San Francisco Health.
Sadeghi-Nejad said that he and his co-authors are working on developing a registry for men who take GLP-1 RAs that would enable long-term tracking of multiple andrologic outcomes, including fertility and sexual dysfunction. Such a registry could theoretically be useful in tracking pregnancy and offspring outcomes as well.. But these have their drawbacks, Sadeghi-Nejad pointed out; in the overweight population in particular, they "are not necessarily ideal," he said.
"Despite the established popularity of GLP-1 receptor agonists, there may be some reluctance among urologists and fertility specialists to prescribe them, with some others advocating for their use to enhance semen parameters," Ramasamy said. "However, robust scientific evidence is still lacking, necessitating caution and a wait for more substantial data."
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