biostudies-literatureUnknown15Zhu Y<h4>Background</h4>Stroke is a devastating global health issue, with high mortality and disability rates. The increasing prevalence of male infertility among reproductive-aged men has become a growing concern worldwide. However, the relationship between male infertility and stroke incidence remains uncertain. This study aimed to address this knowledge gap by employing a Mendelian randomization (MR) approach.<h4>Method</h4>Utilizing genetic instrumental variables derived from a genome-wide association study (GWAS) on male infertility and stroke, a two-sample MR design was implemented. Five different analysis methods, with inverse-variance weighted as the primary approach, were used to examine the genetic causal associations between male infertility and various stroke subtypes. Heterogeneity analysis, pleiotropy tests, and leave-one-out validation were conducted to assess heterogeneity, evaluate pleiotropy, and ensure the robustness of the findings.<h4>Result</h4>The results indicate a potential lower risk of small vessel stroke associated with male infertility (odds ratio, 95% confidence interval: 0.82, 0.68 to 0.99, <i>p</i>=0.044), although no significant impact on other stroke subtypes was observed. The study exhibited low heterogeneity and no apparent pleiotropy; however, the stability of the results was not optimal.<h4>Conclusion</h4>Male infertility might potentially confer a protective effect against small vessel stroke risk. Caution is warranted due to potential confounding factors. Additional studies are necessary to confirm these findings and provide further validation.Frontiers in endocrinology1338077https://www.ebi.ac.uk/biostudies/studies/S-EPMC11056502biostudies-literatureCausal associations of male infertility with stroke: a two-sample Mendelian randomization study.PMC11056502Zhu YGuan SLiu QDong LXin XYu ZYe YWang JfalseCausal associations of male infertility with stroke: a two-sample Mendelian randomization study.<h4>Background</h4>Stroke is a devastating global health issue, with high mortality and disability rates. The increasing prevalence of male infertility among reproductive-aged men has become a growing concern worldwide. However, the relationship between male infertility and stroke incidence remains uncertain. This study aimed to address this knowledge gap by employing a Mendelian randomization (MR) approach.<h4>Method</h4>Utilizing genetic instrumental variables derived from a genome-wide association study (GWAS) on male infertility and stroke, a two-sample MR design was implemented. Five different analysis methods, with inverse-variance weighted as the primary approach, were used to examine the genetic causal associations between male infertility and various stroke subtypes. Heterogeneity analysis, pleiotropy tests, and leave-one-out validation were conducted to assess heterogeneity, evaluate pleiotropy, and ensure the robustness of the findings.<h4>Result</h4>The results indicate a potential lower risk of small vessel stroke associated with male infertility (odds ratio, 95% confidence interval: 0.82, 0.68 to 0.99, <i>p</i>=0.044), although no significant impact on other stroke subtypes was observed. The study exhibited low heterogeneity and no apparent pleiotropy; however, the stability of the results was not optimal.<h4>Conclusion</h4>Male infertility might potentially confer a protective effect against small vessel stroke risk. Caution is warranted due to potential confounding factors. Additional studies are necessary to confirm these findings and provide further validation.2024-01-01T00:00:00Z20242026-04-30T21:22:02.751Z2026-04-07T16:21:30.93ZS-EPMC110565023868620610.3389/fendo.2024.1338077