An In-Depth Review of Erectile Dysfunction and Ejaculation Disorders: Pathophysiology, Diagnostic Approaches, and Multimodal Therapeutic Strategies

1.1 Definition of Erectile Dysfunction (ED) and Ejaculation Disorders (EjD)

Erectile dysfunction (ED), sometimes termed impotence, is classically defined as the persistent or recurrent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. It must be present for a minimum duration (often >3 months) and cause distress to the individual. Ejaculation disorders (EjD) are a heterogeneous group of male sexual dysfunctions involving abnormalities in the timing, control, volume, or force of ejaculation. Common types include premature ejaculation (PE), delayed ejaculation (DE), retrograde ejaculation, anejaculation, decreased ejaculatory force, and perceived ejaculate volume reduction (Office of Ejaculatory Disorders) (Jannini, Lenzi, & Simonelli, 2002; “Office management of ejaculatory disorders,” 2016). PE, in particular, is most often defined by: (i) ejaculation occurring within approximately one minute of vaginal penetration (lifelong PE) or substantially sooner than desired, (ii) inability to delay ejaculation, and (iii) negative personal consequences (e.g., distress) over a period of at least six months (“Premature (Early) Ejaculation DSM?5,” 202??; Patton’s group; Metaanalytic sources) (StatPearls, 2024; Serefoglu et al., 2014).

1.2 Epidemiology and Global Prevalence

ED is common worldwide, but estimates vary widely depending on the population studied, the age range, and methods of assessment. A broad review has reported global ED prevalence in adult men from ~3% to as high as 76.5%. Higher rates are generally seen with increasing age and in populations with comorbid disease, such as cardiovascular disease or diabetes (Ayta, McKinlay, & Krane, 1999; Elterman et al., 2021; “The global prevalence of erectile dysfunction: a review,” 2019). For example, in men aged 40–70 years from eight countries, prevalence was about 49.7% when assessed by self-report of difficulty in achieving or maintaining an erection in the past six months (Elterman et al., 2021).

Among diabetic men, the prevalence is substantially higher: a recent umbrella review found pooled prevalence of ED in diabetic patients globally at ~65.8% (95% CI: 58.3-73.3%) (BMC Public Health, 2024).

Ejaculation disorders are also highly prevalent. Premature ejaculation, in particular, affects approximately 20-30% of men in many studies, although estimates vary based on definition and measurement tools (Office management of ejaculatory disorders, 2016; Premature Ejaculation: Aetiology and Treatment Strategies, 2021). A large systematic review compiling data from 79 prevalence studies across 33 countries found average prevalence of PE at about 14.2% (though with wide standard deviation) with psychogenic ejaculatory complaints dominating over more strictly defined impaired ejaculatory control subtypes (Mw general PE ~14.2%, SD ~15.9%) (Systematic Review, 2024).

1.3 Impact on Quality of Life, Mental Health, and Relationships

ED carries substantial consequences for psychological wellbeing, interpersonal relationships, and partner satisfaction. Men with ED often report decreased self-esteem, increased rates of anxiety and depressive symptoms, frustration, and intimacy difficulties. Female partners may also experience distress, reduced sexual satisfaction, and strain in the relationship (Elterman et al., 2021).

In work contexts, ED is associated with reduced quality of life, lower scores on standard instruments (e.g., SF-36, SF-6D), increased absenteeism and presenteeism, and impaired productivity. For example, men aged 40-70 with ED show higher work productivity impairment and activity impairment compared to peers without ED, and worse mental and physical component summary scores (Elterman et al., 2021).

Ejaculation disorders likewise affect mental health and relationships: chronic PE can lead to relationship discord, significant distress, embarrassment, anxiety, and lowered sexual satisfaction; DE, though less common, also contributes to distress and interpersonal dissatisfaction (StatPearls, 2024; Patton et al., 2021).

1.4 Economic and Healthcare Burden

The burden of ED extends beyond personal suffering—there are direct and indirect economic costs borne by individuals, employers, and healthcare systems. Studies have documented higher healthcare utilization, expenses related to diagnostic tests, medications, device and surgical treatments. Indirect costs include decreased work productivity, absenteeism, and reduced quality of life, which may translate to economic losses for employers and society.

