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. 2025 Mar 26;13(1):qfaf014.
doi: 10.1093/sexmed/qfaf014. eCollection 2025 Feb.

Mendelian randomization analyses reveal causal relationships between chronic psychological stress and risk of erectile dysfunction

Wei Wang  1   2   3 , Bowen Tang  1 , Zhansen Huang  4 , Sushun Yuan  1 , Hongchen Luan  1 , Hengjun Xiao  4 , Jun Chen  1   2   3
Affiliations

Mendelian randomization analyses reveal causal relationships between chronic psychological stress and risk of erectile dysfunction

Wei Wang et al. Sex Med. .

Abstract

Background: The association between psychological stress and erectile dysfunction (ED) has been reported, but the causality of different types of stressors on ED is poorly understood.

Aim: This study aims to investigate the causal relationship between various forms of psychological stress and ED through Mendelian randomization (MR).

Methods: Several genome-wide association study (GWAS) datasets related to chronic psychological stress were used in this study for the identification of instrumental variables. Concurrently, a genome-wide association studies database provided the ED outcome data containing 6175 ED patients and 217 630 controls. The MR-Egger, inverse variance weighting (IVW), weighted median, and maximum likelihood methods were applied to conduct the MR study and IVW was taken as the primary criterion.

Outcomes: Mendelian randomization analyses revealed that financial difficulties were associated with a heightened risk of ED, whereas the absence of stressors was linked to a decreased risk.

Results: Among the various types of psychological stressors analyzed, financial difficulties were found to significantly increase the risk of ED (P = .022, OR = 4.343, 95%CI = 1.240-15.216). In contrast, other stressors did not significantly elevate the risk of ED. Furthermore, the absence of these stressors was associated with a reduced risk of ED (P = .009, OR = 0.211, 95% CI = 0.066-0.681).

Clinical implications: This study emphasizes the enormous impact of psychological stress, especially financial hardship, in increasing the risk of ED.

Strengths and limitations: This study is the first to employ MR analysis to investigate the causal relationship between various stressors and ED. However, this study did not consider the influence of non-genetic factors such as living environment and lifestyles.

Conclusion: Psychological stress, particularly financial difficulties, can increase the risk of ED, while the absence of such stressors appears to be protective. Consequently, it is imperative to enhance medical education and awareness among economically disadvantaged populations and to address the detrimental effects of adverse lifestyles.

Keywords: Mendelian randomization; erectile dysfunction; genome-wide association studies; psychological stress.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of Mendelian randomization between chronic psychological stress and erectile dysfunction. Assumption 1: There is a strong correlation between IVs and chronic psychological stress. Assumption 2: IVs are independent of confounders, including hypertension and diabetes, to influence ED. Assumption 3: IVs only influence the ED through the exposures. IVs, instrumental variables. ED, erectile dysfunction.
Figure 2
Figure 2
Forest plot of Mendelian randomization analysis results between various forms of psychological stresses and erectile dysfunction.
Figure 3
Figure 3
Scatter plots, forest plots, and funnel plots represent the corresponding risk relationships between SNPs of financial difficulties (A–C), absence of psychological stressors (D–F) and ED. SNP, single nucleotide polymorphism. ED, erectile dysfunction.
See this image and copyright information in PMC

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