Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance [1]. This prevalent medical condition has serious implications for quality of life [2]. ED is a complex medical issue with several known causes, including vascular, hormonal, neurologic and psychological dysfunctions, and is associated with chronic health conditions [3]. An association with numerous risk factors including age, diabetes mellitus, dyslipidaemia, hypertension, CVD, obesity, MetS, hyperhomocysteinemia, lack of exercise, smoking and drug use has been reported [4].

ED is classified into three main categories:

ED precedes systemic manifestations of vascular disease. Since it is strongly linked with endothelial dysfunction, it may indicate a higher risk of cardiovascular problems and other health conditions [10][11].

The overall prevalence of ED in the MALES sample was 16%. ED prevalence varied markedly by country, however, from a high of 22%of men in the US reporting ED to a low of 10% in Spain. The prevalence of self-reported ED increased with increasing age [12]. According to Goldstein et al., overall ED prevalence ranged from 37.2% (Brazil) to 48.6% (Italy) [13]. It is estimated that in 1995 there were over 152 million men worldwide who experienced ED; the projections for 2025 show a prevalence of approximately 322 million with ED, an increase of nearly 170 million men. [14].

ED affects not only physical health but also mental well-being and relationships. Many men with ED experience low self-esteem, depression, and anxiety, which can further worsen the condition [15 ‒ 17]. The psychological impact is not limited to patients with ED since it also involves their partners. They can feel guilty, unwanted, or not attractive anymore. Shame and worrisome can happen leading to the partners being distant from each other. Eventually, the crisis in the relationship would be the result [18].

The economic impact of ED is significant, as the demand for treatments such as phosphodiesterase type 5 (PDE5) inhibitors, vacuum devices, low-intensity shock wave therapy and regenerative therapies continues to grow [19 ‒ 22]. The median help-seeking interval was 24.5 months, with embarrassment (33%) and the perception of ED as a normal aging process (26.7%) identified as the primary barriers to timely consultation. These findings highlight the urgent need for affordable healthcare services and widespread public education to promote early diagnosis and management of ED [23].

This review aims to provide an overview of ED by focusing on the following areas:

This review aims to present current evidence and highlight research gaps, providing useful insights for healthcare providers, researchers, and policymakers. The goal is to improve the understanding and treatment of ED to enhance men’s health and well-being.

This study employed a systematic literature review (SLR) approach to synthesize existing evidence on the diagnosis, management, and emerging interventions for ED. The SLR methodology was chosen to ensure a comprehensive and unbiased evaluation of peer-reviewed studies, clinical trials, and reviews.

The review was guided by the following research questions:

These questions were designed to address gaps in knowledge and provide actionable insights into ED management [24].

A structured and systematic search strategy was implemented to identify relevant studies across multiple databases. Databases searched included PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar.

The search involved using keywords combined with Boolean operators to ensure comprehensive coverage of relevant literature. Examples of search terms and combinations included “Erectile dysfunction AND diagnosis,” “Psychogenic ED AND psychological assessment,” “PDE5 inhibitors AND efficacy AND safety,” “Vacuum erection devices OR penile implants,” and “Emerging therapies AND erectile dysfunction.”

Studies selected for review included peer-reviewed articles published in English, specifically addressing diagnosis, treatment, or emerging interventions for ED. The literature search was limited to articles published between 2000 and 2025 to ensure relevance to contemporary clinical practices. Excluded from the review were non-peer-reviewed sources such as blogs and opinion pieces, studies that did not focus explicitly on ED (for example, general sexual health topics without a specific emphasis on ED), and articles that were either unavailable in full text or lacked sufficient data for meaningful analysis.

The selection process of studies followed the PRISMA framework, encompassing the four main stages of identification, screening, eligibility assessment, and final inclusion [25]. Initial database searches identified 951 articles. Titles and abstracts of these studies were then screened to remove 387 duplicates and irrelevant studies. Subsequently, the remaining full-text articles were assessed thoroughly based on the predefined inclusion and exclusion criteria. After this evaluation, 24 studies met the criteria and were included in the final review. The entire selection process was visually documented using a PRISMA flow diagram (Fig. 1) [18].

