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 definitive first-line treatment for erectile dysfunction unless contraindicated. 1, 2

Efficacy and Evidence Base

• PDE5 inhibitors achieve successful sexual intercourse in approximately 69% of patients compared to 35% with placebo, representing a clinically meaningful improvement 3, 1
• All FDA-approved agents (sildenafil, tadalafil, vardenafil, avanafil) demonstrate equivalent efficacy in the general ED population 1, 4
• These medications improve erectile function across a broad range of patients, including those with diabetes, cardiovascular disease, depression, prostate cancer, multiple sclerosis, and renal failure 3

Selecting the Right PDE5 Inhibitor

Choose between PDE5 inhibitors based on pharmacokinetic differences and patient lifestyle preferences, not 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, 5
• Sildenafil and vardenafil have similar 4-hour half-lives and molecular structures, with faster onset but shorter duration 5
• Food (especially fatty meals) affects absorption of sildenafil and vardenafil but not tadalafil 5

Dosing Strategy

Start with standard dosing and titrate to maximum tolerated dose before declaring treatment failure. 1

• Begin tadalafil at 10mg as needed, can increase to 20mg 1
• 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 tadalafil 3
• Higher doses increase both efficacy and adverse effects 1, 2

Common Adverse Effects

• Most frequently reported: headache, flushing, nasal congestion, dyspepsia, back pain, myalgia, visual disturbances, and dizziness 1, 2, 4
• These adverse effects are generally mild to moderate and well-tolerated 1
• Avanafil has lowest rates of dyspepsia; tadalafil has lowest rates of flushing; vardenafil and avanafil have lowest rates of myalgia 4

Critical Contraindications and Safety

Never prescribe PDE5 inhibitors to patients taking nitrates—this combination causes potentially fatal hypotension. 1, 2, 4

Cardiovascular Risk Assessment

Assess cardiovascular risk before initiating ED treatment using the Princeton Consensus Panel criteria 1

High-risk patients (defer treatment until stabilized) include those with: 1, 4

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

Special Populations Requiring Caution

• Hepatic impairment: Start vardenafil at 5mg maximum 10mg in moderate impairment (Child-Pugh B); not evaluated in severe impairment (Child-Pugh C) 6
• Renal impairment: Vardenafil AUC increases 20-30% in moderate to severe renal impairment 6
• QT prolongation: Avoid vardenafil in patients with congenital QT prolongation or taking Class IA/III antiarrhythmics 6
• Alpha-blocker use: Start PDE5 inhibitors at lowest dose due to risk of symptomatic hypotension 1, 6
• Spinal cord injury: Use lower initial doses due to potential delayed metabolism 1, 4

Additional Safety Warnings

• Stop PDE5 inhibitors immediately if sudden vision loss occurs (possible NAION) 6
• Stop PDE5 inhibitors immediately if sudden hearing loss occurs 6
• Use caution in patients with anatomical penile deformation, bleeding disorders, or conditions predisposing to priapism 6

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

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
• Communicate the increased cardiovascular disease risk associated with ED to patients and primary care providers 2

Maximizing Treatment Success

Proper medication use is crucial—incorrect use accounts for a large percentage of treatment failures. 2

• Provide clear instructions on the importance of sexual stimulation for PDE5 inhibitors to work 2
• Instruct patients to take medication approximately 60 minutes before sexual activity 6
• Emphasize the need for multiple trials at maximum dose before declaring failure 1, 2
• Discuss timing relative to meals, particularly for sildenafil and vardenafil 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

• 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

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, 4
• Post-prostatectomy patients show reduced response to PDE5 inhibitors compared to the general population 1, 4
• Men with predominantly psychogenic ED should still receive PDE5 inhibitors as first-line therapy, with referral to psychotherapist as adjunct if needed 4