Global research trends in the comorbidity of erectile dysfunction and premature ejaculation: a 20-year bibliometric analysis [2005–2025]

Introduction

Erectile dysfunction (ED) and premature ejaculation (PE) are the two most prevalent conditions within male sexual dysfunction (1,2). They frequently coexist in clinical practice, with comorbidity rates reported between 23% and 29%, particularly among middle-aged and elderly men or those with conditions such as diabetes (3,4). This high coexistence suggests that ED and PE may constitute risk factors for each other, with emerging perspectives proposing that they be treated as highly interrelated symptoms of a previously undescribed condition rather than entirely distinct disorders (5,6). This shift underscores underlying mechanisms that are complex and interactive.

Substantial research has focused on pathophysiological pathways, which span neurobiological (e.g., NO and 5-HT systems), vascular, endocrine, and psychosocial domains (7-10).

In the clinical management of ED/PE comorbidities, the efficacy of first-line drug therapy regimens—with phosphodiesterase type 5 (PDE5) inhibitors (e.g., tadalafil) combined with selective serotonin reuptake inhibitors (SSRIs; e.g., dapoxetine) as the core—has been confirmed (11). Traditional Chinese medicine (TCM) and acupuncture have also shown potential value in this integrated model (12,13). Integrated treatment strategies should also incorporate psychobehavioral interventions (e.g., cognitive behavioral therapy and emerging virtual reality technologies) (14,15), and physical therapy for pelvic floor muscle dysfunction to synergistically improve erectile function, ejaculation control, and related psychological distress (16,17).

Numerous studies have now focused on the mechanisms, etiological factors, and treatment of comorbid ED and PE, but they remain fragmented. This fragmentation highlights a significant gap: a comprehensive, quantitative synthesis of the research landscape is lacking. Traditional narrative or thematic reviews are limited in objectively revealing research priorities, collaboration networks, and potential structural imbalances.

Against this backdrop, bibliometric methods provide a vital tool for systematically assessing the developmental dynamics, knowledge structure, and frontier trends within a specific research domain.

Through quantitative analysis of fundamental characteristics such as publication dates, geographical distribution, journals, authors, and institutions, this study identifies research hotspots, core literature, and knowledge networks within the field. It seeks to address the following questions: (I) how has the knowledge structure of ED/PE comorbidity research evolved over time? (II) What are the key clinical and scientific factors driving this evolution? (III) What potential blind spots and imbalances exist in current research? (IV) Which future directions hold the greatest translational potential? We present this article in accordance with the BIBLIO reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0302/rc).

Methods

Data retrieval and collection

Web of Science is the most widely used database in scientific and bibliometric research. It encompasses nearly 9,000 of the world’s most influential journals and over 12,000 academic conferences, providing a comprehensive overview of research outputs across global science, technology, medicine, and other disciplines (18).

This paper is based on publications retrieved from Web of Science Core Collection (WoSCC). As only seven documents were available prior to 2005, the search period was restricted to January 1, 2005 to December 31, 2025. The search query was confined to the “topic” field. The screening process included only original articles and review articles written in English. The retrieval results were exported in plain text format as a plain text file, with content set to “full records and cited references”. Search strategies encompass the following topics: ((“erectile dysfunction” OR “erectile disorder” OR “impotence” OR “male sexual dysfunction”) AND (“premature ejaculation” OR “rapid ejaculation” OR “early ejaculation” OR “lifelong premature ejaculation” OR “acquired premature ejaculation” OR “intravaginal ejaculatory latency time” OR “IELT”)). Following screening, a total of 1,089 articles were identified. The search diagram is shown in Figure 1.

Figure 1 A process flowchart. SCIE, Science Citation Index Expanded; WoSCC, Web of Science Core Collection.

Statistical analysis

This study primarily employs VOSviewer (version 1.6.20), CiteSpace (version 6.3.R1), the Bibliometrix software package (version 4.5.2), and the online bibliometric analysis platform (https://bibliometric.com/) for bibliometric analysis and visualization.

VOSviewer is a powerful visualization tool that enables us to import literature data from the Web of Science database. Leveraging its diverse data source compatibility, co-occurrence analysis, clustering analysis, and timeline view capabilities, it facilitates in-depth analysis (19). By leveraging insights from visual analysis, we can highlight keywords, identify knowledge development timelines and emerging trends, thereby gaining clearer insights into researchers’ developmental characteristics (20).

CiteSpace is a widely recognised visual analysis software within the field of bibliometrics (21). Identifying core literature, research collaboration networks and research hotspots through CiteSpace software (22).

Bibliometrix is an R package for bibliometric analysis of scientific literature, supporting data import from multiple databases to dissect research within the field across various dimensions. Its comprehensive co-citation analysis, which excludes journals with fewer than 20 citations, yields significant insights (23).

Data preprocessing and parameter settings

To improve reproducibility and reliability, several data-cleaning and standardization procedures were performed before visualization.

First, duplicate records from the WoSCC were removed using Bibliometrix, retaining only one copy per duplicate entry. Second, author names and institutional affiliations were manually standardized to correct inconsistencies (e.g., “Univ Rome Tor Vergata” vs. “University of Rome Tor Vergata”), and country names were unified according to Web of Science indexing. Third, synonymous terms and spelling variants (e.g., “erectile dysfunction” vs. “ED”; “premature ejaculation” vs. “PE”) were merged to improve co-occurrence accuracy.