Data extraction was conducted using a standardized template to ensure consistency across all included studies. The extracted information covered essential study characteristics, including authors and year of publication, study design (such as randomized controlled trials, cohort studies, or systematic reviews), and details of the study population, including age and comorbidities. Additionally, interventions or diagnostic tools evaluated, outcomes measured (for example, efficacy, safety, and patient satisfaction), and any identified limitations or biases were systematically documented.

The quality of included studies was systematically assessed using established and validated assessment tools. For randomized controlled trials (RCTs), the Cochrane Risk of Bias Tool was employed [24]. Observational studies were evaluated using the Newcastle-Ottawa Scale (NOS) [26]. Systematic reviews included in the study were assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) [27]. Based on these assessments, studies were categorized into high, moderate, or low quality according to predefined criteria.

The synthesis of data involved both qualitative and quantitative approaches. Qualitative synthesis consisted of narrative analysis, which helped identify themes and patterns, particularly among studies focused on diagnostic methods and psychological assessments. Quantitative synthesis included meta-analysis, where feasible, to statistically compare treatment outcomes, such as the efficacy rates of PDE5 inhibitors. Statistical heterogeneity was measured using I² statistics. When quantitative pooling of data was not possible due to methodological differences or study characteristics, findings were summarized narratively, following the SWiM (Synthesis Without Meta-analysis) guidelines [28].

Since the current study involved reviewing publicly available literature, formal ethical approval was not required. Nevertheless, careful citation and attribution of sources were performed throughout to maintain academic integrity and avoid plagiarism.

The diagnosis of ED involves identifying underlying psychological, physiological, or mixed causes and evaluating the severity of the condition. A comprehensive diagnostic approach allows clinicians to accurately differentiate between psychogenic and organic ED, facilitating tailored treatment strategies. Typically, the diagnostic process incorporates patient history, physical examination, laboratory tests, and specialized diagnostic tools.

Patient history remains foundational in diagnosing ED, providing essential details about symptom onset, duration, and characteristics. Clinicians frequently use validated questionnaires to quantify ED severity and assess the impact on quality of life. The International Index of Erectile Function (IIEF) is widely considered the gold standard for evaluating ED severity, assessing domains such as erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction [29]. While the IIEF is effective, its reliance on patient self-reporting introduces potential biases, including recall bias or social desirability. A shorter screening tool, the Sexual Health Inventory for Men (SHIM), offers rapid assessment but lacks the comprehensive nature of the IIEF [30]. The IIEF requires more research on structural validity (IIEF-15), internal consistency (IIEF-15 and IIEF-5), construct validity (IIEF-15), measurement error (IIEF-15 and IIEF-5), and responsiveness (IIEF-5). The most pressing matter for future research is determining the unidimensionality of the IIEF-5 and the exact factor structure of the IIEF-15 [31]. The Erection Hardness Score (EHS), evaluating erection firmness on a simplified scale, is intuitive and straightforward, though less detailed compared to other measures [32].

A thorough physical examination aids in diagnosing ED by identifying anatomical abnormalities, hormonal imbalances, or signs of systemic diseases. Critical components include evaluation of secondary sexual characteristics, such as body hair distribution and muscle mass; examination of penile and testicular anatomy; assessment for hormonal irregularities; and signs indicative of cardiovascular or neurological disorders. Although physical examination provides valuable information about potential organic causes of ED, it does not conclusively differentiate psychogenic ED from organic types, necessitating further assessment [33].

