Letter to the Editor on “The associations among platelet count, mean platelet volume, and erectile dysfunction: an observational and Mendelian randomization study”

To the Editor,

We read with great interest the article titled “The associations among platelet count, mean platelet volume, and erectile dysfunction: an observational and Mendelian randomization study,” which provides valuable insights into the relationship between platelet parameters and erectile dysfunction (ED).¹ However, we would like to offer several points of constructive feedback that could strengthen the study’s findings and improve its clinical relevance.

First, the study makes good use of MR techniques to reduce confounding bias, but the authors do not explicitly state how potential confounders were considered in the MR analyses. One of the three main hypotheses of MR, that the instrumental variable (IV) used is independent of confounders and affects the results only through exposure, is central to the validity of the results. However, the manuscript does not discuss in detail how to consider or control for potential confounders such as lifestyle factors (e.g., diet, physical activity), comorbidities, and environmental influences.² And these factors may be important in influencing the relationship between platelet parameters and ED. In addition, the lack of discussion of gene–environment interactions is an important limitation. Future studies should address these potential confounders, either by explicitly adjusting for these factors in the MR framework or by performing sensitivity analyses to assess their impact on outcomes.

Secondly, the current MR analysis in the manuscript investigates the relationship between platelet count and MPV and ED using single-exposure models. While this approach provides useful insights, it overlooks the potential interactive effects between multiple platelet parameters. Given that both platelet count and MPV are independently associated with ED risk, multivariate MR or mediator MR analyses can provide a more comprehensive understanding of how these two factors work together to influence ED.^3,4 The current analysis treats platelet count and MPV as isolated exposures, which may oversimplify the complex interplay between these markers. Incorporating a multivariable approach would enhance the robustness of the findings and provide a clearer picture of how these platelet parameters contribute to ED risk in combination.

Latest, the manuscript categorizes ED as a binary outcome, which may oversimplify the complexity of ED. ED varies in severity, and the relationship between platelet parameters and ED may differ across different stages of the condition. Future research should consider stratifying ED by severity to better understand how platelet count and MPV influence the progression of ED. Such an analysis could provide more detailed insights into the specific role of platelet parameters in mild versus severe cases of ED and help identify potential interventions for different stages of the disease.

In conclusion, the authors’ work on the relationship between platelet count, MPV, and ED provides an important contribution to the field. We hope the authors will consider these suggestions in their future work, which could further elucidate the role of platelet parameters in ED and potentially guide therapeutic interventions.

Acknowledgments

None.

Author contributions

All authors contributed to the study conception and design. Study design, YKF, SYC, CXH, Writing-original draft, YKF, CXH; Writing-review & editing, YKF, CXH, BC; Supervision: BC.

Funding

This research received no external funding.

Conflicts of interest

None of the authors has any conflicts of interest.

References