What is the first-line treatment for erectile dysfunction (ED)?

First-Line Treatment for Erectile Dysfunction

Oral phosphodiesterase type 5 (PDE5) inhibitors should be offered as the first-line treatment for erectile dysfunction unless contraindicated. 1

Assessment Before Treatment

Before initiating treatment, consider:

• Cardiovascular risk assessment: Categorize patients into low, intermediate, or high cardiovascular risk 1

  • High-risk patients: Unstable/refractory angina, uncontrolled hypertension, recent MI/stroke (within 2 weeks), severe heart failure, high-risk arrhythmias, or moderate-to-severe valvular disease
  • Low-risk patients: Can receive any first-line therapy
  • Intermediate-risk patients: Should undergo cardiologist evaluation first

• Medication review: Check for contraindications, particularly nitrates 1, 2, 3

  • Absolute contraindication: Concurrent use of nitrates (risk of severe hypotension)
  • Caution with alpha-blockers: Start with lowest PDE5 inhibitor dose

PDE5 Inhibitors as First-Line Treatment

Efficacy

All available PDE5 inhibitors show similar effectiveness:

• High-quality evidence shows significant improvement in successful sexual intercourse attempts 1:
  • Sildenafil: 69% success vs. 35.5% with placebo
  • Vardenafil: 68% success vs. 35% with placebo
  • Tadalafil: 69% success vs. 33% with placebo

Available Options

1. Sildenafil (Viagra)

   • Onset: Effects within 14 minutes in some patients 4
   • Duration: ~4-hour half-life 4
   • Food interaction: Absorption reduced with fatty meals 4
   • Dosing: 25mg, 50mg, 100mg as needed

2. Vardenafil (Levitra)

   • Onset: Effects within 10 minutes in some patients 4
   • Duration: ~4-hour half-life 4
   • Food interaction: Absorption reduced with fatty meals 4
   • Dosing: 5mg, 10mg, 20mg as needed

3. Tadalafil (Cialis)

   • Onset: Effects within 16 minutes in some patients 4
   • Duration: Extended 17.5-hour half-life 4
   • Food interaction: Minimal effect of food on absorption 4
   • Dosing: 2.5mg, 5mg daily or 10mg, 20mg as needed 2

4. Newer agents (less established in guidelines):

   • Avanafil: Faster onset, enhanced selectivity 5
   • Udenafil and Mirodenafil: Similar efficacy to established agents 1

Special Populations

• Diabetes: All PDE5 inhibitors are effective but may have lower response rates compared to non-diabetic men 1

• Cardiovascular disease: PDE5 inhibitors are effective and safe in stable cardiovascular disease 1

• Post-prostatectomy: PDE5 inhibitors are effective in men after nerve-sparing radical prostatectomy 1

• Hepatic impairment: Dose adjustment required (e.g., start with lower doses of vardenafil in moderate impairment) 3

• Renal impairment: PDE5 inhibitors generally safe with dose adjustments for severe impairment 3

Common Pitfalls and Considerations

• Inadequate dosing: Higher doses may be needed for optimal efficacy, particularly in difficult-to-treat populations 1

• Improper use: Patients should be informed that sexual stimulation is required for PDE5 inhibitors to work 3

• Premature discontinuation: Many patients discontinue therapy without adequate trials or dose optimization 6

• Drug interactions: Beyond nitrates, be cautious with alpha-blockers, certain antiarrhythmics, and medications that prolong QT interval 3

• Hormonal evaluation: Routine hormonal testing (testosterone, prolactin) is not clearly supported by evidence but may be considered in selected cases 1

Treatment Algorithm

1. First attempt: Start with any PDE5 inhibitor based on:

   • Patient preference regarding onset and duration
   • Anticipated frequency of sexual activity (daily tadalafil for frequent activity)
   • Presence of comorbidities requiring dose adjustment

2. If inadequate response:

   • Ensure proper use (timing, sexual stimulation)
   • Optimize dose before switching agents
   • Consider alternative PDE5 inhibitor if no response after dose optimization

3. If PDE5 inhibitors fail or are contraindicated:

   • Consider second-line options: intracavernosal injections or intraurethral suppositories 1
   • Consider vacuum constriction devices 1

PDE5 inhibitors have revolutionized ED treatment with high efficacy, favorable safety profiles, and convenience, making them the clear first-line option for most men with erectile dysfunction.