Laboratory tests are essential for identifying systemic conditions that may underlie ED, such as diabetes, cardiovascular diseases, or hormonal disorders. Hormonal assays, including testosterone, prolactin, thyroid-stimulating hormone (TSH), and luteinizing hormone (LH), help assess endocrine function and identify hormonal imbalances such as hypogonadism [34]. A metabolic panel evaluating glucose levels, lipid profiles, and liver or kidney function can detect metabolic contributors to ED such as diabetes or dyslipidemia. Though physical examination and laboratory evaluation of most men with ED may not reveal the exact diagnosis, these opportunities to identify critical comorbid conditions should not be missed [32].

When initial evaluations fail to clearly identify the cause of ED, specialized diagnostic techniques may provide more precise insights into physiological mechanisms. Nocturnal Penile Tumescence (NPT) testing, which measures nighttime erections using devices like strain gauges or snap-gauge bands, is highly accurate for differentiating psychogenic from organic ED; normal nocturnal erections typically suggest a psychogenic origin, while absent or reduced erections indicate organic causes [35]. Penile Doppler ultrasound is a non-invasive imaging technique considered the gold standard for diagnosing vascular ED, assessing penile blood flow, and detecting arterial insufficiency or venous leakage. Despite its diagnostic effectiveness, penile Doppler ultrasound requires specialized equipment and clinical expertise [36]. Dynamic Infusion Cavernosometry and Cavernosography (DICC) assesses venous leakage through saline infusion into the corpora cavernosa, measuring intracavernosal pressure. However, its invasiveness and complexity limit its use primarily to research contexts [37].

Despite advances in diagnostic tools, several significant challenges persist. Differentiating psychogenic from organic ED remains challenging due to overlapping symptoms; combining NPT testing with psychological assessments can improve diagnostic accuracy [38]. Additionally, societal stigma and embarrassment frequently lead to underreporting of symptoms, delaying accurate diagnosis and timely treatment [15]. Limited access to advanced diagnostic technologies such as penile Doppler ultrasound and DICC, especially in low-resource settings, restricts comprehensive diagnostic capability [35][36]. Specific diagnostic tests could help discern between vasculogenic, hormonal or psychogenic causes of ED. [4].

In summary, diagnosing ED relies on a carefully integrated approach combining patient history, through physical examination, targeted laboratory assessments, and specialized diagnostic techniques. Although standardized tools such as the IIEF questionnaire and penile Doppler ultrasound significantly enhance diagnostic precision, overcoming persistent barriers such as stigma, limited access to advanced diagnostic methods, and overlapping symptom profiles remains essential. Addressing these challenges requires holistic clinical practice emphasizing patient-centered care and interdisciplinary expertise.

The management of ED includes a wide range of interventions, from pharmacological therapies to non-pharmacological options, each tailored to the underlying cause and severity of the condition. Effective management strategies not only restore sexual function but also significantly improve psychological well-being and overall quality of life. A systematic review has shown a consistent discontinuation rate for all available ED treatment options [39].

Pharmacological therapies constitute the cornerstone of ED management, with oral medications typically serving as first-line treatments. Phosphodiesterase Type 5 (PDE5) inhibitors are the most widely prescribed pharmacological option. PDE5 inhibitors function by enhancing nitric oxide activity, which relaxes penile smooth muscle and increases blood flow during sexual stimulation [19].

Among PDE5 inhibitors, sildenafil is generally well-tolerated, although common side effects include headaches, facial flushing, and nasal congestion. Patient satisfaction with sildenafil is typically high, attributed to its ease of use and rapid onset of action (around 30 – 60 minutes). The percentage of men reporting improved erections on the global assessment question was statistically significantly higher with sildenafil vs placebo for all age subgroups; the percentage with sildenafil tended to decrease with increasing age (< 65 years, 80%; 65 ‒ 74 years, 69%; ≥ 75 years, 59%) [40]. Tadalafil, another PDE5 inhibitor, has efficacy comparable to sildenafil but provides an extended duration of action lasting up to 36 hours, allowing greater spontaneity. It also carries fewer dietary restrictions, contributing to its popularity among patients. Tadalafil daily provides a preferable therapeutic effect for ED with a lower incidence of treatment-emergent side effects relative to tadalafil on-demand after at least 24 weeks of long-term treatment [41]. Vardenafil exhibits similar efficacy to sildenafil and tadalafil and is particularly effective in diabetic patients, though data on its long-term use are relatively limited, affecting patient satisfaction levels [42]. Vardenafil is a highly efficacious and well tolerated PDE5 inhibitor that demonstrated non-inferiority to other PDE5 inhibitors as well as a favorable safety profile in men with underlying cardiovascular and metabolic conditions [43].

