What are the treatment options for erectile dysfunction?

Treatment of Erectile Dysfunction

First-Line Treatment: PDE5 Inhibitors

Oral PDE5 inhibitors (sildenafil, tadalafil, vardenafil, or avanafil) are the recommended first-line therapy for erectile dysfunction unless contraindicated. 1, 2

Efficacy and Success Rates

• PDE5 inhibitors achieve successful sexual intercourse in approximately 69% of patients compared to 35% with placebo 3, 1
• All FDA-approved agents demonstrate similar efficacy in the general ED population, with improvement in erections ranging from 73-88% versus 26-32% for placebo 3, 1, 2
• These medications work across diverse patient populations including those with diabetes, cardiovascular disease, depression, prostate cancer, multiple sclerosis, and renal failure 3

Choosing the Right PDE5 Inhibitor

Select between PDE5 inhibitors based on pharmacokinetic differences and patient lifestyle preferences rather than efficacy, since all work equally well. 1

• Tadalafil has a 17.5-hour half-life providing a 36-hour window of opportunity, making it ideal for men who prefer spontaneity and has lower rates of flushing 1, 4
• Sildenafil and vardenafil have similar molecular structures with approximately 4-hour half-lives 4
• Tadalafil is unaffected by food intake, while fatty meals impair absorption of sildenafil and vardenafil 4
• Onset of action varies: 35% achieve successful intercourse within 14 minutes with sildenafil, 21% within 10 minutes with vardenafil, and 16% within 16 minutes with tadalafil 4

Dosing Strategy

• Start tadalafil at 10mg as needed, can increase to 20mg 1
• Begin with standard dosing and titrate to maximum tolerated dose before declaring treatment failure 1, 5
• An adequate trial requires at least 5 separate occasions at the maximum dose before considering the medication ineffective 1
• Higher doses provide greater efficacy for sildenafil (50mg vs 25mg) and vardenafil, but not for tadalafil 3
• Higher doses increase risk of adverse effects 1, 2

Common Adverse Effects

• Most frequently reported: headache, flushing, nasal congestion, dyspepsia, back pain, myalgia, visual disturbances, and dizziness 1, 2, 5
• These adverse events are generally mild to moderate 1
• Avanafil has lowest rates of dyspepsia, tadalafil has lowest rates of flushing, and vardenafil/avanafil have lowest rates of myalgia 5

Critical Contraindications and Safety Considerations

Never prescribe PDE5 inhibitors to patients taking nitrates—this combination causes potentially fatal hypotension. 1, 2, 5

High-Risk Cardiac Patients (Defer Treatment Until Stabilized)

• Unstable or refractory angina 1, 5
• Uncontrolled hypertension 1, 5
• Left ventricular dysfunction/CHF (NYHA class II or greater) 1, 5
• MI or stroke within previous 2 weeks 1, 5
• High-risk arrhythmias 1, 5
• Hypertrophic obstructive cardiomyopathies 1, 5
• Moderate-to-severe valvular disease 1, 5

Special Dosing Considerations

• Alpha-blocker users: Start on the lowest recommended dose of PDE5 inhibitor due to risk of symptomatic hypotension 1, 6
• Moderate hepatic impairment (Child-Pugh B): Start vardenafil at 5mg with maximum dose of 10mg 6
• Severe hepatic or renal disease: PDE5 inhibitors not recommended 2
• Moderate-to-severe renal impairment: Vardenafil AUC increases 20-30% 6
• Spinal cord injury: Use lower initial doses due to potential delayed metabolism 1, 5

Additional Warnings

• Avoid PDE5 inhibitors in patients with congenital QT prolongation or those taking Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmics 6
• Use with caution in patients with anatomical penile deformation, Peyronie's disease, or conditions predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia) 6, 7
• Stop all PDE5 inhibitors and seek immediate medical attention for sudden vision loss (possible NAION) or sudden hearing loss 6

Lifestyle Modifications

Counsel all ED patients on risk factor modification regardless of pharmacologic treatment. 1

• Recommend smoking cessation, weight loss if overweight, increasing physical activity, avoiding excess alcohol consumption 1
• Optimize management of diabetes, hypertension, and dyslipidemia 1

Hormonal Testing

Do not routinely measure testosterone in all ED patients—individualize based on clinical presentation. 1, 2

• Measure testosterone levels when patients present with decreased libido, premature ejaculation, fatigue, testicular atrophy, or muscle atrophy 1
• Testosterone therapy is not indicated for ED treatment in patients with normal testosterone levels 2

Maximizing Treatment Success

• Incorrect medication use accounts for a large percentage of treatment failures 2, 5
• Provide clear instructions on the importance of sexual stimulation, multiple trials, and timing relative to meals 2
• Periodic follow-up is necessary to assess efficacy, side effects, and any significant changes in health status or medications 5

Second-Line Therapies

If PDE5 inhibitors fail after adequate trial, proceed to second-line interventions. 1

• Intraurethral alprostadil suppositories 1, 7
• Intracavernous vasoactive drug injection (alprostadil) 1, 7
• Vacuum constriction devices 1, 2

Intracavernous Alprostadil Considerations

• Indicated for erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology 7
• Should produce erection in 5-20 minutes lasting up to one hour 7
• Use no more than 3 times per week with at least 24 hours between injections 7
• Seek immediate medical attention if erection lasts more than 6 hours to prevent permanent damage 7
• Contraindicated in men with conditions causing prolonged erections (sickle cell anemia/trait, leukemia, multiple myeloma), penile implants, or severe penile curvature 7

Third-Line Therapy

• Penile prosthesis implantation is the definitive third-line intervention for refractory ED 1

Special Population Considerations

• Men with diabetes have more severe ED at baseline and respond less robustly to PDE5 inhibitors 1, 5
• Post-prostatectomy patients show reduced response to PDE5 inhibitors compared to the general population 1, 5
• Men with predominantly psychogenic ED remain candidates for PDE5 inhibitors as first-line therapy, with referral to psychotherapist as alternative or adjunct 5