What are the most effective treatment options for erectile dysfunction (ED)?

Erectile Dysfunction Treatment

Oral PDE5 inhibitors (sildenafil, tadalafil, vardenafil, or avanafil) should be your first-line pharmacological treatment for erectile dysfunction unless contraindicated, with proper dose titration to maximize efficacy. 1, 2

Initial Assessment and Risk Stratification

Before initiating any ED treatment, you must perform cardiovascular risk assessment because ED precedes coronary artery disease symptoms by 2-5 years and signals substantially increased cardiovascular mortality risk. 3, 2

Stratify patients into three cardiovascular risk categories: 4, 1

• High-risk patients (unstable angina, uncontrolled hypertension, recent MI within 2 weeks, severe heart failure NYHA class II or higher, high-risk arrhythmias, moderate-to-severe valvular disease) should NOT receive ED treatment until cardiac stabilization occurs 4, 1

• Low-risk patients (asymptomatic coronary disease, <3 risk factors for CAD, controlled hypertension, mild stable angina, successful revascularization, uncomplicated past MI, mild valvular disease, CHF class I) may receive all first-line therapies 4

• Intermediate-risk patients require cardiology evaluation before ED treatment 4

Required Laboratory Testing

Order these tests in all men presenting with ED: 3, 2

• Fasting glucose and HbA1c to screen for diabetes, which both causes ED and indicates increased mortality risk 3, 5
• Fasting lipid profile to identify hyperlipidemia and atherosclerotic disease 3, 5
• Total testosterone level (particularly in PDE5 inhibitor non-responders, as adequate testosterone is required for full PDE5 inhibitor efficacy) 3, 2, 6

Treatment Algorithm

First-Line: Lifestyle Modifications

Implement these changes before or concurrent with pharmacotherapy: 1, 2

• Smoking cessation reduces total mortality by 36% in men with coronary disease and improves endothelial function 3, 2
• Regular dynamic exercise reduces incident coronary disease by 30-50% and improves erectile function 2
• Weight loss for obese patients, as obesity significantly increases ED risk 5
• Mediterranean diet emphasizing fruits, vegetables, whole grains, fish, and limiting red meat 3
• Moderate alcohol consumption (<14 units/week for women, <21 units/week for men) 3

Second-Line: Oral PDE5 Inhibitors

Start with any PDE5 inhibitor (sildenafil, tadalafil, vardenafil, or avanafil) as there is insufficient evidence to support superiority of one agent over another. 4, 1, 2 These medications are effective in 60-65% of patients, including those with hypertension, diabetes, spinal cord injury, and other comorbidities. 1, 2, 6

Critical prescribing instructions: 1

• Titrate the dose upward to achieve optimal efficacy rather than accepting suboptimal response at lower doses 1
• Provide explicit instructions on proper use to maximize benefit 1
• Absolute contraindication: Never combine with nitrates—wait 24 hours after sildenafil or vardenafil, and 48 hours after tadalafil before administering nitrates even in emergencies 4

For PDE5 inhibitor non-responders: Check testosterone levels, as these medications require adequate testosterone for full efficacy. 3, 2, 6

Tadalafil-specific efficacy data: 7

• When taken as needed (up to once daily), tadalafil 20 mg produces successful erections in 61-64% of attempts at 24 hours and 62-64% at 36 hours post-dosing 7
• Daily tadalafil (2.5-5 mg) demonstrates sustained efficacy without diminishing treatment effect over 6 months 7

Adjunctive Testosterone Replacement

For men with confirmed hypogonadism (testosterone <230 ng/dL) and symptoms of decreased libido or ED, add testosterone replacement therapy. 3, 2 This improves sexual function and enhances PDE5 inhibitor response. 3, 2

• Men with testosterone 230-350 ng/dL may benefit if symptomatic 3
• Testosterone >350 ng/dL does not usually require replacement 3
• Contraindication: Do not use in men seeking fertility 3, 2

Third-Line: Invasive Therapies

When PDE5 inhibitors fail, escalate to these options: 1, 2

Intracavernosal injection therapy using alprostadil, papaverine, or phentolamine is highly effective for PDE5 inhibitor failures. 1, 3, 2, 6

• Alprostadil produces erections in 5-20 minutes lasting up to one hour 8
• Maximum frequency: 3 times per week with at least 24 hours between injections 8
• Critical warning: If erection persists >6 hours, seek immediate medical attention to prevent permanent penile damage 8

Intraurethral alprostadil suppositories are an alternative for patients unable to use injections. 1, 3, 2

Vacuum constriction devices are non-invasive mechanical options for patients who cannot use or do not respond to pharmacological treatments. 1, 3, 2

Fourth-Line: Surgical Treatment

Penile prosthesis implantation is reserved for patients with refractory ED who fail all less invasive treatments. 1, 3, 2 This option is associated with high patient satisfaction rates. 6

Arterial reconstructive surgery is only appropriate for healthy young men with recently acquired ED secondary to focal arterial occlusion without generalized vascular disease. 4 This is not suitable for typical ED patients with diffuse atherosclerotic disease.

Psychosexual Therapy

Offer psychosexual therapy as adjunctive treatment in combination with medical therapies, particularly for patients with psychogenic ED or psychological contributors. 1, 3, 2 Cognitive-behavioral therapy and relationship counseling improve communication about sexual concerns and reduce performance anxiety. 3, 2

Common Pitfalls to Avoid

• Failing to recognize ED as a cardiovascular disease marker and not screening for diabetes, hypertension, hyperlipidemia, and metabolic syndrome 1, 3, 2
• Not titrating PDE5 inhibitor doses to optimal efficacy when patients report suboptimal response 1
• Ignoring low testosterone levels in PDE5 inhibitor non-responders 3, 2
• Not involving the partner in treatment discussions when possible 3
• Prescribing PDE5 inhibitors to high-risk cardiac patients without cardiac stabilization 4, 1