Intracavernosal injections, such as alprostadil, represent another pharmacological treatment option for patients who do not respond to PDE5 inhibitors. These injections directly induce erections and have a high success rate. Despite their efficacy, injections pose risks of penile pain, priapism, and potential scarring, resulting in comparatively lower patient satisfaction due to invasiveness and discomfort. Since intracavernous injection therapy was more efficacious, better tolerated, and preferred by the patients and their partners, it should be offered as the first-choice treatment if oral therapy fails or is contraindicated [44]. Topical treatments, including alprostadil creams or gels applied to the penis or urethra, offer moderate efficacy with minimal systemic side effects, though patient feedback varies due to inconsistent results [45].

Non-pharmacological therapies complement or offer alternatives to pharmacological treatments, especially for men unable or unwilling to tolerate medications. Vacuum erection devices (VEDs), as one of the widely used approved therapies, mechanically draw blood into the penis using negative pressure, maintaining erections through constriction bands. VED could be a good alternative therapy for patients who denied peroral therapy [20][46].

Penile implants — either inflatable or malleable — are surgically implanted devices providing a permanent solution for refractory ED, achieving near 100% efficacy in producing erections [47][48]. However, surgical risks such as infection, mechanical malfunction, or scarring remain concerns [59 ‒ 51]. Nevertheless, 97% of patients affirmed to use penile prostheses frequently. 69% of patients and 90% their partners affirmed that they never had problems with the use of the prosthesis and they considered themselves satisfied. 79% of patients answered that this therapeutic method has led to evident improvements in their sexual life. 79% of patients gave a score equal or major than seven and 82% of their partners gave a score equal or major than seven. 97% of patient reported they would suggest this treatment to other people [52].

Psychotherapy, particularly cognitive-behavioral therapy (CBT), effectively addresses psychogenic ED by targeting underlying anxiety, relationship difficulties, and stress. Psychological interventions on ED are based on existing theoretical models that are grounded in empirical evidence [38]. Although it is generally ineffective for purely organic ED, psychotherapy carries no physical risks, only requiring patient commitment and time. Lifestyle modifications, such as weight reduction, increased physical activity, dietary improvements, and smoking cessation, have proven beneficial in men with comorbidities like obesity or hypertension [53]. Overall, several studies have shown that lifestyle modifications, including physical activity (particularly aerobic exercise), weight loss (including bariatric surgery), and treatment of CVD risk factors, may improve sexual function in men with ED [54].

Despite significant advancements in ED management, several ongoing challenges continue to limit optimal patient outcomes. One major barrier involves differentiating treatment efficacy due to individual variability, as responses differ widely depending on age, comorbidities, and the underlying causes of ED [11]. ED can be a symptom of a wide range of underlying pathologies and is an essential but underutilized cardiovascular risk factor. Any disease process that affects penile arteries, nerves, hormone levels, smooth muscle tissue, corporal endothelium, or tunica albuginea can cause erectile dysfunction [55].

Psychosocial factors, particularly stigma and embarrassment associated with ED, often prevent patients from seeking medical help or adhering consistently to prescribed therapies, resulting in suboptimal treatment outcomes. This psychological barrier underscores the importance of integrating patient-centered education and counseling into standard ED management practices.

