Trends in psychogenic erectile dysfunction research: a bibliometric and visualized study

2.1 Literature search strategy

A literature search was performed using the PubMed and Web of Science databases and the subject term “psychogenic erectile dysfunction”, as shown in Table 1. The search timeframe was limited to January 2000 to December 2022, and the literature identified were evaluated for subsequent analysis.

2.2 Data download

The raw data were downloaded from PubMed or Web of Science and then summarized using Endnote, recording both complete records and cited references.

2.3 Visual analysis of the literature

We extracted a range of key information from the identified literature in the Endnote database (version X9, Clarivate Analytics), including the number of publications per year, country or region, journal name and keywords. Origin (2022, OriginLab, Northampton, MA, USA) and VOSviewer software (1.6.16, Leiden University, Leiden, The Netherlands) were utilized for visual analysis.

3.1 Overview of the literature

A total of 118 papers relating to pED were retrieved from the two databases. These papers consisted of 91 clinical studies, 16 systematic reviews, five animal studies, four case reports and two trial protocols. Of the pED clinical studies, 28 articles focused on mechanistic studies, 25 articles focused on treatment, and 18 articles focused on diagnosis. Although the research on pED is becoming more in-depth, there is still a need to increase the overall number of publications, as depicted in Fig. 1A.

3.2 Country/region analysis

When analyzing the 118 publications, we identified authors from 25 different countries and regions. Of these, Chinese scholars had the highest number of publications with 47, followed by Italy, the United States, Japan, Germany, Spain, India, Turkey, Canada and Pakistan (as shown in Fig. 1B). Although collaborative relationships were evident among these countries, there is still potential for further strengthening these connections, as shown in Fig. 1C.

3.3 Journal analysis

The 118 papers were published in a total of 62 journals. Fig. 1D shows the top eight journals, with the International Journal of Impotence Research producing the highest number of published papers. This was followed by the Journal of Sexual Medicine, Andrology, Andrologia, Sexual Medicine, Urology and PLOS ONE. This suggested that pED, a common male disorder, is predominantly published in the fields of male medicine and sexual medicine.

Fig. 1.Published literature relating to pED. (A) type of literature study and the number accounting for the 118 publications; (B) the number of papers by country; (C) the cooperative relationships between country or region; (D) the number of publications by the journals.

3.4 Literature citation analysis

Table 2 presents the top 10 pED-related publications based on citation frequency. The literature mainly focused on clinical studies, with the most cited research areas relating to the treatment of pED by oral phosphodiesterase type 5 inhibitor (PDE5I), cognitive behavioral guidance, and the investigation of pathological mechanisms. Of these, brain activity studies were the most frequent. Rosen et al. [10] conducted a systematic review of treatment approaches for pED, including cognitive-behavioral interventions, sexual education and guidance, and couple and psychological counseling. These authors also combined these approaches with oral PDE5I treatment to gain a better understanding of the disease in terms of classification and treatment. Their study was cited 103 times and provided significance guidance for future research on pED.

3.5 Keyword analysis

In this study, we used VOSviewer to create a co-occurrence network of keywords in the research area. The co-occurrence network was divided into different clusters based on time nodes, with each cluster represented by a different color. This visualization revealed that earlier research hotspots were primarily centered around the treatment of pED. This included the use of apomorphine, PDE5I, sexual behavior guidance and psychological interventions. As our understanding of this condition deepened, the treatment objectives for pED have shifted towards improving the sexual satisfaction of both men and their partners. In terms of diagnosis, keywords, such as nocturnal penile tumescence and rigidity (NPTR) and color doppler duplex ultrasonography (CDDU) showed that certain tests can be used to diagnose pED. In recent years, a range of other keywords have been associated with pED, including magnetic resonance imaging (MRI), network, neural pathway, functional connectivity and brain mapping. Furthermore, in conjunction with the keywords shown in Fig. 2, research relating to the neurophysiology of the brain in pED patients has grown notably since 2015. This suggests that there may be abnormalities in brain activity, particularly in terms of cortical structure or function. Based on the keywords shown in Fig. 2, we considered that pED research is primarily focused on three areas: mechanisms, diagnosis and treatment.

