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

Treatment Options for Erectile Dysfunction

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

First-Line Therapy: PDE5 Inhibitors

Initial Prescription

• Start with an FDA-approved oral PDE5 inhibitor (sildenafil 50mg, tadalafil 10mg, or vardenafil 10mg) as initial therapy 1, 2
• Provide explicit instructions: take sildenafil or vardenafil approximately 60 minutes before sexual activity; tadalafil can be taken 30 minutes to 12 hours before 3, 4
• Sexual stimulation is required for these medications to work—they do not cause automatic erections 3, 4
• Maximum dosing frequency is once daily 1, 3

Dose Optimization

• Titrate to maximum tolerated dose before declaring treatment failure 1, 2
• For sildenafil: increase from 50mg to 100mg if needed (25mg for elderly or those with hepatic/renal impairment) 1
• For vardenafil: increase from 10mg to 20mg if needed (5mg starting dose for moderate hepatic impairment, maximum 10mg) 4
• For tadalafil: increase from 10mg to 20mg if needed 1, 3
• Trial at least 5 separate occasions at maximum tolerated dose before considering treatment failure 2

Absolute Contraindications

• Concurrent nitrate use (nitroglycerin, isosorbide dinitrate/mononitrate) or recreational "poppers" (amyl/butyl nitrite)—can cause life-threatening hypotension 1, 3, 4
• Guanylate cyclase stimulators (riociguat) 3
• Unstable angina, uncontrolled hypertension, recent MI/stroke (within 6 months), severe heart failure, or high-risk arrhythmias 2
• Congenital QT prolongation or Class IA/III antiarrhythmics for vardenafil 4

Relative Cautions

• Alpha-blocker use: start PDE5 inhibitor at lowest dose due to additive hypotensive effects 4
• Moderate hepatic impairment: reduce starting doses 4
• History of NAION (non-arteritic anterior ischemic optic neuropathy) in one eye increases risk in the other eye 4

Second-Line Therapies

After documented PDE5 inhibitor failure at maximum dose over at least 5 attempts, proceed to second-line options: 1, 2

• Intraurethral alprostadil suppositories (MUSE): insert into urethra 5-10 minutes before intercourse 1, 5
• Intracavernosal injection therapy: alprostadil, papaverine, or combination therapy injected directly into corpus cavernosum 1, 5
• Vacuum constriction devices: mechanical devices that draw blood into penis, with constriction ring to maintain erection 1

These second-line therapies have high efficacy but significant attrition rates due to invasiveness 5

Third-Line Therapy

Penile prosthesis implantation is the definitive treatment for refractory ED unresponsive to all other therapies. 1, 2

Adjunctive and Combination Therapies

Testosterone Replacement

• Measure serum total testosterone in all men with ED, particularly those with decreased libido 1, 2
• If total testosterone <300 ng/dL with symptoms, consider testosterone replacement as monotherapy or combined with PDE5 inhibitors 1, 2
• Low-quality evidence suggests combination therapy (testosterone plus PDE5 inhibitor) may be more effective than PDE5 inhibitor alone in hypogonadal men, though data are insufficient to make definitive recommendations 1

Combination with Other Therapies

• PDE5 inhibitors combined with psychotherapy, lifestyle modifications, or cardiovascular medications (statins, ACE inhibitors) show greater improvements than PDE5 inhibitors alone 1
• However, avoid combining multiple ED-specific treatments (e.g., PDE5 inhibitor plus intracavernosal injection) without specialist guidance 1

Psychosexual Counseling

• For men with predominantly psychogenic ED (evidenced by preserved nocturnal/morning erections), offer referral to psychotherapist as alternative or adjunct to medical treatment 1
• Psychotherapy helps patients and partners improve communication, reduce performance anxiety, and integrate ED treatments into sexual relationships 1

Critical Cardiovascular Considerations

ED is a risk marker for cardiovascular disease as strong as smoking or family history of MI—use the diagnosis as an opportunity for cardiovascular risk assessment. 1, 2

• Screen all ED patients for cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking) 1, 2
• Consider exercise stress testing in men with known/suspected coronary artery disease before prescribing ED treatment 1, 6
• Communicate cardiovascular risk to patient, partner, and primary care provider for appropriate referrals 1
• Defer sexual activity in high-risk cardiac patients until condition is stabilized 1

Investigational Therapies NOT Recommended

Low-intensity shockwave therapy (LiSWT) is not recommended as first-line treatment—it lacks FDA approval and guideline support. 2

• May only be considered as investigational option after documented PDE5 inhibitor failure, patient refusal of second-line therapies, and explicit patient understanding of lack of approval 2
• Do not promise permanent results—evidence shows declining efficacy after 2 years 2

Common Pitfalls to Avoid

• Never prescribe PDE5 inhibitors without screening for nitrate use—this combination can be fatal 1, 3, 6
• Do not declare treatment failure after only 1-2 attempts—require at least 5 attempts at maximum tolerated dose 2
• Do not ignore cardiovascular screening—ED often precedes cardiovascular events by 2-5 years 1, 2
• Do not overlook testosterone deficiency in men with low libido—measure testosterone in all ED patients 1, 2
• Do not forget that tadalafil remains active for >2 days—important for emergency cardiac care 3