Treatment adherence is also influenced by practical considerations, including the side effects associated with certain therapeutic options. Although pharmacological treatments such as PDE5 inhibitors are widely effective, common side effects — headaches, flushing, and nasal congestion — may lead to reduced patient compliance or discontinuation. Additionally, invasive treatments such as intracavernosal injections or penile implants, despite high effectiveness, are associated with discomfort or potential complications, influencing patient acceptance and satisfaction.

Access to certain advanced or specialized therapies, including penile Doppler ultrasound, stem cell therapy, and low-intensity shockwave treatment, remains limited due to cost, availability, or infrastructure constraints, especially in resource-limited settings. These accessibility issues further restrict treatment options for patients who might otherwise benefit significantly from advanced interventions.

In conclusion, effective management of ED requires highly individualized approaches that account for variability in treatment response, psychosocial barriers, and accessibility constraints. Addressing these challenges — particularly stigma, adherence barriers, and limited availability of advanced therapies — will be critical to enhancing patient satisfaction and overall treatment success. Emerging therapies such as stem cell treatments and shockwave therapy offer promise for complex or refractory cases but necessitate further research to establish their effectiveness, safety, and long-term patient outcomes.

As the understanding of ED evolves, researchers and clinicians are exploring innovative therapies that target the root causes of the condition rather than merely alleviating symptoms. These emerging interventions focus on regenerative medicine, tissue engineering, and advanced technologies to restore penile function and improve patient outcomes. There is growing evidence suggesting efficacy of intracavernosal stem cells therapy and low-intensity shock wave therapy, although these therapies are still investigational [56].

Stem cell therapy is a leading regenerative approach with potential to repair damaged penile tissue and restore erectile function. Stem cells, typically harvested from adipose tissue or bone marrow, are injected directly into the corpora cavernosa. This promotes angiogenesis, reduces fibrosis, and regenerates smooth muscle tissue, essential for erections [57]. Multiple types of SC were utilized in the treatment of ED: mesenchymal SCs, placental matrix-derived mesenchymal SCs, mesenchymal SC-derived exosomes, adipose-derived SCs, bone marrow-derived mononuclear SCs, and umbilical cord blood SCs [58]. SC therapy shows promise as an innovative and safe treatment for organic ED. However, the lack of standardized techniques and controlled groups in many studies hampers the ability to evaluate and compare trials.

Platelet-rich plasma (PRP) therapy involves injecting concentrated platelets, growth factors, and cytokines into penile tissue to stimulate tissue repair and improve blood flow. PRP promotes neovascularization and tissue regeneration through activation of cellular repair pathways. Despite a global presence of PRP clinics and ongoing active marketing and public interest in regenerative medicine, no scientific evidence has been published to establish an evidence-based risk-benefit profile for PRP use for ED in humans [59]. The first double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of PRP injections suggest improvements in erectile function, particularly for management of mild to moderate ED [60]. Combining PRP with other treatments, such as low-intensity extracorporeal shockwave therapy (LI-ESWT), may further enhance outcomes. These findings still required large-scale clinical trials for verification [61]. Challenges include a lack of large randomized controlled trials, variability in preparation techniques, and regulatory concerns due to unstandardized formulations. Future research aims to standardize protocols, define optimal treatment intervals, and assess long-term efficacy.

LI-ESWT has been investigated for the treatment of uroandrological disorders including ED [21]. It uses low-energy acoustic waves to stimulate growth factors, promoting angiogenesis and reducing fibrosis in penile tissue [62]. Meta-analyses indicate moderate improvements in erectile function, particularly in patients with mild to moderate ED [63]. Additionally, LI-ESWT enhances the effectiveness of PDE5 inhibitors in non-responders [64]. Challenges include variable patient responses based on ED etiology and lack of consensus regarding optimal treatment parameters. Current research efforts are refining protocols and investigating combined therapies, such as LI-ESWT with PRP, to maximize therapeutic benefits.