Fig. 2.Keyword co-occurrence analysis. The nodes represent keywords. The size of the dots represent the number of keywords. Different node colors represent different times.

4.1 Patients with pED may have abnormalities of the central nervous system

Table 3 summarizes relevant studies on pED that were published over the last decade, including patient sample size, age, international index of erectile function-5 (IIEF-5) (or IIEF), examination modality and study conclusions. By identifying the central neural mechanisms involved in pED, this table provides a comprehensive overview of the abnormal regions and neurological representations found in various brain regions, as depicted in Fig. 4A. Patients with pED exhibit structural brain damage, which is evident from the reduced levels of white and gray matter. Furthermore, pED patients demonstrate dysfunction in multiple brain regions that are primarily characterized by reduced connectivity and abnormal activity. Upon dividing the summary results of Fig. 4A into regions (as shown in Fig. 4B), we found that these abnormalities were mainly concentrated in the limbic system and frontal lobes.

Fig. 4.Diagram depicting brain structure and dysfunction in patients with pED. (A) brain structure and dysfunction (based on the conclusions in Table 3, the abnormal brain regions were collated and attributed to abnormalities in the white matter, grey matter, function and connectivity of the brain. In the classification of white matter, grey matter, connectivity and activity, the color of the rectangles used for the abnormal brain areas corresponds to the color of the rectangles used for related references); (B) distribution of brain structure and dysfunction (17, 15, 10, 5 and 3 represent the frequency of occurrence in related regions in Fig. 4A, respectively). Abbreviations: L, left; R, right; ACC, anterior cingulate cortex; aINS, anterior insula; AMYG, amygdala; ANG, angular gyrus; CC, corpus callosum; CE, cerebellum; CG, cingulate gyrus; CR, corona radiata; CST, corticospinal tract; dlPFC, dorsolateral prefrontal cortex; EC, external capsule; FFG, fusiform gyrus; GP, globus pallidus; HPO, hypothalamus; IC, internal capsule; IFG, inferior frontal gyrus; INS, insula; ITC, inferotemporal cortical; ITG, inferior temporal gyrus; MCC, middle cingulate cortex; mPFC, medial prefrontal cortical; NAcc, nucleus accumbens; OFC, orbitofrontal cortex; PCC, posterior cingulate cortex; PCUN, precuneus; PFC, prefrontal cortex; PHG, parahippocampal gyrus; PreCG, precentral gyrus; PoCG, postcentral gyrus; SFG, superior frontal gyrus; SLF, superior longitudinal fasciculus; SMG, supramarginal gyrus; TPJ, temporoparietal junction.

4.2 The diagnosis of pED often involves three different modalities, each with its own clinical application

Distinguishing between pED and organic ED requires a comprehensive evaluation for patients on first presentation. This evaluation involves taking a medical and sexual history, conducting a physical examination and laboratory tests. It remains challenging to differentiate the type of ED using IIEF-5 alone [75]. Therefore, clinicians often choose a combination of treatments, such as oral PDE5I with audiovisual sexual stimulation (AVSS), intra-cavernosal injection (ICI) with CDDU and NPTR testing.