A comparative study in Taiyuan, China found that the total economic burden (direct, indirect, intangible) of ED patients was substantially higher than that of PE patients; in that study ED patients’ mean total economic burden was 16,840.04 yuan vs. 8,717.95 yuan for PE patients, accounting for ~16.4% of per-capita GDP and ~41.5% of per-capita disposable income in the locale (Fu et al., 2024). In multinational surveys, men with ED report significantly greater absenteeism and decreased work productivity compared to men without ED, with measurable decrements in work output corresponding with ED severity (Elterman et al., 2021).

Healthcare systems also face challenges: underdiagnosis, stigma, variable access to effective treatments, and often fragmented care across urology, endocrinology, psychiatry/psychology, which adds both to direct costs (clinic visits, pharmaceuticals, procedures) and system inefficiency.

1.5 Need for an Updated Comprehensive Review

Despite a large cumulative research base, several gaps persist that justify an updated review:

1. Variability in Definitions: Different studies use different definitions (e.g., varying latency times for PE, thresholds for ED), which complicates comparison and meta-analysis.
2. New Epidemiologic Data: More recent prevalence studies, including among specific disease populations (e.g., diabetics, cardiovascular disease, psychiatric disorders), have become available, potentially altering our understanding of global and regional burden.
3. Emerging Diagnostic Tools and Biomarkers: Advances in imaging, molecular markers, and psychometric assessments may enable more precise characterization of dysfunction.
4. Therapeutic Innovations: Newer therapeutic options (e.g. regenerative medicine, combination behavioral and pharmacologic strategies) necessitate an updated assessment of what works, for whom, and under what conditions.
5. Holistic Outcomes: Increasing recognition that sexual dysfunction affects not just physical functioning but mental health, relational health, economic functioning, and quality of life, and that these outcomes are under-reported in older analyses.

Thus, an in-depth, up-to-date review integrating pathophysiology, diagnostic approaches, and multimodal treatment strategies is needed to inform research, clinical practice, and health policy.

2. Pathophysiology of Erectile Dysfunction

Erectile function is a complex, integrated process requiring intact vascular, neurologic, hormonal, and psychological systems. Disruption in any one (or more) of these domains can produce erectile dysfunction (ED).

2.1 Vascular Mechanisms

2.1.1 Endothelial dysfunction

Normal penile erection depends on coordinated relaxation of cavernosal smooth muscle and increased arterial inflow, processes that are critically dependent on endothelial health. Endothelial dysfunction (reduced nitric oxide bioavailability, increased oxidative stress, impaired vasodilatory response) leads to inadequate arterial inflow and impaired trabecular smooth muscle relaxation, producing or aggravating ED (Burnett, 2006; Carella et al., 2023).

2.1.2 Role of nitric oxide and cyclic GMP pathway

Nitric oxide (NO), released from nonadrenergic noncholinergic nerves and from vascular endothelium in the corpora cavernosa, activates soluble guanylate cyclase in smooth muscle cells, increasing cyclic guanosine monophosphate (cGMP) and causing smooth muscle relaxation and vasodilation. Impaired NO production or increased NO degradation (e.g., by oxidative stress) reduces cGMP signaling and limits the erectile response — a central mechanistic explanation for why PDE5 inhibitors (which preserve cGMP) are effective in many patients (Burnett, 2006; Toda & Burnett, 2005).

2.1.3 Atherosclerosis and hypertension-related changes

Atherosclerotic narrowing of penile arteries and small-vessel disease reduce penile perfusion. Because the penile arteries are smaller than coronary arteries, clinical ED may precede symptomatic coronary artery disease, making ED an early marker of systemic atherosclerosis. Chronic hypertension promotes vascular remodeling and endothelial dysfunction, further increasing ED risk (Elesber et al., 2006; Peng, 2024).