For VOSviewer, full counting and association-strength normalization were applied. The minimum publication threshold for country collaboration analysis was set at five documents, and the minimum citation threshold at two citations. For keyword co-occurrence analysis, only keywords appearing more than five times were included.

For CiteSpace, the time slicing was set from 2005 to 2025 with 1-year intervals. The g-index selection criterion (k=25) was applied per slice, and pathfinder pruning was used to simplify networks and highlight key relationships.

Bibliometrix (version 4.5.2) was used for descriptive statistics, Bradford’s law analysis, author productivity analysis, and thematic evolution analysis. All analyses used default software settings unless otherwise specified.

These procedures improved data consistency, reduced ambiguity, and enhanced workflow reproducibility.

Results

Annual analysis of global publications

In accordance with the established methodology, this study screened and analyzed 1,089 papers concerning ED and PE as illustrated in Figure 1 (generated using Word software). Exclusions comprised excluding meeting abstract (N=40), editorial material (N=13), letter (N=12), proceeding paper (N=10), book chapters (N=9), correction (N=3) and retracted publications (N=1), after selecting article and review article. The final analysis comprised 858 original articles (77.65%) and 231 reviews (22.35%).

Figure 2, reviews two decades of data, showing an exponential and sustained annual increase in total publications, with the fitted exponential equation exhibiting a high coefficient of determination (R²=0.6479).

Figure 2 Trend chart of annual publication volume of ED and PE from 2005 to 2025 (generated with RStudio and Excel). ED, erectile dysfunction; PE, premature ejaculation.

The chart indicates that 2008 and 2021 represent pivotal points for significant growth. Publication output showed a marked increase around 2008. This period coincided with increased scholarly attention to dapoxetine and pharmacological management of PE/ED comorbidity. A further increase in publication activity was observed around 2021, alongside growing interest in low-intensity shockwave therapy (Li-ESWT) and regenerative medicine-related interventions in the literature (24-26).

National and institutional analyses

According to Bibliometrix statistical analysis, a total of 55 countries and 1,073 institutions have conducted research on ED and PE. Table 1 lists the top ten countries by total number of publications. As shown in Table 1 (data obtained from corresponding author’s countries in RStudio software), China produced the highest number of papers (N=149), accounting for 13.7% of global publications. Subsequently, ranked by publication volume and proportion, are the United States (N=148, R=13.6%), Italy (N=124, R=11.4%), and Turkey (N=104, R=9.6%). These nations account for nearly half of the world’s total publications, underscoring their influence in this field. As shown in Figure 3 and Table 1, although China leads globally in publication volume, its proportion of multi-country collaborative publications remains low (R=12.1%). Among the top ten countries by publication volume, China’s proportion of multinational collaborative publications falls significantly below that of the United States (R=22.3%) and Italy (R=25.0%). In contrast, Australia (R=51.9%), the United Kingdom (R=37.1%) and Germany (R=37.0%) exhibit a higher proportion of multinational collaborative publications, indicating these nations engage in frequent research interactions with other countries.

Figure 3 Top 10 most productive countries (from corresponding author’s country in RStudio software). MCP, multiple country publications; SCP, single country publications.

Figure 4 depicts the international collaboration network diagram for 41 standardized countries in this field, generated by setting minimum publication thresholds of 5 papers and minimum citation thresholds of 2 citations. Node size represents a country’s publication volume, with China, the United States, Turkey, the United Kingdom, and Italy exhibiting the largest nodes as the primary knowledge-producing nations in the ED and PE domains. The United States holds the highest total link strength at 287, followed by Italy at 249 and the United Kingdom at 209, indicating these three nations exert significant influence in international collaboration. China’s total link strength is 36. The thickness of connections indicates frequent collaboration primarily with Italy, while node colour suggests alignment in research themes with the United States. China exhibits substantial publication output in this field but commenced research later than other international players.

Figure 4 National cooperation network diagram (from VOSviewer software national collaborative analysis).

Figure 5 depicts citation burst detection for the top 15 institutions. Overall, Pfizer, the University of Rome Tor Vergata, and Hôpital Universitaire Raymond-Poincaré – APHP are the institutions with the most prominent burst intensity. In recent years, Eötvös Loránd University, Anhui Medical University, and Sun Yat-sen University have been highly active, reflecting growing scholarly interest in these institutions.

Figure 5 Top 15 institutions with the strongest citation bursts (presents the results of institution burst detection using CiteSpace).

Analysis of journals

A total of 327 academic journals contributed to the publication of relevant papers. Analysis of the top ten journals (Table 2) reveals that the Journal of Sexual Medicine published the highest number of papers (N=195) and also recorded the highest citation count (N=7,239). Furthermore, in terms of average citations, BJU International recorded the highest figure. Its impact factor (IF =4.4) and 2025 journal citation reports (JCR) division (Q1) also place it at the forefront, underscoring its academic influence and value within the field.

Figure 6 illustrates that journals within Bradford’s “core zone” have published a substantial volume of high-quality literature in this domain. The horizontal axis represents source log(rank), indicating the logarithmic rank of sources sorted by publication output. The vertical axis represents the cumulative number of articles. The black curve shows the actual cumulative publication distribution, while the red dashed line represents the fitted curve based on Bradford’s law. Approximately five core journals in the figure account for the majority of the literature output in this field, whereas the remaining articles are progressively dispersed across 40 sub-core sources and 282 peripheral sources.

