What are the treatment options for erectile dysfunction?

Treatment of Erectile Dysfunction

First-Line Treatment: Oral PDE5 Inhibitors

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

Efficacy and Selection

• All three FDA-approved PDE5 inhibitors demonstrate similar efficacy in the general ED population, with success rates of 69% compared to 35% with placebo 1
• Choose between PDE5 inhibitors based on pharmacokinetic differences and patient lifestyle preferences rather than efficacy, since all three work equally well 1
• Tadalafil offers a significantly longer half-life (17.5 hours) providing a 36-hour window of opportunity, making it ideal for men who prefer spontaneity 1, 2
• Tadalafil has lower rates of flushing compared to other PDE5 inhibitors 1, 2
• Sildenafil and vardenafil have half-lives of approximately 4 hours 3

Dosing Strategy

• Start with standard dosing: tadalafil 10mg as needed, sildenafil 50mg, or vardenafil 10mg 1
• Titrate to maximum tolerated dose before declaring treatment failure 1
• An adequate trial requires at least 5 separate occasions at the maximum dose before considering the medication ineffective 1, 4
• For sildenafil, improvement is dose-related (50mg vs 25mg but not 100mg vs 50mg); for vardenafil, improvement is dose-related (20mg vs 10mg vs 5mg); for tadalafil, improvement is NOT dose-dependent between 5-20mg 5, 4
• Daily tadalafil 2.5-5mg once daily eliminates the need to time medication with sexual activity for couples preferring spontaneous rather than scheduled sexual activity 4

Critical Safety Contraindications

• Never prescribe PDE5 inhibitors to patients taking nitrates—this combination causes potentially fatal hypotension 1, 2, 4
• Wait at least 24 hours after sildenafil or vardenafil before administering nitrates; wait at least 48 hours after tadalafil 2
• Assess cardiovascular risk before initiating treatment: patients unable to walk 1 mile in 20 minutes or climb 2 flights of stairs in 20 seconds without symptoms require cardiology referral 2
• High-risk patients requiring deferral until stabilized include those with 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, and moderate-to-severe valvular disease 1
• Avoid vardenafil in patients with congenital QT prolongation or those taking Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmic medications 6

Common Adverse Effects

• Most common side effects include headache, flushing, nasal congestion, dyspepsia, back pain, and myalgia 1, 2
• Serious adverse events occur in less than 2% of patients, with no significant difference between PDE5 inhibitors and placebo 5, 2
• These medications are relatively well-tolerated with mild to moderate adverse events 1

Special Dosing Considerations

• For moderate hepatic impairment (Child-Pugh B), start vardenafil at 5mg with maximum dose of 10mg 6
• Vardenafil has not been evaluated in severe hepatic impairment (Child-Pugh C) 6
• For moderate to severe renal impairment, vardenafil AUC increases 20-30% 6

Optimizing Treatment Response

Before Declaring Treatment Failure

• Evaluate modifiable factors: hormonal abnormalities, food or drug interactions, timing and frequency of dosing, adequacy of sexual stimulation, heavy alcohol use, and relationship issues with partner 1, 4
• Sexual stimulation is necessary for PDE5 inhibitors to be effective—incorrect use accounts for a large percentage of treatment failures 4
• Many perceived failures are due to inadequate trials, improper timing, or lack of sexual stimulation 4
• After re-education on proper use and dose optimization, many initial non-responders become responders 2

Hormonal Testing

• Do not routinely measure testosterone in all ED patients—individualize based on clinical presentation 1
• Measure testosterone levels when patients present with decreased libido, premature ejaculation, fatigue, testicular atrophy, or muscle atrophy 1
• Consider measuring free testosterone in patients who do not respond to PDE5 inhibitors 1
• Patients with morning total testosterone <300 ng/dL may benefit from combination therapy with testosterone replacement 2

Combination Therapy with Testosterone

• For men with ED and testosterone deficiency (testosterone <300 ng/dL), combining a PDE5 inhibitor with testosterone therapy is more effective than PDE5 inhibitor alone 2, 4
• Testosterone therapy alone is not an effective monotherapy for ED 4
• Low-quality evidence was insufficient to definitively determine whether testosterone plus sildenafil was more effective than sildenafil alone 5

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, and optimal management of diabetes, hypertension, and dyslipidemia 1, 2

Second-Line Therapies

• If PDE5 inhibitors fail after adequate trial (at least 5 attempts at maximum dose), proceed to second-line interventions 1
• Second-line options include intraurethral alprostadil suppositories, intracavernous vasoactive drug injection, or vacuum constriction devices 1
• Intracavernous alprostadil (edex®) is indicated for erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology 7
• Alprostadil should produce an erection in 5-20 minutes lasting up to one hour 7
• Use alprostadil no more than 3 times per week with at least 24 hours between injections 7
• Combination therapy with topical alprostadil and PDE5 inhibitor appears more effective than topical alprostadil alone in patients who failed PDE5 inhibitor monotherapy 8

Contraindications to Alprostadil

• Men with conditions that might result in long-lasting erections (sickle cell anemia or trait, leukemia, multiple myeloma) should not use alprostadil 7
• Men with penile implants, severe penile curvature, or those advised not to engage in sexual activity should not use alprostadil 7
• Erections lasting more than 6 hours require immediate medical attention to prevent permanent impotence 7

Third-Line Therapy

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

Special Populations

• 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 spinal cord injury require lower initial doses due to potential delayed metabolism 1

Ongoing Management

• Periodically assess efficacy, side effects, and any significant changes in health status or medications 2, 4
• Verify that cardiovascular health hasn't changed, review new medications, assess treatment effectiveness, and evaluate side effects 4