Gene therapy targets genetic and molecular pathways critical for erectile function. This involves delivering specific genes, such as those encoding nitric oxide synthase or vascular endothelial growth factor, into penile tissue to enhance blood flow and tissue repair. Although gene therapy is a promising option, many challenges and obstacles such as local inflammatory response and random transgene expression, in addition to other safety issues, limit its use at the clinical level [65]. Gene therapy refers to the use of viral and non-viral vectors to deliver therapeutic genes to tissues via direct or transduced cell-mediated approaches. With the growing knowledge on the molecular mechanisms involved in the pathophysiology of ED, a number of therapeutic gene strategies have been extensively tested and proven to be effective in many animal models [66]. Human trials, though limited, are underway to evaluate safety and feasibility. Ethical and regulatory challenges, along with technical difficulties in precise gene delivery, remain significant barriers. Advances in biologically informed deep learning model called BioDeepGWAS and gene-editing technologies like CRISPR offer potential pathways toward personalized treatments [67].

Emerging interventions represent a shift from symptom management toward curative and regenerative treatments for ED. Stem cell therapy, PRP therapy, and LI-ESWT offer significant potential, particularly in refractory cases, while gene therapy present transformative possibilities for future treatment paradigms. However, broad clinical adoption requires addressing significant regulatory, cost-related, and evidence-based challenges. Continued research and innovation will be crucial in moving toward lasting solutions for individuals affected by ED.

ED is a complex, multifaceted condition affecting millions globally, significantly impacting physical, psychological, and social health. This review has comprehensively addressed the current state of ED, examining critical aspects such as diagnosis, management, and emerging therapeutic interventions.

Accurate diagnosis of ED necessitates a multifaceted approach, combining detailed patient history, validated questionnaires like the International Index of Erectile Function (IIEF), through physical examinations, laboratory assessments, and specialized diagnostic techniques such as penile Doppler ultrasound and nocturnal penile tumescence testing. Despite their effectiveness in identifying underlying ED causes, diagnostic tools face ongoing challenges, including patient stigma, underreporting of symptoms, and restricted access to advanced diagnostics in many regions. Overcoming these barriers is essential for timely and precise diagnosis.

Pharmacological interventions, especially PDE5 inhibitors, remain the cornerstone of ED management due to their demonstrated efficacy, safety profile, and high patient acceptance. Nonetheless, non-pharmacological treatments such as vacuum erection devices, penile implants, psychotherapy, and lifestyle adjustments significantly contribute to managing refractory ED cases and improving overall patient quality of life. An integrated and holistic management strategy that encompasses both pharmacological and non-pharmacological therapies is crucial for optimizing patient outcomes.

Emerging therapeutic interventions, including stem cell therapy, PRP, LI-ESWT and gene therapy, represent a transformative shift in ED management. These innovative regenerative treatments offer substantial promise for restoring natural erectile function, especially in complex or refractory cases. Although these approaches are promising, they remain in preliminary clinical stages, and rigorous research is required to conclusively establish their safety, efficacy, and broader clinical accessibility.

Effective ED management holds broader health implications beyond sexual function restoration, potentially serving as an early indicator for systemic diseases such as cardiovascular disorders, diabetes, and hypertension. Addressing ED proactively not only improves individual health but also significantly enhances interpersonal relationships, self-esteem, and overall quality of life. Reducing societal stigma and improving healthcare access, particularly in low-resource areas, are critical steps toward alleviating the global impact of ED.

Future research directions should prioritize the refinement of diagnostic methodologies, personalized treatment development, and improving accessibility to novel therapies. Enhanced collaboration among researchers, healthcare providers, policymakers, and industry stakeholders is essential to propel advancements in ED treatment and to ensure equitable distribution of cutting-edge therapies.

ED remains a significant public health issue, yet recent advancements in diagnosis, therapeutic management, and emerging regenerative interventions offer substantial optimism for better patient outcomes. Continued innovation and multidisciplinary, patient-centered care strategies will be instrumental in achieving lasting improvements for individuals affected by ED, ultimately paving the way toward enhanced sexual health and overall well-being.