Figure 6 Analysis of academic journals related to ED and PE (from RStudio software). ED, erectile dysfunction; PE, premature ejaculation.

Author contributions and co-occurrence

A total of 3,987 scholars contributed to publications in this field. According to Table 3 (sorted by h-index), Jannini EA has the highest number of publications (N=50). Corona G ranks seventh with 23 papers but leads in total citations (N=1,044). Notably, Rowland DL, with only 27 papers, has a fractionalized count of 10.09, indicating a predominance of sole-authored or small-team publications. In contrast, Sansone A, despite having 18 papers, has a fractionalized count of only 2.63, suggesting he typically participates as a co-author in large collaborative studies.

Figure 7 illustrates the collaborative relationships among 76 authors, requiring a minimum of five published papers. They are grouped into nine distinct collaborative clusters, with node size representing co-occurrence frequency and links indicating co-authoring relationships. The deep blue, light blue, red, orange, and green clusters exhibit strong internal collaboration, with interactions between these groups occurring more frequently than with others.

Figure 7 Authors co-occurrence graph (from VOSviewer software).

Citation and reference analyses

Table 4 lists the top ten most cited publications, all from journals of considerable standing. The top-ranked paper, “Guidelines on Male Sexual Dysfunction: Erectile Dysfunction and Premature Ejaculation” by Hatzimouratidis K, published in Eur Urol in 2010, has been cited 779 times. It provides a systematic review of literature concerning the epidemiology, diagnosis, and treatment of ED and PE, establishing a framework for their clinical management. Ranked second is Lewis RW’s 2010 article “Original Articles: Definitions/Epidemiology/Risk Factors for Sexual Dysfunction” in J Sex Med, cited 646 times. This paper provides an overview of definitions, incidence, and prevalence of male and female sexual dysfunction, alongside risk factors identified in large population-based studies (27).

Figure 8 displays 20 core papers exhibiting significant citation surges, reflecting their academic influence and emerging research trends within the fields of PE and ED. Early foundational literature, including studies by Laumann et al. (28), utilized the Global Survey of Sexual Attitudes and Behaviours (GSSAB)—an international survey examining sexuality and interpersonal relationships in adults aged 40–80 years. These studies ultimately concluded that sexual issues in men are typically associated with physical health and aging, while such concerns are more pronounced in women. A four-week multicenter observational study investigated the understanding and perceptions of PE among men and their female partners in monogamous relationships. Citations of these studies surged between 2005 and 2010.

Figure 8 Top 20 references with the strongest citation bursts (from CiteSpace, burst analysis of cited literature).

McMahon et al. (29) published a paper in The Journal of Sexual Medicine in 2008, which was significantly cited between 2009 and 2013. Serefoglu et al. (30) and Althof et al. (31) published papers in The Journal of Sexual Medicine in 2014. Both articles experienced a significant surge in citations between 2015 and 2019.

Salonia et al. (7) published the “European Association of Urology Guidelines on Sexual and Reproductive Health—2021 Update: Male Sexual Dysfunction” in European Urology in 2021, updating the definitions, diagnosis, and treatment of male sexual dysfunction (including ED and PE). As society evolves and pharmaceutical research advances, the definitions and treatments for such conditions continue to evolve.

Figure 9 employs co-citation clustering analysis to objectively present the knowledge structure within the research domain. Research themes are categorized into 18 distinct clusters based on citation co-occurrence relationships, forming a clear clustering pattern. Research hotspots have also undergone continuous evolution over time.

Figure 9 Reference clustering analysis diagram based on similarity (from CiteSpace co-citation clustering analysis).

Cluster 1 (PE patient) and Cluster 3 (narrative review) in the diagram represent foundational and methodological literature constituting early research, subsequently shifting towards more focused review and expanded research directions such as Cluster 4 (systematic review), Cluster 5 (sexual desire), and Cluster 6 (PE).

Ultimately, research further differentiated and deepened into a series of clinical themes, including Cluster 0 (lifelong PE), Cluster 2 (evidence-based definition), Cluster 7 (phosphodiesterase type), Cluster 8 (type-5 phosphodiesterase inhibitor), and Cluster 9 (aging male), illustrating the recent diversification of PE and ED research.

Cluster 10 (PRISMA-compliant systematic review), Cluster 11 (sexual medicine guideline), Cluster 12 (novel treatment), Cluster 13 (counseling patient), Cluster 14 (coming from), Cluster 15 (physician’s perspective), Cluster 16 (Chinese herbal medicine), and Cluster 17 (symptom) remain marginalized, necessitating strengthened connections within these research directions.

Keyword analyses

Figure 10 presents a network visualization for keyword co-occurrence analysis (n>5). Each node within the network represents a keyword, with node size indicating the frequency of its occurrence. Larger nodes denote higher keyword frequency. The figure reveals that the most frequent keywords include “premature ejaculation”, “prevalence”, “erectile dysfunction”, and “double-blind”.

Figure 10 Keyword collaboration network diagram [from VOSviewer presents a network visualization for keyword co-occurrence analysis (n>5)].

Figure 11 demonstrates the evolution of PE and ED keywords. The relative prominence of these themes fluctuates significantly over time, with larger nodes indicating higher frequency and importance. Between 2016 and 2018, terms such as “erectile dysfunction”, “prevalence”, “men”, and “premature ejaculation” appeared frequently, with research predominantly investigating the epidemiological characteristics of PE and ED. In recent years, keywords such as “cognitive behavioral therapy”, “traditional Chinese medicine”, “pathophysiology”, “latency”, “associations”, “risk”, and “validation” have gained prominence, indicating a gradual deepening of current research directions.

