Bibliometric and Two-Sample Mendelian Randomization Analyses of the Causal Relationship Between Hypertension and Erectile Dysfunction

Summary

This study integrates bibliometric and two-sample Mendelian randomization analyses to systematically examine research trends and assess the causal relationship between hypertension and erectile dysfunction, identifying key contributors, emerging topics, and genetic evidence linking hypertension to increased erectile dysfunction risk.

Abstract

Hypertension (HT)-related erectile dysfunction (ED), a condition secondary to HT, is characterized by a persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. This study aimed to systematically analyze and visualize publications related to HT-related ED using bibliometrics to identify key topics, research hotspots, and knowledge gaps, and to explore the underlying causal relationship between HT and ED using Mendelian randomization (MR). Literature was retrieved from the Web of Science Core Collection, and publishing trends were profiled by country, institution, author, journal, and collaboration networks. For the MR analysis, single-nucleotide polymorphisms considerably associated with HT were selected, followed by pruning, filtering, and adjustment for potential confounders. The inverse variance weighting method was used as the primary analysis, complemented by MR–Egger and weighted median approaches, along with sensitivity analyses including heterogeneity and pleiotropy assessments to ensure robustness. Between 2001 and 2025, 1,661 articles were published in 1,099 journals, reflecting the evolving global research status and future directions. Academic institutions in Europe and North America have played a dominant role. The most prolific country, institution, journal, and author are the United States, University of São Paulo, Journal of Sexual Medicine, and Faix, A., respectively. Common keywords include nitric oxide, metabolic syndrome, and endothelial dysfunction. MR results confirmed that HT has a significant positive causal effect on ED risk. Research hotspots primarily involve impotence, oral sildenafil, vardenafil, safety, inhaled nitric oxide, international index, predictor, late onset hypogonadism, testosterone, obesity, oxidative stress, and phosphodiesterase 5 inhibitor. Two-sample MR provides robust causal evidence that supplements observational findings, offering a comprehensive framework for understanding HT-related ED.

Introduction

Hypertension (HT) is the predominant risk factor driving cardiovascular disease (CVD) development and mortality¹. CVD leads to nearly 17 million deaths globally each year, of which approximately 55% are attributed to complications of HT^2,3. Erectile dysfunction (ED) is characterized by persistent inability to achieve or sustain a penile erection adequate for satisfactory sexual activity⁴. Surveys have shown that, among patients with HT, the prevalence of ED ranges from 36% to 45%, which is significantly higher than that in non-hypertensive populations

Protocol

This study used publicly available data from the WOS database (https://www.webofscience.com/wos/woscc/basic-search) and did not involve human participants; therefore, ethical approval was not required.

Data Sources and Collection
The Web of Science (WOS) database is a widely recognized and frequently used resource for scientific and bibliometric research. It includes data from approximately 9,000 high-impact journals and over 12,000 academic conference proceedings, offering a comprehensive representation of global research across scientific, technological, medical, and related fields^16,

Results

Bibliometric Analysis Results
Time trends in publications and citations:
Annual publication output serves as a key indicator of research development and, to some extent, reflects the progression of knowledge within a field. As of December 20, 2025, a total of 1,661 publications related to HT-associated ED were identified in the Web of Science database (Figure 1). The yearly distribution of published articles is presented in Figure 2.

Discussion

By providing a comprehensive and systematic overview of the research topics, trends, and global landscape of HT-related ED, this study offers a rapid and preliminary understanding of the field. In the context of the big data era, it is increasingly important for researchers to recognize the developmental trajectory of their respective research areas. Compared with systematic reviews or meta-analyses, bibliometric analysis applies specialized visualization tools to comprehensively evaluate existing literature, allowing in.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
CiteSpace	Drexel University, USA	R6.1.3	RRID:SCR_025121
CMplot	Yin L, et al. rMVP: a memory-efficient, visualization-enhanced, and parallel-accelerated tool for genome-wide association study. Genom Proteom Bioinform. 2021;19(4):619-28.	4.5.1	NA
FinnGen dataset	FinnGen Consortium	Release 5	RRID:SCR_022254
gwasglue	MRCIEU, University of Bristol	0.0.0.9000	NA
IEU OpenGWAS platform	MRCIEU, University of Bristol	NA	NA
LDlink (LDtrait)	National Cancer Institute, NIH, USA	NA	RRID:SCR_011403
Microsoft Excel	Microsoft Corporation, USA	2021	RRID:SCR_016137
MR-PRESSO	Verbanck et al.	1	NA
R software	R Foundation for Statistical Computing, Austria	4.4.0	RRID:SCR_001905
TwoSampleMR	MRCIEU, University of Bristol	0.6.3	RRID:SCR_019010
VariantAnnotation	Bioconductor	1.50.0	RRID:SCR_000074
VOSviewer	Leiden University, Netherlands	1.6.18	RRID:SCR_023516
Web of Science Core Collection	Clarivate Analytics, USA	Accessed on December 20, 2025	RRID:SCR_005051