What are the first-line treatments for erectile dysfunction (ED)?

First-Line Treatment for Erectile Dysfunction

Oral PDE5 inhibitors (sildenafil, tadalafil, or vardenafil) are the first-line treatment for erectile dysfunction unless contraindicated, with proven efficacy showing 69% success rates compared to 35% with placebo. 1, 2

Initial Pharmacologic Management

PDE5 Inhibitors as Standard First-Line Therapy

• All three FDA-approved PDE5 inhibitors (sildenafil, tadalafil, vardenafil) have equivalent efficacy in the general ED population, so selection should be based on pharmacokinetic differences and patient lifestyle preferences rather than effectiveness 1, 3

• These medications demonstrate statistically significant and clinically relevant improvements in erectile function across all patient categories 1

• Common adverse effects include headache, flushing, nasal congestion, dyspepsia, back pain, and myalgia, but these are typically mild to moderate and well-tolerated 1, 4

Choosing the Right PDE5 Inhibitor

• 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 over planned sexual activity 1, 4

• Tadalafil has lower rates of flushing compared to sildenafil and vardenafil 1, 4

• Sildenafil and vardenafil have approximately 4-hour half-lives and faster onset of action in some patients 5

• Food (especially fatty meals) affects absorption of sildenafil and vardenafil but not tadalafil 5

Proper Dosing Strategy

• Start tadalafil at 10mg as needed, with option to increase to 20mg based on response and tolerability 1, 4

• An adequate trial requires at least 5 separate occasions at the maximum tolerated dose before declaring treatment failure 1, 2

• Dose titration to maximum tolerated dose is strongly recommended because it significantly increases efficacy and patient satisfaction 3

• Higher doses provide greater efficacy but also increased risk of adverse effects 1

Critical Safety Screening Before Prescribing

Absolute Contraindications

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

• Wait at least 24 hours after sildenafil or vardenafil before administering nitrates 4

• Wait at least 48 hours after tadalafil before administering nitrates 4

High-Risk Cardiovascular Patients (Defer Treatment Until Stabilized)

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

Functional Cardiac Screening

• Patients who cannot walk 1 mile in 20 minutes or climb 2 flights of stairs in 20 seconds without symptoms require cardiology referral before ED treatment 4

Optimizing Treatment Success

Common Reasons for Apparent Treatment Failure

• Many perceived PDE5 inhibitor failures are due to modifiable factors including lack of adequate sexual stimulation, incorrect timing of medication, inadequate dosing, and undiagnosed hormonal abnormalities 4

• After re-education on proper use and dose optimization, many initial non-responders become responders 4

• Patients must understand that sexual stimulation is required for PDE5 inhibitors to work 4

Hormonal Evaluation

• 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

• Patients with morning total testosterone <300 ng/dL may benefit from combination therapy with testosterone replacement, which can be more effective than PDE5 inhibitors alone 4

Lifestyle Modifications (Essential Adjunct)

• Counsel all ED patients on risk factor modification regardless of pharmacologic treatment 1, 4

• Recommend smoking cessation, weight loss if overweight, increasing physical activity, and avoiding excess alcohol consumption 1, 4

• Optimize management of diabetes, hypertension, and dyslipidemia 1, 4

• ED is often the first manifestation of cardiovascular disease, making cardiovascular risk factor screening essential 2

Stepwise Progression When First-Line Fails

Second-Line Therapies

• After documented failure of maximum-dose PDE5 inhibitor trial (at least 5 attempts), proceed to second-line interventions including intraurethral alprostadil suppositories, intracavernous vasoactive drug injection, or vacuum constriction devices 6, 1, 2

Third-Line Therapy

• Penile prosthesis implantation is the definitive third-line intervention for refractory ED 6, 1, 2

Special Population Considerations

• Men with diabetes have more severe ED at baseline and respond less robustly to PDE5 inhibitors, though these medications remain effective 1, 7

• Post-prostatectomy patients show reduced response to PDE5 inhibitors compared to the general population but still achieve clinically meaningful improvements 1, 7

• Treatment should be applied in a stepwise fashion with increasing invasiveness and risk balanced against likelihood of efficacy 6