Figure 11 Keyword trend chart (from RStudio demonstrates the evolution of PE and ED keywords). ED, erectile dysfunction; PE, premature ejaculation.

Figure 12 analyzes the outbreak trends of keywords from 2005 to 2025 (the blue line denotes the timeline; red segments indicate the start year, end year, and duration of each outbreak). Keywords such as “validity”, “complaint”, “guidelines”, and “sexual function” are projected to experience outbreak phases in recent years.

Figure 12 Top 25 keywords with the strongest citation bursts (from CiteSpace analyzes the outbreak trends of keywords from 2005 to 2025).

Figure 13 visualizes the temporal evolution of key research themes in this field. The significance of each keyword fluctuates over time, with larger, more concentrated nodes indicating higher frequency and importance. Keywords are organized into clusters on the right side of the diagram, which categorizes them into 12 groups chronologically, revealing that the most recent and prevalent keywords are “premature ejaculation”, “prevalence”, and “erectile dysfunction”. During the early period from 2005 to 2013, keywords such as “rapid ejaculation”, “paroxetine”, “sertraline”, “sildenafil”, “sexual disorders”, “health surveys”, and “population” experienced a surge. The clinical application of sertraline and sildenafil became research focal points in 2005 (32,33).

Figure 13 Keyword trend chart with highlighted timeline (generated from CiteSpace, visualizes the temporal evolution of key research themes in this field).

Discussion

The overall landscape of ED/PE comorbidity research

The bibliometric analysis in this study reveals the developmental trajectory of the field of ED-PE comorbidity. Over the past two decades, research on the co-occurrence of ED and PE has demonstrated a sustained upward trend and remains in a phase of rapid expansion.

From a temporal perspective, this field has exhibited sustained and accelerating exponential growth since 2005 (Figure 2), with two pivotal inflection points. These temporal patterns may reflect shifting research interests in response to emerging therapeutic strategies, including dapoxetine, Li-ESWT, and regenerative medicine. However, because no formal segmented trend analysis was performed, these associations should be interpreted cautiously as literature-level temporal correspondences rather than confirmed drivers of publication growth. This indicates that innovations in therapeutic approaches are temporally associated with research momentum. Moreover, the steep trajectory projected from 2021 to 2025 suggests that research into the co-morbidity of ED and PE will deepen and expand significantly in the coming years.

From an international perspective, a dominant structure has emerged, centered on China as a high-output country and on the United States and Italy as high-influence and collaborative hubs. China leads in total publications (N=149, 13.7%), yet the United States and Italy play pivotal roles in shaping international research and guideline development through greater international collaboration intensity (total link strengths of 287 and 249, respectively) and higher citations per paper.

The discrepancy between “output” and “impact” warrants reflection. While China leads in total publication volume, the breadth of its international research collaborations and average citation impact still lag behind traditional powerhouses such as the United States and Italy. This may reflect differences in research types. Chinese research may be more inclined towards regional clinical observations or large-scale epidemiological surveys, whereas European and American studies dominate multinational multicentre clinical trials, fundamental mechanism exploration, and international guideline development. For Chinese scholars, the future lies in maintaining output scale while deepening integration into international collaborative networks and focusing on foundational and translational research that produces universal theories or pioneering therapies.

From the perspective of knowledge carriers, research is highly concentrated on a small number of high-impact platforms. The Journal of Sexual Medicine serves as the core publication outlet, while BJU International, with its notable IF (4.4) and average citation (N=57), has become a primary vehicle for publishing guidelines and consensus documents that establish the field’s paradigms (Table 4). Combining keyword analysis with highly cited literature reveals a clear evolution in research themes. Initial focus on disease definition, epidemiological studies, and single-drug trials has progressed to in-depth exploration of comorbid mechanisms, combined treatment regimens, and multi-modal integrated interventions.

From the perspective of core academic research strength, Jannini EA (50 papers) and Corona G (total citations 1,044) stand as the most influential researchers in this field. Their work centers on hormonal and psychological interaction mechanisms in male sexual dysfunction, the comorbidity between PE and ED, and optimizing treatment strategies. Maggi M and McMahon CG have made significant contributions in areas including pharmacological treatment trials, guideline revisions, and the validation of dapoxetine efficacy (34-36). Hellstrom WJG, Serefoglu EC, Giuliano F, Lenzi A, and colleagues—representing research institutions from the United States, Turkey, Italy, and other nations—have established a comprehensive research network encompassing pathophysiological mechanisms, behavioral interventions, and cross-disease association studies. The collaboration and high-caliber output of this group have facilitated the updating of international medical association guidelines and the establishment of unified standards, thereby advancing clinical practice towards evidence-based approaches.

Evolution of research focus

By integrating the keyword timeline, emergent terms, highly cited publications, and cluster analysis, we can identify three significant shifts in the research focus concerning the co-occurrence of ED and PE.

Definition and epidemiological stages [2005–2013]

The core focus of research during this period was establishing concepts, conducting epidemiological investigations, and validating the efficacy of single-agent therapies. Highly cited publications predominantly centered on developing evidence-based definitions, diagnostic criteria, and epidemiological reviews for ED and PE, such as those by Hatzimouratidis et al. (3); Lewis et al. (27); and Laumann et al. (28).

