What are the causes and treatment options for erectile dysfunction?

Erectile Dysfunction: Causes and Treatment

Causes of Erectile Dysfunction

Erectile dysfunction results from vascular, endocrine, neurological, anatomical, psychological, or medication-related etiologies, with cardiovascular disease being the most critical to identify given that ED symptoms precede coronary artery disease by 2-5 years. 1, 2

Vascular Causes (Most Common)

• Hypertension, atherosclerosis, hyperlipidemia, and endothelial dysfunction represent the primary vascular contributors to ED 2
• ED functions as an independent risk marker for cardiovascular disease with predictive value equivalent to cigarette smoking or family history of myocardial infarction 3
• New onset or progressive ED signals threatening ischemic heart disease even at asymptomatic stages 2

Endocrine Causes

• Diabetes mellitus causes both vascular damage and autonomic neuropathy, with diabetic men showing more severe ED and reduced response to treatment 3, 2
• Hypogonadism (testosterone <300 ng/dL) impairs erectile function and reduces PDE5 inhibitor efficacy 3, 1
• Hyperprolactinemia and thyroid disorders contribute to ED 2

Neurological Causes

• Spinal cord injury, multiple sclerosis, Parkinson's disease, and peripheral neuropathy disrupt the neural pathways required for erection 2
• Autonomic neuropathy causes decreased smooth muscle relaxation of the corpus cavernosum and insufficient nitric oxide synthase function 2

Anatomical/Structural Causes

• Peyronie's disease, penile trauma, and surgical complications (particularly post-prostatectomy) cause ED 3, 2
• Post-prostatectomy patients demonstrate more severe baseline ED and respond less robustly to PDE5 inhibitors 3

Psychological Causes

• Depression, anxiety, stress, and relationship problems contribute to or exacerbate ED 3, 2
• Depression is both a cause and consequence of ED, with worsening depressive symptoms often preceding ED onset 2

Medication-Induced Causes

• Antihypertensives (β-blockers, vasodilators, central sympathomimetics, ganglion blockers, diuretics, ACE inhibitors) associate with ED 2
• Antidepressants (both tricyclics and SSRIs) commonly cause sexual dysfunction 2

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Treatment Algorithm

Step 1: Cardiovascular Risk Assessment (Mandatory First Step)

All men with ED require cardiovascular risk stratification before initiating any treatment, as ED precedes coronary symptoms by 2-5 years and indicates substantially increased cardiovascular mortality risk. 1, 2

• Screen for diabetes (fasting glucose, HbA1c), hypertension, hyperlipidemia (lipid profile), and metabolic syndrome 1, 2
• Stratify patients into low, intermediate, or high cardiovascular risk categories using Princeton Consensus Panel guidelines 4
• High-risk patients must not receive ED treatment until cardiac stabilization is achieved 1, 4
• Communicate cardiovascular risk to the patient, partner, and primary care provider for appropriate referrals 3

Step 2: Laboratory Testing

• Measure total testosterone levels in all men with ED, particularly those who fail PDE5 inhibitors 1, 2
• Testosterone <230 ng/dL indicates hypogonadism requiring replacement therapy 1
• Testosterone 230-350 ng/dL may benefit from replacement if symptomatic 1
• Fasting glucose, lipid profile, and HbA1c identify metabolic contributors 1, 2

Step 3: First-Line Management - Lifestyle Modifications

Lifestyle changes must be implemented in all patients regardless of subsequent pharmacotherapy, as they reduce cardiovascular mortality by 36% and improve endothelial function. 1

• Smoking cessation reduces total mortality by 36% in men with coronary disease and improves endothelial function 1, 2
• Regular dynamic exercise reduces incident coronary disease by 30-50% and improves erectile function 1
• Weight loss and Mediterranean diet (fruits, vegetables, whole grains, fish, limited red meat) improve endothelial function 1, 2
• Moderate alcohol consumption (<14 units/week for women, <21 units/week for men) 1

Step 4: Second-Line Management - Oral PDE5 Inhibitors

PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) are first-line pharmacotherapy for ED, effective in 60-65% of patients, and should be offered to all men without contraindications. 3, 1, 4

Prescribing Guidelines:

