Do GLP-1 receptor agonists affect sperm quality or male fertility outcomes?

GLP-1 receptors have been identified in key testicular cells, including Sertoli and Leydig cells, as well as in sperm cells themselves. This indicates that GLP-1 signalling may play a direct role in testicular function and sperm biology. Experimental studies suggest that GLP-1 is involved in regulating metabolic processes within the testes, including glucose homeostasis and energy metabolism, which are essential for normal spermatogenesis. In vitro findings also show that GLP-1 can influence Sertoli cell mitochondrial function and glucose utilisation, with low concentrations improving metabolic efficiency, while higher concentrations may induce mitochondrial stress.

Evidence from animal studies further supports a potential beneficial effect of GLP-1 receptor agonists on sperm quality. In obese rodent models, administration of GLP-1 RAs such as exenatide was associated with improvements in sperm motility and DNA integrity, along with reduced testicular inflammation and lower expression of pro-inflammatory cytokines. These findings suggest that GLP-1 RAs may improve sperm quality indirectly by reducing obesity-related metabolic and inflammatory damage within the testes.

Clinical data in humans, however, indicate that improvements in sperm parameters are more closely linked to weight loss rather than a direct drug-specific effect. Studies show that reductions in BMI are associated with increased sperm concentration and total sperm count, as well as improvements in sperm morphology and DNA fragmentation. In a randomized controlled study, men receiving liraglutide did not demonstrate additional improvements in semen parameters beyond those achieved through an initial low-calorie diet, although weight loss itself was associated with improved sperm quality and these benefits were maintained in those who sustained significant weight reduction.

Overall, current evidence suggests that GLP-1 receptor agonists do not negatively affect sperm quality and may contribute to improved reproductive outcomes primarily through weight loss and metabolic improvement. While experimental data indicate possible direct roles in testicular and sperm cell function, these mechanisms have not yet translated into clear, independent clinical effects in humans. Further research is needed to clarify whether GLP-1 RAs have direct fertility-enhancing properties beyond their effects on body weight.

Varnum AA, Pozzi E, Deebel NA, Evans A, Eid N, Sadeghi-Nejad H, Ramasamy R. Impact of GLP-1 Agonists on Male Reproductive Health-A Narrative Review. Medicina (Kaunas). 2023 Dec 27;60(1):50. doi: 10.3390/medicina60010050. PMID: 38256311; PMCID: PMC10820247.

Do GLP-1 receptor agonists affect testosterone levels?

Current evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) do affect testosterone levels, with most data indicating a modest but meaningful improvement in androgen status, particularly in the context of metabolic disease and obesity-related hypogonadism.

A recent systematic review and meta-analysis by Orra et al. (2025) found that treatment with GLP-1 RAs is associated with a significant increase in bioavailable testosterone, alongside a reduction in HbA1c, suggesting both metabolic and endocrine benefits. Bioavailable testosterone, which reflects the fraction of testosterone that is biologically active and readily available to tissues, appears to improve with GLP-1 RA therapy, supporting a potential restoration of androgen function in men with insulin resistance and obesity. This aligns with the well-established relationship between metabolic dysfunction, obesity, and reduced testosterone levels.

In contrast, the same analysis found no statistically significant change in free testosterone or sex hormone-binding globulin (SHBG) levels. This indicates that the effects of GLP-1 RAs on testosterone are not uniform across all hormone fractions, and that the improvement is primarily seen in the biologically active, protein-bound component rather than in circulating free hormone levels.

Individual studies included in the meta-analysis, such as randomized trials of liraglutide, also reported modest increases in total testosterone, particularly in obese men with type 2 diabetes, alongside improvements in weight and insulin sensitivity. However, these changes were variable and appeared to depend on factors such as baseline metabolic status, degree of weight loss, and duration of therapy. Differences between agents may also play a role, as shorter-acting drugs like exenatide showed less consistent effects compared with longer-acting GLP-1 RAs.