Keyword salience analysis indicates that specific drug names such as “sildenafil”, “sertraline”, and “paroxetine” emerged as burst keywords during this period, coinciding with the peak phase of clinical trials for PDE5 inhibitors and SSRIs (32,33). Research patterns primarily focused on describing comorbid phenomena and validating monotherapies, thereby establishing methodological and epidemiological foundations for subsequent studies.

Mechanism exploration and combined therapy phase [2014–2020]

The research focus shifted towards understanding the complex mechanisms of comorbidity and optimizing clinical practice. Citations of guidelines and consensus documents peaked during this phase (30,31), signaling the field’s entry into a standardization stage. Among keywords, “risk factor” and “association” emerged as new focal points, with research systematically examining the roles of psychological factors, metabolic disorders, endocrine dysregulation (37,38), and lifestyle factors in comorbidity. Concurrently, “combination therapy” gained prominence, reflecting a shift in clinical translation efforts from monotherapy towards strategies such as the co-administration of PDE5 inhibitors and SSRIs (8,9).

Diversification and integration intervention phase [2021–present]

Recent research exhibits characteristics of interdisciplinary integration and diversification of therapeutic approaches. Keyword emergence analysis indicates that “cognitive behavioral therapy”, “pathophysiology”, and “validation” have emerged as new frontiers (14,15). This signifies that research has transcended the purely biomedical model, deeply integrating psychological and behavioral interventions with investigations into underlying mechanisms. Concurrently, emerging physical and regenerative therapies—such as Li-ESWT (25) and platelet-rich plasma (PRP) (39)—have synchronized with growth nodes in research output, emerging as novel therapeutic research focal points. Moreover, sustained focus on “meta-analysis” and “guidelines” (40), alongside the application of artificial intelligence for risk prediction (41), collectively signals the field’s progression towards evidence integration, standardized diagnostics, and precision medicine. Peripheral clusters in the analysis, such as “hormonal control” and “patient counseling”, explicitly point to future potential in integrating endocrine regulation with patient-centered psychosocial interventions.

Driving forces behind the evolution of research paradigms: clinical needs, therapeutic innovation and academic synergy

Firstly, the persistently growing unmet clinical need stands as one of the core drivers behind the paradigm shift in research. Early studies treated ED and PE as distinct conditions. As epidemiological data accumulated (4), the academic community recognized that comorbidity represents the norm rather than the exception. This paradigm shift has compelled the research focus to transition from single-drug efficacy towards combined medication strategies, interaction mechanisms, and comprehensive management protocols. Research has recognized that psychological factors (anxiety, depression) are not merely outcomes but central mechanisms sustaining comorbidity. This has propelled non-pharmacological interventions—such as cognitive behavioral therapy and partner-involved treatment—to the forefront.

Secondly, key therapeutic advances have reshaped research paradigms. Dapoxetine, the first drug approved specifically for PE, opened a new research landscape (24) and spurred numerous clinical studies on combination therapy safety, efficacy, and dosing. Long-acting PDE5 inhibitors (e.g., tadalafil) enhance erectile function by inhibiting cyclic guanosine monophosphate (cGMP) degradation and promoting cavernosal smooth muscle relaxation, shifting treatment from “on-demand” to “regular” therapy and offering greater pharmacological flexibility for managing comorbidities. Meanwhile, novel techniques such as low-intensity extracorporeal shock wave therapy and PRP injections directly improve the penile vascular endothelium, providing new options for patients unresponsive or intolerant to drug therapy and opening fresh avenues for research.

Finally, academic organizations and clinical guidelines have played a crucial guiding role in the evolution of research paradigms. Regular updates to authoritative guidelines from bodies such as the European Association of Urology (EAU) and International Society for Sexual Medicine (ISSM) have systematically identified comorbidities as clinical challenges and prioritized them as key research areas. These recommendations steer the research focus and funding allocation of global investigators, as illustrated in Figure 8 and Table 4, where guideline-related literature forms the core. Highly productive and influential scholars, exemplified by Jannini EA and Corona G, form the academic core (Figure 7). Through collaborative networks, they spearhead large-scale clinical studies, define standards, and draft consensus documents, advancing field-wide consensus. Journals such as the Journal of Sexual Medicine (Table 3) have established the research paradigm and discourse authority within the field by publishing high-quality studies, thereby attracting further scholarly participation.

Bibliometric signals and literature-informed interpretation of ED/PE comorbidity

Bibliometric findings related to mechanistic themes

Bibliometric analyses in the present study indicate that research on ED-PE comorbidity has progressively moved beyond isolated disease descriptions toward more integrative themes that involve pathophysiology, combined treatment strategies, psychological intervention, and validation-related topics. Keyword evolution, co-citation clustering, and recent burst terms suggest increasing academic attention to the interplay among neurobiological, vascular, and psychological dimensions in this field. These findings reflect shifts in thematic convergence and scholarly focus within the literature, rather than direct evidence of a unified pathophysiological mechanism.

Author interpretation: a literature-informed neuro-vascular-psychological framework

The following framework is presented as an author interpretation informed by bibliometric patterns and prior mechanistic literature, rather than as a direct finding of the present bibliometric analysis.