2.2 Neurogenic Factors

2.2.1 Central nervous system regulation

Erection requires supraspinal (hypothalamus, limbic structures) and spinal cord integration. Central neurotransmitters (dopamine, serotonin, oxytocin, and NO in hypothalamic nuclei) modulate libido and erectile responses. Central neurologic diseases (e.g., Parkinson’s disease, stroke, multiple sclerosis) can disrupt these pathways and cause ED (Melis & Argiolas, 2021).

2.2.2 Peripheral nerve injury (e.g., diabetes, pelvic surgery)

Peripheral autonomic and somatic nerves supply the penis; injury from pelvic surgery (e.g., radical prostatectomy), pelvic trauma, or diabetic peripheral neuropathy can impair nerve-mediated NO release and reflexogenic erection. Diabetes both damages nerves and accelerates vascular disease, producing a mixed neurovascular ED phenotype that is particularly treatment-resistant (Defeudis et al., 2021; Shridharani & Hollenbeck, 2016).

2.3 Hormonal Influences

2.3.1 Testosterone deficiency

Androgens, especially testosterone, are important for libido and erectile tissue integrity. Hypogonadism reduces sexual desire and may impair erectile physiology through trophic effects on penile tissue and modulation of NO synthase expression. Testosterone replacement improves libido and sometimes erectile function in hypogonadal men, although response is variable and often incomplete when vascular or neurologic disease predominates (Rajfer & Gonzalez-Cadavid, 2000).

2.3.2 Hyperprolactinemia, thyroid disorders

Hyperprolactinemia suppresses gonadotropin release and testosterone synthesis and is associated with decreased libido and ED; treatment of prolactin-secreting adenomas often improves sexual function (Zeitlin, 2000). Thyroid dysfunction (both hypo- and hyperthyroidism) can also impair erectile function and sexual desire, and correction of thyroid disease commonly restores erectile function in affected men (Krassas et al., 2008).

2.4 Psychogenic Contributions

2.4.1 Anxiety, depression, stress, performance anxiety

Psychological factors can initiate or perpetuate ED. Performance anxiety and generalized anxiety often precipitate sympathetic overactivity, which antagonizes the parasympathetic vasodilator responses needed for erection. Depression is strongly associated with diminished libido and erectile problems; antidepressant therapy (particularly SSRIs) can also worsen ejaculatory and erectile function (StatPearls, 2024; Serefoglu et al., 2014).

2.4.2 Relationship dynamics

Interpersonal factors — poor communication, unresolved sexual or emotional conflicts, partner sexual dysfunction — frequently contribute to or maintain ED. Assessment of relationship context and partner involvement are essential for effective management (Elterman et al., 2021).

2.5 Iatrogenic Causes

2.5.1 Drug-induced ED (antidepressants, antihypertensives, chemotherapy)

Multiple commonly used medications can cause or worsen ED. Examples include many antihypertensives (especially older agents such as thiazides and beta-blockers in some patients), certain antidepressants (SSRIs and some TCAs), antipsychotics (through prolactin elevation), and some chemotherapeutic agents (through gonadal toxicity or neuropathy). When ED appears after starting a drug, review and medication adjustment (where possible) is a key step in management (StatPearls, 2024; Mazzilli et al., 2022).

Table 1. Pathophysiology of Erectile Dysfunction (ED)

3. Pathophysiology of Ejaculation Disorders

Ejaculation is a tightly regulated reflex involving cortical and brainstem centers, spinal ejaculatory generators, peripheral somatic and autonomic nerves, and end-organ tissues (bulbospongiosus and pelvic floor muscles). Disruption at any level — central neurotransmitter imbalance, altered spinal circuits, peripheral neuropathy, endocrine disturbance, or mechanical/structural failure (e.g., bladder neck incompetence) — can produce clinically significant ejaculatory disorders such as premature ejaculation (PE), delayed ejaculation (DE), retrograde ejaculation (RE), and anejaculation (AN).

