Causal effects of hypertension on risk of erectile dysfunction: A two-sample Mendelian randomization study

Zheng Wang; Yunyun Wang; Jiachao Xiong; Xinxin Gan; Yewei Bao; Aimin Jiang; Ye Zhou; Zhao Huangfu; Yiren Yang; Zhiyong Liu; Demeng Xia; Linhui Wang

doi:10.3389/fcvm.2023.1121340

Causal effects of hypertension on risk of erectile dysfunction: A two-sample Mendelian randomization study

Front Cardiovasc Med. 2023 Mar 21:10:1121340. doi: 10.3389/fcvm.2023.1121340. eCollection 2023.

Authors

Zheng Wang¹, Yunyun Wang², Jiachao Xiong³, Xinxin Gan¹, Yewei Bao¹, Aimin Jiang¹, Ye Zhou¹, Zhao Huangfu¹, Yiren Yang¹, Zhiyong Liu¹, Demeng Xia⁴, Linhui Wang¹

Affiliations

¹ Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China.
² Department of Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
³ Department of Plastic and Reconstructive Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
⁴ Luodian Clinical Drug Research Center, Shanghai Baoshan Luodian Hospital, Shanghai University, Shanghai, China.

Abstract

Background: Erection dysfunction has been associated with hypertension in several epidemiological and observational studies. But the causal association between hypertension and erectile dysfunction requires further investigation.

Methods: A two-sample Mendelian randomization (MR) was conducted to analyze the causal effect of hypertension on risk of erection dysfunction. Large-scale publicly available genome-wide association study data were used to estimate the putative causality between hypertension and risk of erectile dysfunction. A total of 67 independent single nucleotide polymorphisms were selected as instrumental variables. Inverse-variant weighted, maximum likelihood, weighted median, penalized weighted median, and MR-PRESSO approaches were utilized in MR analyses. Heterogeneity test, horizontal pleiotropy test, and leave-one-out method were used to prove the stability of the results.

Results: In total, all P values were less than 0.05, demonstrating a positive causal link between hypertension and risk of erectile dysfunction in multiple MR methods, such as inverse-variant weighted (random and fixed effect) (OR 3.8315, 95% CI 2.3004-6.3817, P = 0.0085), maximum likelihood (OR 3.8877, 95% CI 2.3224-6.5081, P = 0.0085), weighted median (OR 4.9720, 95% CI 2.3645-10.4550, P = 0.0309), penalized weighted median (OR 4.9760, 95% CI 2.3201-10.6721, P = 0.0355), and MR-PRESSO (OR 3.6185, 95% CI 2.2387-5.8488, P = 0.0092). Sensitivity analysis detected no evidence of heterogeneity, pleiotropy, or outlier single nucleotide polymorphisms.

Conclusion: The study revealed a positive causal link between the presence of hypertension and the risk of erectile dysfunction. More attention should be paid during the management of hypertension with the purpose of preventing erectile dysfunction or improving erectile function.

Keywords: Mendelian randomization; PDE5 inhibitor; antihypertensive drug; erectile dysfunction; hypertension.