What is the recommended treatment approach for erectile dysfunction (ED)?

Treatment of Erectile Dysfunction

PDE5 inhibitors (sildenafil, vardenafil, tadalafil, avanafil) are the first-line pharmacologic treatment for erectile dysfunction, with proven efficacy showing 69% success rates compared to 35% with placebo. 1, 2, 3

Initial Assessment and Risk Stratification

Before prescribing any ED treatment, obtain the following:

• Glucose-lipid profile to assess metabolic risk factors 1
• Morning total testosterone level (if not checked in the last 12 months) 1
• Cardiovascular risk assessment including blood pressure, waist circumference/BMI, lipid panel, fasting glucose or HbA1c 2, 4

Testosterone testing is specifically indicated when patients present with decreased libido, reduced sexual satisfaction, or other hypogonadal symptoms - not routinely for all ED patients. 1, 2

First-Line Treatment: PDE5 Inhibitors

Drug Selection

All four PDE5 inhibitors have equivalent efficacy in the general ED population. 1, 4 Choose based on pharmacokinetics and patient lifestyle preferences:

• Tadalafil (10-20 mg): 17.5-hour half-life providing a 36-hour window; ideal for spontaneity and has lower flushing rates 1, 4, 3
• Sildenafil (50-100 mg): Shorter duration, taken 30-60 minutes before activity 1, 2
• Vardenafil (10-20 mg): Available as tablets and orally disintegrating tablets 1
• Avanafil (50-200 mg): Rapid onset option 1

Dosing Strategy

Start with standard dosing and titrate to maximum dose before declaring treatment failure. 2, 4 An adequate trial requires at least 5 separate occasions at the maximum dose before considering the medication ineffective. 2, 4

For tadalafil specifically: begin at 10 mg as needed, increase to 20 mg if needed. 4, 3 Daily tadalafil 5 mg is an alternative for men desiring continuous readiness. 3

Critical Contraindications

Never prescribe PDE5 inhibitors to patients taking nitrates in any form - this combination causes potentially fatal hypotension. 1, 2, 4, 3 This is an absolute contraindication.

Defer treatment in high-risk cardiac patients until stabilized, including those with:

• Unstable or refractory angina
• Uncontrolled hypertension
• NYHA class II or greater heart failure
• MI or stroke within previous 2 weeks
• High-risk arrhythmias
• Hypertrophic obstructive cardiomyopathy
• Moderate-to-severe valvular disease 2, 4

Dose Adjustments

Renal impairment:

• CrCl 30-50 mL/min: Start tadalafil 5 mg, maximum 10 mg every 48 hours 3
• CrCl <30 mL/min or hemodialysis: Maximum tadalafil 5 mg every 72 hours 3

Hepatic impairment:

• Mild-moderate (Child-Pugh A or B): Maximum tadalafil 10 mg once daily 3
• Severe (Child-Pugh C): PDE5 inhibitors not recommended 3

CYP3A4 inhibitors (ketoconazole, ritonavir):

• As-needed dosing: Maximum tadalafil 10 mg every 72 hours 3
• Daily dosing: Maximum tadalafil 2.5 mg 3

Optimizing PDE5 Inhibitor Response

Before switching medications or declaring treatment failure, verify:

• Correct dosing and timing relative to sexual activity 1, 4
• Adequate sexual stimulation is occurring 1
• No food or drug interactions interfering 4
• No heavy alcohol use 4
• Relationship issues are not the primary barrier 4

For PDE5 inhibitor non-responders with low testosterone, adding testosterone therapy may restore effectiveness in hypogonadal men experiencing reduced libido and satisfaction. 1, 2 However, testosterone therapy is not indicated in men with normal testosterone levels. 1

Combination and Adjunctive Therapies

Combination approaches show enhanced results in PDE5 inhibitor non-responders:

• Low-intensity shockwave therapy (LI-SWT) plus daily tadalafil or vacuum erection devices demonstrated superior outcomes compared to monotherapy 1
• Antioxidants combined with PDE5 inhibitors may be considered for complex cases 1

Psychosocial interventions including sexual skills training and cognitive behavioral therapy complement medical ED treatment effectively, whether delivered individually or online. 1

Second-Line Therapies

When PDE5 inhibitors fail after adequate trial, proceed to:

Intracavernous Injection Therapy

Vasoactive drug injection remains available at any stage of treatment planning and shows mean IIEF-EF improvement of 3.21 points versus placebo. 1 Available compounds include alprostadil, papaverine, phentolamine, and combination therapies. 1

Botulinum neurotoxin A (BoNT-A) shows promise in PDE5 inhibitor non-responders, with up to 40% of patients resuming satisfactory sexual activity with only mild local side effects. 1

Low-Intensity Shockwave Therapy (LI-SWT)

LI-SWT is the only currently marketed treatment potentially offering a cure for ED rather than temporary symptom relief. 1, 5

• Mean IIEF-EF improvement of approximately 4 points in pooled RCT data 1
• Effects detectable up to 5 years in some cases 1
• Current EAU guidelines recommend LI-SWT may be used in men with mild vasculogenic ED (weak recommendation) 1
• Particularly beneficial in PDE5 inhibitor non-responders 1

However, the benefit is still under evaluation, standardized treatment protocols are lacking, and evidence from randomized trials remains conflicting. 1, 5

Vacuum Erection Devices (VEDs)

VEDs show 90% initial efficacy, dropping to 50-64% after 2 years. 1 Side effects include pain and bruising. 1 These are particularly beneficial in older patients undertaking infrequent intercourse but are contraindicated with bleeding disorders. 1

Third-Line Therapy: Surgical Management

Penile prosthesis implantation (PPI) is the definitive intervention for patients unsuitable for or unresponsive to other treatments. 1, 2, 4

• Three-piece inflatable devices provide more natural erections 1
• Semirigid prostheses offer simpler implantation and use 1

Post-traumatic arteriogenic ED can be treated with surgical revascularization in young patients with 60-70% success rates. 1 However, venous ligation is no longer recommended due to poor outcomes. 1

Lifestyle Modifications (Essential for All Patients)

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

• Smoking cessation
• Weight loss if overweight
• Increasing physical activity
• Avoiding excess alcohol consumption
• Optimal management of diabetes, hypertension, and dyslipidemia 2, 4

Treatments NOT Recommended

The following lack sufficient evidence and should not be used:

• Yohimbine - not recommended based on insufficient efficacy data 1
• Trazodone - pooled results not statistically significant versus placebo 1
• Herbal therapies (except possibly Korean red ginseng, which needs larger validation trials) - lack regulation, inconsistent potency, and some contaminated with undisclosed PDE5 inhibitors 1
• Topical therapies - no significant efficacy beyond intraurethral alprostadil 1
• Testosterone in men with normal testosterone levels - not indicated for ED treatment 1

Investigational Therapies

The following show promise but require further validation:

• Platelet-rich plasma (PRP) - protocol variations limit evidence strength; restricted to clinical trials 1
• Stem cell therapy - 18 phase 1/2 trials with 373 patients confirmed safety but lack sufficient efficacy data for clinical recommendation 1