The NPTR test is a non-invasive method that effectively distinguishes between organic and pED. This test is considered the primary modality for differentiating pED from organic ED, which is often misdiagnosed as pED in individuals with normal NPTR [21]. However, there may be situational factors during the examination that can cause patient discomfort and tension during wear, potentially affecting the accuracy of the results [76]. Therefore, it may be necessary to gather data over consecutive nights to confirm the diagnosis [77]. Both sexually stimulated erections and those occurring during sleep involve the same vascular and penile structures, but they are regulated by different neural mechanisms. The mechanisms responsible for initiating and maintaining sleep-related erections remain unclear [78, 79]. In addition, Hatzichristou et al. [80] found that erectile events lasting at least 10 minutes and occurring in up to 60% of the head of the penis could be considered abnormal according to the parameters of a normal NPTR test. However, this study only evaluated 12 men aged 21–24 years and therefore suffers from certain limitations, including the small sample size and the small age distribution. In contrast, Liu et al. [21] established the diagnostic parameters for this test as normal by referencing previous studies [81, 82]. These parameters include at least 70% of the head and base, an increase in swelling of at least 2 cm in the head and 3 cm in the base, and an event lasting not less than 10 minutes [14]. However, there is still no commonly accepted gold standard for the normal parameter values of the NPTR test.

ICI testing is often combined with CDDU [80, 83, 84]. The ICI + CDDU is highly correlated with NPTR with regards to diagnosing pED and is preferred in cases of ED involving vascular lesions [85]. Some studies suggest that there may be a delayed response after ICI for pED, and that sufficient sexual stimulation is necessary to improve erectile hardness. Re-dosing may be an option for those who do not achieve an erection after leaving the hospital [86, 87]. Santi et al. [88] proposed a two-step approach to identify pED. The first step involves the evaluation of medical history and hormone levels. Subsequently, an intra-penile injection of 5 µg of prostaglandin E-1 (PGE-1) is administered. If a full pharmacological erection is not achieved, a CDDU evaluation is performed after administering another 10 µg of PGE-1 to measure intra-penile blood flow and diagnose pED. This approach has a sensitivity of 97% and a specificity of 100% and therefore helps to avoid further unnecessary retesting [88]. The accuracy of ICI + CDDU as an invasive test may be influenced by psychological and environmental factors, leading to false negatives. In addition, its accuracy is controversial, particularly with regards to the determination of venous abnormalities based on reduced systolic maximum flow rate combined with abnormal diastolic minimum flow rate [89, 90].

According to research, the AVSS, based on RigiScan, is a relatively simple, economical and less time-consuming method that closely mimics erection during normal intercourse and is not affected by sleep [91]. However, Mizuno et al. [92] found that the AVSS is associated with a high false negative rate, with a sensitivity of 71% and a specificity of 92%. To further evaluate the accuracy of AVSS in identifying pED, Wang et al. [93] conducted a study featuring 1169 ED patients. These authors found that when the AVSS was combined with PDE5I and RigiScan tests, the sensitivity and specificity were 87.7% and 93.4%, respectively, when differentiating between psychogenic and organic ED [93]. Combining oral PDE5I with AVSS can help to mitigate the influence of vascular factors when diagnosing patients with pED. This approach offers higher levels of accuracy and can confirm the diagnosis of normal sexual desire and erectile function, even in patients with normal AVSS test results. However, factors such as the level of sexual desire, environmental and psychological factors during the examination, and the potential of adverse effects arising from a single high dose of PDE5I, can still influence the results [94]. Some researchers have attempted to minimize the influence of environmental factors by utilizing techniques such as three-dimensional head-mounted displays [95]. Data arising from AVSS testing studies is limited and may be subject to bias. Moreover, there is a lack of standardized reference values for men in different countries. Nevertheless, considering the standards set by the European Association of Urology, AVSS may be more suitable as a primary screening tool.

