For a male patient with erectile dysfunction (ED), Peyronie's disease, and low testosterone, which medication is more effective, sildenafil (Viagra) or tadalafil (Cialis)?

Sildenafil and Tadalafil Are Equally Effective for ED with Peyronie's and Low Testosterone

Neither sildenafil nor tadalafil demonstrates superior efficacy over the other for erectile dysfunction—the evidence shows equivalent success rates of approximately 69% versus 33% with placebo, and the choice should be based on pharmacokinetic preferences and the need to address low testosterone concurrently. 1, 2, 3

Evidence for Equivalent Efficacy

The American College of Physicians guideline explicitly states that low-quality studies comparing tadalafil and sildenafil provided insufficient evidence to determine whether one treatment was more effective than the other for successful sexual intercourse or improvement in erections. 1 This finding is reinforced by comparative data showing:

• Sildenafil achieves 69% success rate (range 52-85%) versus placebo 35.5% 3
• Tadalafil achieves 69% success rate (range 50-85%) versus placebo 33% 3
• Both agents improve erections in 73-88% of patients compared to 26-32% with placebo 3

Very-low-quality evidence showed that adverse events did not statistically significantly differ among men receiving sildenafil, tadalafil, and vardenafil. 1

Critical Consideration: Low Testosterone Requires Combination Therapy

For men with testosterone deficiency and ED, combining either PDE5 inhibitor with testosterone therapy is more effective than PDE5 inhibitor monotherapy. 1, 2 The American College of Physicians found that low-quality evidence was insufficient to determine whether testosterone plus sildenafil was more effective than sildenafil and placebo alone, but clinical practice suggests combination therapy addresses both the vascular and hormonal components of ED. 1

Key points about testosterone deficiency:

• Men with testosterone deficiency respond less robustly to PDE5 inhibitors alone 2, 4
• Testosterone therapy alone is not effective monotherapy for ED 2
• Check total testosterone, free testosterone, and SHBG levels before declaring PDE5 inhibitor failure 2

Peyronie's Disease Considerations

Neither guideline nor research evidence specifically addresses differential efficacy of sildenafil versus tadalafil in Peyronie's disease. Both PDE5 inhibitors work by the same mechanism—enhancing nitric oxide-mediated vasodilation in penile arteries—and would be expected to have similar efficacy in this population. 2 The presence of Peyronie's disease does not favor one agent over the other based on available evidence.

Choosing Between Sildenafil and Tadalafil

Since efficacy is equivalent, selection should be based on pharmacokinetic differences:

Choose Tadalafil When:

• The patient values sexual spontaneity and does not want to time medication (effective up to 36 hours) 2, 3
• Coexisting benign prostatic hyperplasia is present (tadalafil 5 mg daily treats both BPH and ED simultaneously, FDA-approved indication) 2
• Daily dosing is preferred to eliminate timing concerns entirely (tadalafil 2.5-5 mg once daily) 2

Choose Sildenafil When:

• The patient prefers scheduled sexual activity with a more predictable 4-5 hour window of action 2, 3
• There is concern about potential need for emergency nitrates (shorter 24-hour washout period versus 48 hours for tadalafil) 2, 3
• Dose titration is desired (sildenafil shows dose-related improvement from 25 mg to 50 mg, though less additional benefit from 50 mg to 100 mg) 1, 3, 4

Dose-Response Relationships

Sildenafil demonstrates dose-dependent efficacy (50 mg more effective than 25 mg), while tadalafil does NOT show dose-dependent improvement between 5 mg, 10 mg, and 20 mg doses. 1, 2, 3 For tadalafil, the choice between 10 mg and 20 mg should be based primarily on tolerability rather than expecting dramatically better efficacy at higher doses. 2

Ensuring an Adequate Trial Before Declaring Failure

Before declaring treatment failure with either agent, patients must complete at least 5 separate attempts at maximum tolerated dose with proper technique. 2, 3, 4 Many apparent failures are due to:

• Inadequate sexual stimulation (PDE5 inhibitors require sexual arousal to work) 2
• Heavy alcohol use (impairs erectile function independent of medication) 2
• Taking medication with large or fatty meals (reduces efficacy) 2
• Unaddressed hormonal abnormalities (testosterone deficiency limits response) 2, 4
• Relationship issues with partner (psychological factors significantly impact response) 2

Safety Profile

Both agents share the same critical safety warnings:

• Absolute contraindication with any form of nitrate medication due to life-threatening hypotension risk 1, 2, 3, 4
• Common adverse effects include headache, flushing, rhinitis, dyspepsia, with serious adverse events occurring in <2% of patients 1, 2
• Tadalafil has lower rates of flushing but higher rates of back pain and myalgia compared to sildenafil 2

Practical Algorithm for This Patient

1. Screen for absolute contraindications (nitrate use in any form) 2, 3
2. Assess cardiovascular fitness (can the patient walk 1 mile in 20 minutes or climb 2 flights of stairs without symptoms?) 2
3. Confirm testosterone deficiency with laboratory testing (total testosterone, free testosterone, SHBG) 2
4. Initiate combination therapy: PDE5 inhibitor PLUS testosterone replacement 1, 2
5. Choose PDE5 inhibitor based on patient preference for spontaneity versus scheduled activity:
   • Tadalafil 10 mg as needed (or 5 mg daily if BPH coexists) for spontaneity 2
   • Sildenafil 50 mg as needed for scheduled activity 3, 4
6. Ensure adequate trial: minimum 5 attempts at maximum tolerated dose with proper technique 2, 3, 4
7. If suboptimal response, verify adequate sexual stimulation, proper timing, absence of heavy alcohol, and no large meals before dose escalation 2
8. If failure with first PDE5 inhibitor, switch to the other before proceeding to second-line therapies 2