• Provide instructions to maximize efficacy: take approximately 60 minutes before sexual activity, sexual stimulation required for effect 3, 5
• Titrate dose to optimal efficacy - higher doses improve erectile function for sildenafil and vardenafil but increase adverse effects 3
• Tadalafil on-demand versus daily dosing produces equivalent efficacy 3

Contraindications and Precautions:

• Absolute contraindication: concurrent nitrate use (regular or intermittent) - can cause life-threatening hypotension 3, 5, 6
• If nitrates needed emergently after tadalafil, wait at least 48 hours after last dose 6
• Caution with alpha-blockers - start PDE5 inhibitor at lowest dose due to additive hypotensive effects 3, 5
• Avoid in patients with congenital QT prolongation or taking Class IA/III antiarrhythmics 5
• Dose adjustment required for moderate hepatic impairment (start vardenafil 5 mg, max 10 mg) 5

Common Adverse Effects:

• Dyspepsia, headache, flushing, back pain, nasal congestion, myalgia 3
• Rare: sudden vision loss (NAION), sudden hearing loss with tinnitus and dizziness 5

Special Populations:

• Diabetic men and post-prostatectomy patients have more severe baseline ED and respond less robustly to PDE5 inhibitors 3
• PDE5 inhibitors require adequate testosterone levels for full efficacy - check testosterone in non-responders 1, 2

Step 5: Adjunctive Testosterone Replacement Therapy

For men with confirmed hypogonadism (testosterone <230 ng/dL) and symptoms, testosterone replacement improves sexual function and enhances PDE5 inhibitor response. 1, 2

• Men with testosterone 230-350 ng/dL may benefit if symptomatic 1
• Testosterone >350 ng/dL does not usually require replacement 1
• Contraindicated in men seeking fertility 1, 2
• Requires interval monitoring of hemoglobin, serum transaminase, and prostate-specific antigen due to increased prostate adenocarcinoma risk 7

Step 6: Psychosexual Therapy (Adjunctive)

For men with predominantly psychogenic ED or psychological contributors, psychotherapy should be offered as either alternative or adjunct to medical treatment. 3, 1, 4

• Cognitive-behavioral therapy and relationship counseling improve communication about sexual concerns and reduce performance anxiety 1, 2
• Partner involvement is essential for improving treatment outcomes 2, 4

Step 7: Third-Line Management - Invasive Therapies (For PDE5 Inhibitor Failures)

Intracavernosal injection therapy using alprostadil, papaverine, or phentolamine is effective for patients who fail or cannot use oral medications. 1, 2, 4, 8

• Intracavernosal injection remains the "golden standard" based solely on effectiveness 9
• Intraurethral alprostadil suppositories are an alternative local therapy option 1, 2, 4
• Vacuum constriction devices are a non-invasive mechanical option for patients who cannot use or do not respond to pharmacological treatments 1, 2, 4

Step 8: Fourth-Line Management - Surgical Options (For Refractory Cases)

Penile prosthesis implantation is reserved for patients with refractory ED who fail all less invasive treatments, with high satisfaction rates and low device failure/infection risks. 1, 2, 4, 10, 8

• Multicomponent inflatable penile implants are associated with high patient satisfaction 8
• Arterial reconstructive surgery is only appropriate for healthy individuals with recently acquired ED secondary to focal arterial occlusion without generalized vascular disease 2
• Penile arterial revascularization and venous ligation surgery have relatively poor outcomes in men with penile atherosclerotic disease 8

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Critical Pitfalls to Avoid

• Failure to recognize ED as a cardiovascular disease marker - ED symptoms precede coronary disease by 2-5 years, making cardiovascular screening mandatory 3, 1, 2
• Not checking testosterone in PDE5 inhibitor non-responders - adequate testosterone is required for full PDE5 inhibitor efficacy 1, 2
• Prescribing PDE5 inhibitors to patients on nitrates - can cause life-threatening hypotension 3, 5, 6
• Not titrating PDE5 inhibitor doses - higher doses improve efficacy but must be balanced against adverse effects 3
• Ignoring psychological contributors - psychosexual factors commonly contribute to or exacerbate ED 3, 4
• Not involving partners in treatment decisions - partner involvement improves outcomes 2, 4