4.3 Treatment options for pED often involve multiple therapeutic modalities

Patients with pED can be administered with a range of treatment options, including psychosexual therapy, oral medications, ICI and traditional Chinese medicine. Although 32.3% of ED patients experience an improvement in erectile symptoms after receiving a definitive pED diagnosis, many still seek treatment [96]. PDE5I, known for its convenient oral administration, effective therapeutic results, and good safety profile, has become widely accepted and is recommended as a first-line treatment for pED by multiple guidelines [97, 98, 99]. In a study involving 141 ED patients, 23% were diagnosed as having pED; of these patients, 87% benefited from sildenafil treatment [100]. However, another study reported a high failure rate of 30–40% when treated with PDE5I [101]. The reasons for failure may have included inadequate sexual stimulation, incorrect dosing and the inappropriate timing of intercourse. In a study conducted by Li et al. [102], 90 patients with pED were randomly assigned to either a tadalafil step-down group or a tadalafil 5 mg group. The tadalafil step-down group received a dosage of 20 mg/day for the first month, 10 mg/day for the second month, and 5 mg/day for the third month. The results showed a more significant improvement in IIEF-5 and erectile hardness score in the tadalafil step-down group when compared to the tadalafil 5 mg group [102]. Similarly, Huang et al. [103] conducted another study using a step-down treatment regimen with tapered discontinuation of the drug. Patients were administered a daily dose of tadalafil (5 mg) in the first month; this resulted in high efficacy and increased self-confidence in their successful sexual experiences. In the second month, the treatment continued with 5 mg of tadalafil every other day; this maintained good efficacy and achieved a cure rate of 85.71% [103]. While PDE5I can restore erectile confidence in patients with pED, the temporary use of ICI in patients who did not respond to PDE5I can also lead to immediate erection [104, 105]. Lidawi et al. [106] demonstrated the effectiveness of a short course of ICI therapy involving 1 to 2 self-injections. Most patients used 0.5 mL of the therapy, combined with opium poppy alkaloids (6 mg) and 6 mg of prostaglandin Dil. This treatment effectively addressed psychological barriers related to sexual performance anxiety but did not result in abnormal erections. Pharmacotherapy for pED may not be accepted by some patients due to cultural and other reasons, as they believe this strategy only provides a temporary solution to the problem. In countries such as China, acupuncture is a common alternative for treating pED. While it may not result in immediate erection, acupuncture can improve IIEF-5 scores and overall sexual satisfaction. In addition, acupuncture can also alleviate symptoms such as anxiety, depression and insomnia, which are often experienced by pED patients. As a multi-targeted non-pharmacological therapy, acupuncture can be considered a viable option for the treatment of pED [107].

pED is often attributed to a range of factors including anxiety, depression, a lack of sexual education, sexual trauma, relationship issues and previous unsuccessful sexual experiences [3, 6, 7]. In cases where treatment with PDE5I is ineffective, patients may turn to psychotherapy. However, in clinical practice, pED patients may deny the presence of psychological factors, making it challenging to obtain the patient’s cooperation for psychosexual therapy alone [103]. Some studies suggest that the efficacy of psychotherapy alone is comparable to that of psychotherapy when combined with PDE5I [15]. Recently, a protocol that combines cognitive-behavioral sex therapy (CBST) with oral PDE5I has been adopted in some clinical settings [11, 108]. This protocol integrates traditional sex therapy with modern cognitive-behavioral therapy. CBST includes psychosexual education, sexual role-playing exercises, cognitive reframing of attitudes related to sexual behavior, Socratic dialogue towards sexual activity, and the development of sexual communication skills [11, 109, 110]. Previous studies have shown that patients with pED can benefit from CBST and the combination with sildenafil [108]. This combination of CBST and PDE5I may be effective in helping couples to improve their relationships and reduce the psychological distress associated with pED. This treatment approach focuses on the couple as a whole rather than solely addressing the individual symptoms of sexual dysfunction in males [111]. This highlights the importance of considering the role of the sexual partner [112]. Therefore, pED may not be solely caused by organic factors, and the treatment of pED aims to boost the patient’s self-confidence and address the psychological factors that contribute to sexual intercourse difficulties by applying various therapies [113]. This approach differs from the treatment of organic ED and aligns with the European Association of Urology guidelines on ED treatment, which emphasize a holistic approach to curing the patient’s symptoms [1].