3.1 Premature Ejaculation (PE)

3.1.1 Neurobiological basis (serotonin pathways, penile hypersensitivity)

PE is most consistently linked to dysfunction of central serotonergic circuits that normally inhibit the ejaculatory reflex. Higher serotonin (5-HT) activity at inhibitory 5-HT receptor subtypes (e.g., 5-HT?C, 5-HT?B) and lower activity at facilitatory subtypes (e.g., 5-HT?A) influence ejaculatory latency; pharmacologic agents that increase synaptic serotonin (SSRIs, clomipramine) prolong latency, supporting this model (Gillman, 2019; Raveendran, 2021). In addition to central neurotransmitters, heightened penile sensory input (penile hypersensitivity) — whether primary (idiopathic, genetic) or secondary (inflammation, infection) — can lower ejaculatory thresholds and contribute to lifelong or acquired PE (Van Raaij, 2023; Kalejaiye, 2017). Recent genetic and neurophysiologic work suggests a heterogeneous etiology in which serotonergic, dopaminergic, oxytocinergic and peripheral sensory factors interact to determine individual susceptibility (Van Raaij, 2023; Gillman, 2019).

3.1.2 Psychological and behavioral factors

Psychological precipitants — performance anxiety, relationship stress, conditioned rapid response patterns developed early in sexual history, and situational factors (new partner, guilt) — can initiate or perpetuate PE. Behavioral techniques (stop-start, squeeze) and psychosexual counseling target learned components and partner dynamics; combined pharmacologic and behavioral approaches often produce the best outcomes (Martin, 2017; Raveendran, 2021).

3.2 Delayed Ejaculation (DE)

3.2.1 Neuroendocrine alterations

DE (including delayed orgasm and anorgasmia) is mechanistically diverse. Central neurotransmitter imbalances — particularly excess serotonergic tone and decreased dopaminergic signaling — are implicated, as serotonin suppresses and dopamine facilitates ejaculation and orgasmic responses. Hormonal disruptions (hypogonadism, hyperprolactinemia) and thyroid disease can also impair ejaculatory/ orgasmic function via modulation of central drive and peripheral genital sensitivity (Nguyen, 2024; Otani, 2019).

3.2.2 Medication-induced causes (SSRIs, antipsychotics)

Pharmacologic agents are a frequent and often reversible cause of DE. SSRIs are classically linked to delayed ejaculation and anorgasmia through enhanced serotonergic inhibition of spinal ejaculatory centers and indirect suppression of dopaminergic reward pathways; antipsychotics (especially prolactin-elevating agents) also contribute through hyperprolactinemia and dopamine blockade. Recognition of medication timing and dose relationships is critical because dose reduction, switching to a less problematic agent, or drug holidays (when clinically safe) may improve symptoms (AUA/SMSNA, 2020; Nguyen, 2024; Tran, 2022).

3.3 Retrograde Ejaculation (RE)

3.3.1 Bladder neck dysfunction

Retrograde ejaculation occurs when the bladder neck (internal urethral sphincter) fails to close during emission so that semen flows backward into the bladder instead of antegrade ejaculation. This can be due to neuropathic dysfunction of autonomic innervation, failure of smooth muscle contraction at the bladder neck, or pharmacologic blockade of α-adrenergic receptors that mediate closure (AUA/SMSNA, 2020; Recent narrative reviews). Conditions that impair bladder neck closure include diabetes autonomic neuropathy, postsurgical damage, and drugs (e.g., α-blockers used for BPH) (Konstantinidis, 2025; Recent RE reviews, 2025).

3.3.2 post-surgical and neuropathic etiologies

Transurethral or open prostate/bladder neck surgery (e.g., transurethral resection/incision of the prostate or bladder neck procedures) commonly cause RE by mechanical disruption of the bladder neck. Spinal cord injury and pelvic autonomic neuropathy (e.g., diabetic autonomic neuropathy) also interrupt the efferent sympathetic pathways necessary for emission and bladder neck closure (Primary bladder neck obstruction and RE literature; Otani, 2019; Soni, 2022).