Neural modulation node

Ejaculation control is primarily governed by the central nervous system’s 5-HT pathways, which act as a “higher-order regulator” by establishing inhibitory thresholds that determine the timing of the ejaculatory reflex (42). Current literature suggests that insufficient inhibitory control of the central serotonin (5-HT) system over the ejaculatory reflex may contribute to PE (43). Erectile function primarily relies on the peripheral NO/cGMP pathway in the penile corpus cavernosum, which directly regulates vascular smooth muscle relaxation and engorgement (44). Smooth muscle relaxation dilates the cavernous sinuses, allowing substantial arterial blood influx. Concurrently, the dilated corpora compress subalbuginal veins, obstructing venous outflow. The penis rapidly engorges, hardens, and sustains erection. PDE5 degrades cGMP, reducing its concentration, allowing smooth muscle to contract again and causing the erection to subside.

Although the physiological processes of erection and ejaculation are relatively independent, they are intricately intertwined through complex neurobiological networks in the central nervous system, spinal cord, and periphery. Sexual arousal signals reach the brain and then travel via descending spinal pathways (e.g., the spinal pelvic pathway) to influence pelvic organs. This process requires precise coordination between parasympathetic signals that promote erection and 5-HT inhibitory signals that control ejaculation. Disruption in higher centers (e.g., anxiety or depression) weakens the descending control of both signals. The lumbosacral spinal cord serves as the primary reflex center for both functions, housing shared interneuron populations that connect to lower-level neurons regulating erection and those governing ejaculation (17).

This may provide a conceptual basis for understanding how the two systems are linked at the spinal cord level. Functionally, intense afferent signals from the ejaculatory reflex can inhibit the autonomic output that sustains erection via spinal intrinsic interneurons. Pathologically, chronic hyperactivation of one system (e.g., the ejaculatory reflex) may persistently interfere with the other (e.g., erection maintenance) through this shared or mutually inhibitory spinal interneuron network. This could represent a neural framework for ED-PE comorbidity.

Vascular and endothelial dysfunction node

Vascular endothelial dysfunction is the core mechanism of organic ED and serves as the bridge linking ED and PE to systemic diseases such as diabetes, hypertension, and metabolic syndrome. It also plays a key role in the pathogenesis of PE. Insufficient arterial blood supply or impaired venous occlusion may increase the intensity and duration of stimulation needed to achieve an erection, directly exacerbating performance anxiety and fear, thereby triggering or worsening PE. Chronic pelvic pain, prolonged sitting, or incorrect sexual behavior patterns can lead to excessive pelvic floor muscle tension. Hypertonic pelvic floor muscles may compress penile vessels or nerves, impairing erectile rigidity; simultaneously, their abnormal tension during sexual arousal accelerates reaching the ejaculatory threshold. Pelvic floor physical therapy has been shown to improve sexual dysfunction (45). Endothelial dysfunction frequently accompanies systemic low-grade inflammation and oxidative stress. These factors not only damage blood vessels but may also impair autonomic and sensory nerve function in pelvic organs, linking ED and PE through neurovascular coupling. This explains why lifestyle interventions (e.g., the Mediterranean diet and exercise) can improve both dysfunctions simultaneously (9).

In recent years, physical and regenerative therapies such as Li-ESWT and PRP have gained prominence. Their core mechanism lies in directly acting upon the vascular endothelium, reversing the pathological basis of vascular ED by upregulating vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expression and promoting neovascularisation.

Psychological and behavioural nodes

Psychosocial stress serves both as a common precipitating factor and a significant consequence, concurrently diminishing serotonin’s inhibitory function, lowering the ejaculatory threshold, and heightening sympathetic tone. This antagonizes nitric oxide’s vasodilatory effects, thereby simultaneously inducing or exacerbating symptoms of both ED and PE, creating a vicious cycle of mutual deterioration. Chronic stress or anxiety elevates central noradrenergic tone, which concurrently inhibits serotonergic function, exacerbates PE, and intensifies sympathetic vasoconstriction in penile vessels, thereby inducing or worsening ED.

Limitations

This study has several limitations. First, the search was limited to the WoSCC and English-language literature, which may have excluded other databases (such as PubMed, Scopus, Embase, and Chinese databases) and non-English studies, potentially introducing language and database bias. Second, variations in database update frequency, indexing delays, and differences in the categorization of early online publications may also lead to data fluctuations. Finally, bibliometric methods themselves have inherent limitations. Search string settings, terminology differences, and inconsistent keyword labels may result in the omission of relevant literature and affect the accuracy of topic clustering and co-occurrence analysis. Citation analysis is also influenced by self-citation and citation lag from authors or journals, which may amplify or underestimate the academic impact of some studies. More importantly, publication activity and citation frequency primarily reflect knowledge dissemination and academic attention and cannot be equated with clinical efficacy or research quality. Therefore, the results of this study cannot replace efficacy evaluations based on meta-analyses and high-quality clinical trials.