Overall, current evidence suggests that GLP-1 receptor agonists are associated with improvements in testosterone levels, particularly bioavailable testosterone, likely mediated through improvements in metabolic health and weight reduction rather than a direct endocrine action. However, because findings vary across studies and heterogeneity is high, further large and well-controlled trials are needed to clarify the extent and clinical significance of these hormonal changes.

Orra SH, Martinez JVN, Porto BC, Passerotti CC, Sardenberg RAS, Da Cruz JAS. Effect of GLP-1 agonists on testosterone levels: a systematic review and meta-analysis. BMC Urol. 2025 Nov 25;25(1):311. doi: 10.1186/s12894-025-02005-0. PMID: 41291666; PMCID: PMC12752444.

What are the most commonly prescribed GLP-1 medications, and how might they influence reproductive health in men?

The most commonly prescribed GLP-1 receptor agonists include liraglutide, semaglutide, exenatide, dulaglutide, and tirzepatide. These medications are primarily used for the management of type 2 diabetes and obesity, where they promote weight loss, improve glycaemic control, and enhance overall metabolic health.

Current evidence suggests that GLP-1 receptor agonists may influence male reproductive health both directly and indirectly. GLP-1 receptors have been identified in Sertoli cells, Leydig cells, and sperm cells, indicating a potential role in testicular function and spermatogenesis (Varnum et al., 2023). Experimental studies have demonstrated improvements in sperm motility, DNA integrity, and testicular inflammation following GLP-1 receptor agonist treatment; however, these findings are largely derived from animal models and have not yet translated into clear, independent clinical effects in humans (Varnum et al., 2023).

In clinical studies, GLP-1 receptor agonists have been associated with improvements in testosterone levels, particularly bioavailable testosterone, as well as improvements in semen parameters such as sperm concentration and total sperm count. However, the available evidence suggests that these reproductive benefits are primarily driven by weight loss and improvements in metabolic health rather than a direct pharmacological effect of the medications themselves (Orra et al., 2025; Andersen et al., 2022). Importantly, there is currently no evidence that GLP-1 receptor agonists negatively affect sperm quality or male fertility.

Despite these promising findings, there remains a lack of research examining the effects of paternal GLP-1 use on conception rates, pregnancy outcomes, live births, or offspring health. Therefore, while GLP-1 receptor agonists may improve several markers associated with male reproductive health, further research is needed to determine their impact on clinically meaningful fertility outcomes.

Andersen, E., Juhl, C.R., Bonde, J.P. and Jensen, T.K. (2022). Weight loss and male reproductive function: a randomized controlled trial investigating semen quality following weight reduction in men with obesity. Human Reproduction, 37(1), pp.29–38.

Orra, S.H., Martinez, J.V.N., Porto, B.C., Passerotti, C.C., Sardenberg, R.A.S. and Da Cruz, J.A.S. (2025). Effect of GLP-1 agonists on testosterone levels: a systematic review and meta-analysis. BMC Urology, 25(1), 311.

Varnum, A.A., Pozzi, E., Deebel, N.A., Evans, A., Eid, N., Sadeghi-Nejad, H. and Ramasamy, R. (2023). Impact of GLP-1 Agonists on Male Reproductive Health: A Narrative Review. Medicina (Kaunas), 60(1), 50.

What does the latest evidence say about the impact of GLP-1 drugs on fertility, pregnancy outcomes?

The latest evidence on GLP-1 receptor agonists and reproductive outcomes remains limited. While emerging studies suggest that GLP-1 drugs may improve some markers of male reproductive health, such as testosterone levels and semen parameters in men with obesity or metabolic dysfunction, the evidence is still preliminary and based on relatively small studies. Systematic reviews have highlighted the need for larger prospective studies to confirm these findings.

Importantly, there are currently no studies that directly evaluate whether paternal use of GLP-1 drugs affects fertility outcomes resulting in pregnancy, live births, or offspring health. Therefore, there is insufficient evidence to determine the impact of male GLP-1 exposure on pregnancy outcomes. Further research is needed to assess the effects of GLP-1 use in men on conception, pregnancy outcomes, and live birth rates.

Are there any risks, side effects, or limitations associated with using GLP-1 medications in men who are trying to conceive?

