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The impact of cannabis use on erectile dysfunction and sex hormones: a Mendelian randomization analysis

Abstract

Previous study has highlighted an association between cannabis use (CU) and an increased risk of erectile dysfunction (ED), potentially due to indirect effects on sex hormonal balance. However, the evidence remains controversial, and the causal relationship is unclear. This study utilized genome-wide association study (GWAS) data to investigate the causal relationships between cannabis use disorder (CUD), lifetime cannabis use (LCU), and ED, as well as levels of sex hormones including estradiol (E2), bioavailable testosterone (BT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) through Mendelian randomization (MR) analysis. The primary method of analysis was the inverse variance weighted (IVW) method. Data from the FinnGen and UK Biobank were used for replication and meta-analysis. The results indicated no causal relationship between genetically predicted CUD (OR = 0.97, 95% CI 0.87–1.10, P = 0.66) and LCU (OR = 1.13, 95% CI 0.84–1.50, P = 0.42) with the risk of ED. The meta-analysis provided consistent evidence (P > 0.05). No causal relationships were found between CUD and LCU with E2(CUD: β = 0.00, 95% CI 0.00–0.01, P = 0.37; LCU: β = 0.00, 95% CI −0.02–0.01, P = 0.62), BT (CUD: β = 0.00, 95% CI −0.03–0.02, P = 0.90; LCU: β = 0.02, 95% CI −0.04–0.09, P = 0.46), FSH (CUD: β = 0.01, 95% CI −0.18–0.20, P = 0.92; LCU: β = 0.01, 95% CI −0.44–0.47, P = 0.95), and LH (CUD: β = 0.01, 95% CI −0.18–0.21, P = 0.90; LCU: β = 0.13, 95% CI −0.22–0.49, P = 0.46). Sensitivity analyses detected no evidence of horizontal pleiotropy or heterogeneity, ensuring the robustness of the results. In conclusion, this MR analysis did not provide evidence supporting a causal relationship between CU and ED or sex hormone levels.

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Fig. 1: Flowchart of Mendelian randomization analysis.
Fig. 2: Genetically predicted causal association of CUD and LCU on ED.
Fig. 3: Summary of the results of MR analysis of genetically predicted CUD and LCU on male sex hormones.

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Data availability

Data Statement: All data utilized in this article are derived from publicly accessible Genome-Wide Association Studies (GWAS). The datasets are fully accessible and can be obtained from the referenced articles cited within this document. Data for CUD are available from the Psychiatric Genomics Consortium (https://pgc.unc.edu/for-researchers/download-results/), data for LCU are available from the International Cannabis Consortium (https://www.ru.nl/bsi/research/group-pages/substance-use-addiction-food-saf/vm-saf/genetics/international-cannabis- consortium-icc/), UKB-ED can be downloaded from https://pheweb.org/UKB-SAIGE/, FinnGen-ED can be downloaded from https://www.finngen.fi/en, Bovijn-ED (ebi-a-GCST006956), E2 (ebi-a-GCST90012105), BT (ebi-a-GCST90012103), FSH (prot-a-528), LH (prot-a-529) can be downloaded from https://gwas.mrcieu.ac.uk/ according to the corresponding codes. Alternatively, summary GWAS data can be downloaded from https://www.ebi.ac.uk/gwas/ based on the corresponding PMID.

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Acknowledgements

We thank all GWAS participants and investigators for publicly making the summary statistics data available.

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Contributions

Youqian Zhang: Conceptualization: Led the conceptual design and development of the study’s research questions and methodology. Data curation: Played a key role in the acquisition and management of data used in the study. Formal analysis: Conducted the primary statistical analysis and interpretation of data. Writing - original draft: Was primarily responsible for drafting the manuscript. Yue Su: Methodology: Contributed significantly to the development and design of the Mendelian Randomization analysis methodology. Investigation: Assisted in the data collection and analysis process. Visualization: Created the figures and tables for the manuscript, ensuring accurate representation of the data. Zitian Tang: Software: Provided technical expertise in the use of software and tools for data analysis. Validation: Participated in the validation of the analysis to ensure the accuracy of results. Writing - review & editing: Contributed to the editing and revision of the manuscript for intellectual content. Lin Li (Corresponding Author): Supervision: Oversaw the entire research project, providing critical feedback and guidance to ensure its success. Writing - review & editing: Played a pivotal role in reviewing and editing the manuscript, ensuring coherence, and compliance with journal standards.

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Correspondence to Lin Li.

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Each investigation incorporated within the GWAS framework was sanctioned by the relevant ethical review panels Please see the original article citing the GWAS article for the specific approval documents. No ethics approval was necessary for this research.

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Zhang, Y., Su, Y., Tang, Z. et al. The impact of cannabis use on erectile dysfunction and sex hormones: a Mendelian randomization analysis. Int J Impot Res (2024). https://doi.org/10.1038/s41443-024-00925-3

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