Conclusions

This study employed bibliometric methods to analyze the knowledge structure and developmental trajectory of research on ED-PE comorbidity over the past two decades. The findings show that the field has progressively shifted from an early single-disease focus toward a more integrated, comorbidity-oriented research paradigm, with growing attention to comprehensive management and mechanistic links. Nevertheless, the field is still developing and has not yet reached full maturity. Importantly, the present bibliometric analysis reflects patterns of thematic evolution and scholarly attention rather than direct clinical or mechanistic evidence. Therefore, the conceptualization of ED-PE comorbidity within a neuro-vascular-psychological framework should be considered a literature-informed hypothesis requiring further validation through clinical and mechanistic studies.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the BIBLIO reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0302/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0302/prf

Funding: This study was supported by the Government-funded Program for Cultivating Outstanding Talents in Clinical Medicine (No. 361007) and the Hebei Provincial Medical Science Research Project Plan (No. 20231510).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0302/coif). All authors report that this study was supported by the Government-funded Program for Cultivating Outstanding Talents in Clinical Medicine (No. 361007) and the Hebei Provincial Medical Science Research Project Plan (No. 20231510). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Henriques M, Cilio S, Ramos P, et al. A Systematic Review on Administration of Botulinum Toxin in the Management of Male Sexual Dysfunctions. Andrology 2025; Epub ahead of print. [Crossref]
2. Shamloul R, Ghanem H. Erectile dysfunction. Lancet 2013;381:153-65. [Crossref] [PubMed]
3. Hatzimouratidis K, Amar E, Eardley I, et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol 2010;57:804-14. [Crossref] [PubMed]
4. Rowland DL, Oosterhouse LB, Kneusel JA, et al. Comorbidities Among Sexual Problems in Men: Results From an Internet Convenience Sample. Sex Med 2021;9:100416. [Crossref] [PubMed]
5. Xie Z, Lu J, Zhang X, et al. Efficacy of Chinese herbal medicine in the treatment of anxiety and depression in male sexual dysfunction: a systematic review and meta-analysis. Sex Med 2025;13:qfaf048. [Crossref] [PubMed]
6. Przydacz M, Chlosta M, Rajwa P, et al. Population-level prevalence, effect on quality of life, and treatment behavior for erectile dysfunction and premature ejaculation in Poland. Sci Rep 2023;13:13168. [Crossref] [PubMed]
7. Salonia A, Bettocchi C, Boeri L, et al. European Association of Urology Guidelines on Sexual and Reproductive Health-2021 Update: Male Sexual Dysfunction. Eur Urol 2021;80:333-57. [Crossref] [PubMed]
8. Zaki SM, Zahra MA, Alshobaki S, et al. Prevalence and Determinants of Sexual Dysfunction in Male Diabetic Patients in Saudi Arabia: A Cross-Sectional Study. Cureus 2025;17:e82901. [Crossref] [PubMed]
9. Sultan MI, Ibrahim SA, Youssef RF. Impact of a Mediterranean diet on prevention and management of urologic diseases. BMC Urol 2024;24:48. [Crossref] [PubMed]
10. Scanavino MT, Mori E, Nisida VV, et al. Sexual Dysfunctions Among People Living With HIV With Long-Term Treatment With Antiretroviral Therapy. Sex Med 2022;10:100542. [Crossref] [PubMed]
11. Saleh R, Majzoub A, Abu El-Hamd M. An update on the treatment of premature ejaculation: A systematic review. Arab J Urol 2021;19:281-302. [Crossref] [PubMed]
12. Zhuravleva ZD, Johansson A, Jern P. Erectile Dysfunction in Young Men: Testosterone, Androgenic Polymorphisms, and Comorbidity With Premature Ejaculation Symptoms. J Sex Med 2021;18:265-74. [Crossref] [PubMed]
13. Huang AC, Liu MC, Tsai TH, et al. Low-frequency electroacupuncture at acupoints guanyuan (CV4) and zhongji (CV3) lengthen ejaculatory latency and improves sexual behavior in male rats. Chin J Physiol 2020;63:163-70. [Crossref] [PubMed]
14. Eserdag S, Kurban D, Yakut E, et al. Insights Into the Vaginismus Treatment by Cognitive Behavioral Therapies: Correlation With Sexual Dysfunction Identified in Male Spouses of the Patients. J Family Reprod Health 2021;15:61-9. [Crossref] [PubMed]
15. Krishnappa P, Tammaro S, Sneha J, et al. Virtual reality in the management of male sexual dysfunction: an updated narrative review of the literature. Sex Med Rev 2026;14:qeaf051. [Crossref] [PubMed]
16. Sahin E, Brand A, Cetindag EN, et al. Pelvic physical therapy for male sexual disorders: a narrative review. Int J Impot Res 2025;37:941-9. [Crossref] [PubMed]
17. Yaacov D, Nelinger G, Kalichman L. The Effect of Pelvic Floor Rehabilitation on Males with Sexual Dysfunction: A Narrative Review. Sex Med Rev 2022;10:162-7. [Crossref] [PubMed]
18. Meng F, Liao X, Chen H, et al. Bibliometric and visualization analysis of literature relating to diabetic erectile dysfunction. Front Endocrinol (Lausanne) 2022;13:1091999. [Crossref] [PubMed]
19. Basharpoor S, Naeim M, Narimani M. Compulsivity and impulse control in behavioral addictions: A bibliometric and conceptual analysis of global research trends, thematic gaps, and future directions. Psychol Addict Behav 2026;40:460-8. [Crossref] [PubMed]