3.4 Anejaculation (AN)

3.4.1 Neurological lesions

Anejaculation — total absence of ejaculation despite sexual stimulation — often reflects severe interruption of the ejaculatory reflex arc. Lesions to spinal ejaculatory generators, sacral roots, or peripheral autonomic nerves (e.g., high spinal cord injury, severe diabetic neuropathy) can abolish the ejaculatory pattern; experimental and clinical studies have identified specific spinal and supraspinal neuronal populations responsible for ejaculation that, when disrupted, produce anejaculation (Soni, 2022; Otani, 2019).

3.4.2 Endocrine dysfunctions

Endocrine disorders (marked hypogonadism, profound hyperprolactinemia, severe hypothyroidism) may blunt libido and central ejaculatory drive to the point of anejaculation. Correction of the endocrine abnormality can restore ejaculatory function in some cases, highlighting the importance of endocrine assessment in unexplained anejaculation (AUA/SMSNA, 2020; Gillman, 2019).

Table 2. Pathophysiology of Ejaculation Disorders (EjD)

4. Diagnostic Approaches

A structured, stepwise diagnostic approach improves detection of the underlying causes of erectile and ejaculatory disorders and guides targeted therapy. Evaluation commonly begins with history and questionnaires, proceeds through focused physical examination, directed laboratory testing, and—when indicated—imaging or functional testing.

4.1 Patient History and Sexual Function Questionnaires

A detailed sexual, medical, and psychosocial history is the single most important part of the diagnostic evaluation. Key elements include onset (lifelong vs. acquired), timing and context (situational vs. generalized), comorbidities (diabetes, cardiovascular disease, psychiatric illness), medications, substance use, relationship factors, nocturnal erections, and fertility concerns (Burnett et al., 2018; Salonia et al., 2024).

Validated questionnaires standardize assessment and are useful for diagnosis, severity grading, and monitoring treatment response:

• International Index of Erectile Function (IIEF-15 / IIEF-5) — The IIEF-15 measures five domains (erectile function, orgasmic function, sexual desire, intercourse satisfaction, overall satisfaction); the abbreviated IIEF-5 (SHIM) is widely used for screening and grading ED severity (Rosen, 1997). The IIEF-5 scoring ranges (22–25: no ED; 17–21: mild; 12–16: mild-to-moderate; 8–11: moderate; 5–7: severe) are helpful for baseline stratification and outcome tracking (Rosen, 1997; Uroweb, 2024).
• Premature Ejaculation Diagnostic Tool (PEDT) — A brief 5-item questionnaire validated to screen for PE and assess severity; scores ≥11 is suggestive of PE, with higher scores indicating greater likelihood/severity (Symonds et al., 2007; Tang et al., 2017).

Use questionnaires in combination with history (e.g., estimated intravaginal ejaculation latency time when relevant) and partner input when possible (Burnett et al., 2018).

4.2 Physical Examination

A focused physical exam evaluates genital anatomy and signs of systemic disease:

• Genital exam: inspect penis and scrotum for Peyronie’s disease, penile curvature, scars/trauma; palpate testes for size, consistency (small, soft testis suggest hypogonadism); examine epididymis and vas deferens if fertility concerns exist (EAU, 2024).
• Secondary sexual characteristics: assess body habitus, gynecomastia, body hair distribution; these provide clues to chronic androgen deficiency or endocrinopathy (Salonia et al., 2024).
• Neurological assessment: test perineal sensation, bulbocavernosus reflex, and sacral reflexes when neuropathy or spinal disease is suspected (AUA, 2018).
• Vascular assessment: peripheral pulses, ankle–brachial index when atherosclerotic disease risk is present; look for signs of peripheral vascular disease and hypertension (AUA, 2018).

Document findings that could explain erectile dysfunction (e.g., priapism sequelae, previous pelvic surgery) and guide further testing.