The use of GLP-1 receptor agonists in men who are trying to conceive is an area where the evidence base remains limited. Current research has not identified specific reproductive risks associated with paternal exposure to GLP-1 medications; however, there is a lack of studies directly examining their effects on male fertility, conception rates, pregnancy outcomes, or live birth outcomes. As a result, the safety profile of GLP-1 receptor agonists in men attempting to conceive has not been fully established, and further research is needed to address these knowledge gaps.

Although most studies have focused on surrogate markers of male fertility rather than pregnancy or live birth outcomes, current evidence suggests that GLP-1 receptor agonists do not negatively affect sperm quality and may be associated with improvements in semen parameters. Improvements in sperm concentration, total sperm count, morphology, and DNA fragmentation have been observed following weight loss in men with obesity, including those using GLP-1 therapies. However, the available evidence indicates that these benefits are likely driven by weight loss and improved metabolic health rather than a direct drug-specific effect (Andersen et al., 2022; Varnum et al., 2023). Further research is needed to determine whether these improvements translate into better fertility, pregnancy outcomes, or live birth rates.

GLP-1 receptor agonists are also associated with well-recognised adverse effects that may indirectly affect men trying to conceive. The most commonly reported side effects include nausea, vomiting, diarrhoea, constipation, and abdominal discomfort. In some individuals, these adverse effects can affect adherence to treatment or contribute to nutritional deficiencies if severe and prolonged. Rare but serious adverse events, such as pancreatitis and gallbladder disease, have also been reported, although these are uncommon (Davies et al., 2021).

Another consideration is that rapid weight loss associated with GLP-1 therapy may have complex effects on reproductive health. While weight reduction generally improves hormonal function and metabolic health in men with obesity, excessive or rapid weight loss can, in some circumstances, temporarily affect reproductive hormone balance. The extent to which this occurs in men receiving GLP-1 medications remains unclear due to the lack of dedicated fertility studies (Andersen et al., 2022).

Overall, there is currently no evidence demonstrating that GLP-1 medications negatively affect male fertility or pregnancy outcomes through paternal exposure. However, the absence of direct studies examining conception, pregnancy, and live birth outcomes means that uncertainty remains. Therefore, men who are planning to conceive should be counselled that the available evidence is limited and that further research is required to establish the reproductive safety of GLP-1 receptor agonists in this population.

References

Andersen, E., Juhl, C.R., Bonde, J.P. and Jensen, T.K. (2022). Weight loss and male reproductive function: a randomized controlled trial investigating semen quality following weight reduction in men with obesity. Human Reproduction, 37(1), pp.29–38.

Davies, M., Færch, L., Jeppesen, O.K., Pakseresht, A., Pedersen, S.D., Perreault, L., Rosenstock, J. and Wilding, J.P.H. (2021). Semaglutide 2.4 mg once a week in adults with overweight or obesity (STEP 1): a randomised, double-blind, placebo-controlled, phase 3 trial. New England Journal of Medicine, 384(11), pp.989–1002.

Varnum AA, Pozzi E, Deebel NA, Evans A, Eid N, Sadeghi-Nejad H, Ramasamy R. Impact of GLP-1 Agonists on Male Reproductive Health-A Narrative Review. Medicina (Kaunas). 2023 Dec 27;60(1):50. doi: 10.3390/medicina60010050. PMID: 38256311; PMCID: PMC10820247.

How do fertility specialists decide whether GLP-1 therapy is appropriate for men with obesity, metabolic disorders, or fertility concerns?

Fertility specialists determine whether GLP-1 therapy is appropriate on an individual basis by considering the patient's overall clinical picture rather than focusing solely on fertility concerns. This includes assessing factors such as body weight, metabolic health, medical history, current medications, lifestyle factors, reproductive history, and any underlying conditions that may affect fertility. For men with obesity or metabolic disorders, GLP-1 therapy may be considered as part of a broader strategy to improve overall health, particularly where weight loss and improved metabolic control could have indirect benefits for reproductive function. Decisions are typically made through shared decision-making, weighing the potential benefits against any risks or uncertainties, while taking into account the patient's fertility goals and personal circumstances.