20. Al Shubbar MD, Alhojailan RA, Alzahrani SA, et al. Global Research Trends and Hotspots in Cardiac Devices: A Bibliometric and Visual Analysis. Healthcare (Basel) 2025;13:3144. [Crossref] [PubMed]
21. Huang X, Jin J, Li Y, et al. Clinical treatment, research topic and global trends of Kaposiform hemangioendothelioma: a review and bibliometric analysis. Int J Surg 2025; Epub ahead of print. [Crossref]
22. He H, Liu C, Chen M, et al. Effect of Dietary Patterns on Inflammatory Bowel Disease: A Machine Learning Bibliometric and Visualization Analysis. Nutrients 2023;15:3442. [Crossref] [PubMed]
23. Chen S, Di J, Zhang Z, et al. Current Applications and Future Challenges of Mesenchymal Stem Cell-Extracellular Vesicles in Tissue Engineering: A Bibliometric Analysis. Int J Nanomedicine 2025;20:14885-910. [Crossref] [PubMed]
24. Pryor JL, Althof SE, Steidle C, et al. Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials. Lancet 2006;368:929-37. [Crossref] [PubMed]
25. Canguven O, Khalafalla K, Al Ansari A. Low-intensity extracorporeal shockwave therapy for erectile dysfunction. Arab J Urol 2021;19:340-5. [Crossref] [PubMed]
26. Liu MC, Chang ML, Wang YC, et al. Revisiting the Regenerative Therapeutic Advances Towards Erectile Dysfunction. Cells 2020;9:1250. [Crossref] [PubMed]
27. Lewis RW, Fugl-Meyer KS, Corona G, et al. Definitions/epidemiology/risk factors for sexual dysfunction. J Sex Med 2010;7:1598-607. [Crossref] [PubMed]
28. Laumann EO, Nicolosi A, Glasser DB, et al. Sexual problems among women and men aged 40-80 y: prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviors. Int J Impot Res 2005;17:39-57. [Crossref] [PubMed]
29. McMahon CG, Althof SE, Waldinger MD, et al. An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine (ISSM) ad hoc committee for the definition of premature ejaculation. J Sex Med 2008;5:1590-606. [Crossref] [PubMed]
30. Serefoglu EC, McMahon CG, Waldinger MD, et al. An evidence-based unified definition of lifelong and acquired premature ejaculation: report of the second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation. J Sex Med 2014;11:1423-41. [Crossref] [PubMed]
31. Althof SE, McMahon CG, Waldinger MD, et al. An Update of the International Society of Sexual Medicine’s Guidelines for the Diagnosis and Treatment of Premature Ejaculation (PE). Sex Med 2014;2:60-90. [Crossref] [PubMed]
32. Doggrell SA. Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction. Expert Opin Pharmacother 2005;6:75-84. [Crossref] [PubMed]
33. Moreland AJ, Makela EH. Selective serotonin-reuptake inhibitors in the treatment of premature ejaculation. Ann Pharmacother 2005;39:1296-301. [Crossref] [PubMed]
34. Montorsi F, Adaikan G, Becher E, et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med 2010;7:3572-88. [Crossref] [PubMed]
35. McMahon CG. Priapism associated with concurrent use of phosphodiesterase inhibitor drugs and intracavernous injection therapy. Int J Impot Res 2003;15:383-4. [Crossref] [PubMed]
36. McMahon CG, Giuliano F, Dean J, et al. Efficacy and safety of dapoxetine in men with premature ejaculation and concomitant erectile dysfunction treated with a phosphodiesterase type 5 inhibitor: randomized, placebo-controlled, phase III study. J Sex Med 2013;10:2312-25. [Crossref] [PubMed]
37. Elbardisi H, Majzoub A, Daniel C, et al. Endocrine contribution to the sexual dysfunction in patients with advanced chronic kidney disease and the role of hyperprolactinemia. Andrologia 2021;53:e14135. [Crossref] [PubMed]
38. Fan D, Mao W, Wang G, et al. Study on the relationship between sex hormone changes and erectile dysfunction in patients with chronic prostatitis/chronic pelvic pain syndrome. Ann Palliat Med 2021;10:1739-47. [Crossref] [PubMed]
39. Zhou Z, Wang Y, Chai Y, et al. The efficacy of platelet-rich plasma (PRP) alone or in combination with low intensity shock wave therapy (Li-SWT) in treating erectile dysfunction: a systematic review and meta-analysis of seven randomized controlled trials. Aging Male 2025;28:2472786. [Crossref] [PubMed]
40. Wang C, Zhang H, Liu Z, et al. A Modified Procedure to Diagnose Erectile Dysfunction Using the International Index of Erectile Function (IIEF-6) Combined With the Premature Ejaculation Diagnosis Tool (PEDT) via an Internet Survey. Sex Med 2022;10:100506. [Crossref] [PubMed]
41. Clark H, Venishetty N, Howell S, et al. Utilization of artificial intelligence in Men’s Health: Opportunities for innovation and quality improvement. Int J Impot Res 2026;38:381-92. [Crossref] [PubMed]
42. Giuliano F, Clément P. Physiology of ejaculation: emphasis on serotonergic control. Eur Urol 2005;48:408-17. [Crossref] [PubMed]
43. Qiu J, Wang B, You X, et al. Neurobiology of premature ejaculation: Serotonergic mechanisms and emerging therapeutic insights. Andrologia 2025; [Crossref]
44. Angulo J, Gonzalez-Corrochano R, Cuevas P, et al. Combination of nebivolol and sildenafil reverses erectile dysfunction in diabetic rats through enhancement of the NO/cGMP pathway. Diabetes 2009;58:A86.
45. Marson L, Platt KB, McKenna KE. Central nervous system innervation of the penis as revealed by the transneuronal transport of pseudorabies virus. Neuroscience 1993;55:263-80. [Crossref] [PubMed]