The associations among platelet count, mean platelet volume, and erectile dysfunction: an observational and Mendelian randomization study.

Background: While previous studies have explored the associations and causalities among platelet count (PC), mean platelet volume (MPV), and erectile dysfunction (ED), further investigations are needed to clarify these relationships using advanced methodologies and analyzing specific populations.

Aim: To investigate the associations and causalities among PC, MPV, and ED using observational study and Mendelian randomization (MR) analysis.

Methods: A total of 114 patients with ED and 158 healthy control participants underwent a fasting blood draw to test for PC and MPV along with a comprehensive laboratory examination. The International Erectile Function Index was used to diagnose ED. Genetic variants of ED were obtained from individuals of European ancestry including 6175 ED cases and 217 630 controls. PC and MPV values were obtained from the UK Biobank and Investigating the effect of varying the whole blood inter-donation interval (INTERVAL) studies, encompassing a cohort of 173 480 individuals of European descent. Inverse-variant weighted (IVW), weighted median (WM), and MR-Egger methods were employed in MR analysis to explore the causal effects between variables to assess the impact of PC and MPV on ED. Various sensitivity analyses were employed to ensure the reliability of the results.

Outcomes: Both observational study results and MR results revealed that elevated PC levels were associated with a heightened risk of ED, whereas reductions in MPV were linked to a decreased risk.

Results: Logistic regression analysis indicated that an increased PC was associated with a greater risk of ED, with an odds ratio (OR) of 1.14 (95% CI: 1.08, 1.22; P = .005), whereas decreased MPV was linked to an increased risk for ED, with an OR of 0.65 (95% CI: 0.48, 0.88; P = .003). Our MR analysis also revealed that genetically predicted PC was associated with a 1.09-fold increased risk of ED (95% CI: 1.01, 1.18; P = .016). Conversely, genetically predicted MPV was linked to a 0.93-fold increased risk of ED (95% CI: 0.88, 0.99; P = .014). The absence of heterogeneity (P > .05) and pleiotropy (P > .05) was confirmed through Cochran's Q tests and MR-Egger regression. Exclusion of individual single-nucleotide polymorphisms (SNPs) did not alter the robustness of the results.

Clinical implications: In clinical work, it is an important guide for the prevention, diagnosis, and treatment of ED.

Strengths and limitations: Our study employed a combination of observational studies and MR studies to strengthen our evidence. The observational study's sample size was relatively small, and MR was limited to individuals of European ancestry.

Conclusion: A high PC and a low MPV are associated with an increased risk of ED, highlighting the importance of addressing platelet parameters in ED management.