4.3 Laboratory Investigations

Laboratory testing should be individualized based on history and physical exam; routine baseline work commonly includes:

• Hormonal profile: early-morning total testosterone (and free testosterone if indicated), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and thyroid-stimulating hormone (TSH) when signs/symptoms suggest endocrine disorder—particularly in men with low libido, small testes, or other features of hypogonadism (Salonia et al., 2024; Porav-Hodade et al., 2025).
• Metabolic parameters and cardiovascular risk markers: fasting glucose or HbA1c, fasting lipid profile, and blood pressure assessment because diabetes, dyslipidemia, and metabolic syndrome are strongly associated with ED (AUA, 2018; BSSM/consensus statements).
• Other tests as indicated: liver/renal function, serum electrolytes, and specialized endocrine testing (e.g., morning cortisol) when clinically warranted.

Routine testing protocols vary by guideline and clinical context; many centers obtain fasting glucose/HbA1c, lipid profile, and morning testosterone as baseline studies for men presenting with ED (BSSM review; Salonia et al., 2024).

4.4 Imaging and Functional Tests

Second-line investigations are reserved for diagnostic uncertainty, suspected structural/vascular disease, or when invasive/advanced therapy is being considered.

• Penile Doppler ultrasound (PDUS): Dynamic duplex ultrasonography after intracavernosal vasoactive agent injection assesses arterial inflow (peak systolic velocity) and veno-occlusive function (end-diastolic velocity). PDUS is useful to characterize vasculogenic ED, guide expectations for treatment, and plan vascular interventions in selected patients (Varela et al., 2020; Flores et al., 2024). Interpretation must consider timing, protocol, and operator experience.
• Nocturnal penile tumescence (NPT) / Nocturnal penile tumescence and rigidity (NPTR): Home or laboratory devices (e.g., RigiScan) document spontaneous nocturnal erections, helping distinguish psychogenic from organic ED. Normal NPT suggests preserved physiologic erectile capacity; abnormal NPTR supports organic causes. Cutoffs vary, but many studies regard penile tip rigidity ≥60% for ≥10 minutes as a normal event (Zou et al., 2019; Elhanbly et al., 2018). NPT has limitations (patient compliance, false positives/negatives) and is used selectively.
• Neurophysiological studies: When neuropathy or neurologic disease is suspected (e.g., spinal cord injury, multiple sclerosis), pudendal nerve testing, bulbocavernosus reflex latency, and other specialized neurophysiology can be helpful (EAU, 2024).
• Advanced cardiovascular evaluation: Because ED can be a harbinger of systemic atherosclerotic disease, selected patients—particularly those with risk factors and new-onset ED—may need cardiovascular risk evaluation and, in some cases, stress testing or cardiology referral (AUA, 2018).

Utility of these tests should be balanced against cost, invasiveness, and impact on management decisions. Many men do not require advanced testing if the history, exam, and basic labs point to an obvious reversible cause or if empiric therapy (e.g., PDE5 inhibitor) is appropriate.

Table 3. Basic diagnostic workup for erectile dysfunction (recommended tests and indications)

Table 4. Practical tips for outpatient evaluation

5. Therapeutic Strategies

The management of erectile dysfunction (ED) and ejaculation disorders (EjD) is multimodal, often requiring a combination of lifestyle changes, pharmacological interventions, devices, psychological therapies, and, in refractory cases, surgical or experimental approaches. Selection of therapy should be tailored to etiology, severity, comorbidities, patient preference, and partner considerations.

Table 5. Therapeutic Strategies for ED and EjD

5.1 Lifestyle and Psychosocial Interventions

• Lifestyle modification: Evidence supports lifestyle optimization as the first-line strategy, particularly in patients with vasculogenic ED. Weight reduction, adherence to Mediterranean or plant-based diets, increased physical activity, and smoking/alcohol cessation significantly improve erectile function and overall sexual health (Esposito et al., 2004; Sansone et al., 2021).
• Stress management and psychotherapy: Psychological factors (stress, anxiety, depression, performance anxiety) exacerbate ED and EjD. Cognitive-behavioral therapy (CBT), mindfulness-based interventions, and psychosexual counseling improve outcomes, particularly in combination with pharmacotherapy (Melnik & Abdo, 2018; Wylie et al., 2022).
• Sex therapy: In PE, behavioral techniques such as the stop–start or squeeze method remain useful adjuncts. Couples-based interventions strengthen communication, reduce relational distress, and improve adherence (Symonds et al., 2007).

5.2 Pharmacological Therapies for ED

• Phosphodiesterase type-5 inhibitors (PDE5i): First-line therapy for ED includes sildenafil, tadalafil, vardenafil, and avanafil. They enhance nitric oxide–cGMP pathways and improve erectile rigidity across etiologies. Efficacy rates reach 60–80% in most populations; contraindications include nitrate therapy and unstable cardiovascular disease (Burnett et al., 2018; Salonia et al., 2024).
• Hormone replacement therapy (HRT): Testosterone replacement is recommended for hypogonadal men with ED and low libido, either alone or in combination with PDE5i for improved response. Monitoring is essential for hematocrit, PSA, and cardiovascular risks (Corona et al., 2022).
• Intracavernosal injections (ICI) and intraurethral agents: Alprostadil (prostaglandin E1), papaverine, and phentolamine (alone or as combinations such as trimix) provide high efficacy in men unresponsive to PDE5i. Intraurethral alprostadil (MUSE®) offers less invasive delivery but lower success rates compared to ICI (Carson et al., 2019).

Table 6. Common medication classes associated with ED

5.3 Pharmacological Therapies for Ejaculation Disorders

Premature Ejaculation (PE):

• SSRIs (paroxetine, sertraline, fluoxetine, and short-acting dapoxetine) delay ejaculation by increasing serotonergic inhibition of the spinal ejaculatory reflex. Dapoxetine is the only approved on-demand oral SSRI for PE in many regions (Kobori et al., 2020).
• Topical anesthetics (lidocaine–prilocaine creams or sprays) reduce penile hypersensitivity; metered-dose sprays provide better consistency and minimize transvaginal numbness (Wyllie et al., 2020).

Delayed Ejaculation (DE) and Anejaculation:

• Dopaminergic agents (cabergoline, bupropion, amantadine) are experimental options, especially for SSRI-induced DE (Nguyen et al., 2024).
• Hormone therapy (testosterone, addressing hyperprolactinemia or thyroid disorders) may correct endocrine-related EjD.

Retrograde Ejaculation (RE):

• Sympathomimetic drugs (pseudoephedrine, imipramine, midodrine) increase bladder neck tone and may restore antegrade ejaculation in selected patients (Konstantinidis, 2025).

Table 7. Medications commonly implicated in ejaculatory disorders

5.4 Mechanical and Device-Based Therapies

• Vacuum erection devices (VEDs): Create negative pressure to draw blood into the penis, maintained with constriction rings. Effective in men unable or unwilling to use pharmacotherapy, also valuable post-prostatectomy for penile rehabilitation (Levine et al., 2020).
• Penile constriction rings: Assist in maintaining erection in men with veno-occlusive dysfunction; used alone or with VEDs.

5.5 Surgical Options

• Penile prostheses: Inflatable and malleable prostheses provide the highest long-term satisfaction among ED therapies when pharmacological options fail (Montague et al., 2020). Inflatable prostheses allow more natural erection–flaccidity transitions, though mechanical failures require revision.
• Vascular surgery: Rarely performed, reserved for young men with isolated penile arterial occlusion due to trauma. Venous ligation surgery is largely abandoned due to poor long-term efficacy (Salonia et al., 2024).

5.6 Emerging and Experimental Therapies

• Stem cell therapy: Adipose-derived stem cells, bone marrow stem cells, and mesenchymal stem cells show promise in restoring erectile tissue integrity and neural regeneration in preclinical and early-phase clinical trials (Soebadi et al., 2020).
• Low-intensity extracorporeal shockwave therapy (Li-ESWT): Induces angiogenesis and improves endothelial function in vasculogenic ED. Randomized controlled trials report improved IIEF scores, though protocols remain heterogeneous (Dong et al., 2019).
• Gene therapy and regenerative medicine: Delivery of endothelial nitric oxide synthase (eNOS) genes, VEGF, and other factors are under investigation; still experimental with regulatory hurdles (Neto et al., 2021).

Table 8. Overview of pharmacologic therapies for ED and EjD