Can alprostadil (prostaglandin E1) cause fibrosis on penile tissue in adult males with erectile dysfunction (ED)?

Alprostadil and Penile Fibrosis Risk

Alprostadil can cause penile fibrosis, but the risk varies significantly by route of administration: intracavernosal injection carries a 2-23% risk of fibrosis, while intraurethral alprostadil has no documented cases of fibrosis in clinical trials. 1, 2, 3

Risk Stratification by Route of Administration

Intracavernosal Alprostadil (Highest Risk)

• Penile fibrosis occurs in 2-23% of patients using intracavernosal alprostadil injections, with the wide range reflecting differences in study methodology, duration of follow-up, and systematic examination protocols. 2, 3
• The most rigorous prospective study found penile fibrosis in 23.3% of 245 patients after an average of 29 months of self-injection therapy (mean 142 injections total). 2
• FDA-approved clinical trials reported lower rates of 2% penile fibrotic complications during 6-month follow-up, though this likely underestimates long-term risk due to shorter observation periods. 3
• The UK guidelines acknowledge penile fibrosis as a recognized complication of intracavernosal injection with reported incidence ranging from <1% to more than 20%. 4

Intraurethral Alprostadil (Minimal to No Risk)

• Intraurethral alprostadil (MUSE) has demonstrated no occurrences of fibrosis in key clinical studies, distinguishing it from intracavernosal injection. 1
• The 2018 AUA Erectile Dysfunction Guideline recommends intraurethral alprostadil as an alternative option but does not list fibrosis among its adverse effects. 4
• While long-term fibrosis risk cannot be definitively excluded, systematic reviews through 2019 confirm intraurethral alprostadil does not share the fibrosis risk profile of intracavernosal administration. 1, 5

Mechanism and Risk Factors

Why Intracavernosal Injection Causes Fibrosis

• Repeated mechanical trauma from needle insertion combined with local tissue reaction to alprostadil creates cumulative injury to the tunica albuginea and corpus cavernosum. 2
• Risk correlates with total number of injections (mean 142 injections in patients who developed fibrosis) and cumulative alprostadil dose (mean 1703 micrograms total). 2
• Frequency of injection matters: patients injecting 5.2 times per month over 29 months showed 23.3% fibrosis rate. 2

Critical Distinction from Priapism-Related Fibrosis

• The AUA/SMSNA guidelines emphasize that corporal fibrosis leading to penile shortening results from untreated ischemic priapism (>36 hours), not from alprostadil itself. 4
• Alprostadil alone is actually less prone to cause ischemic priapism compared to papaverine and phentolamine combinations, which counteract normal detumescence pathways. 4
• Priapism occurs in only 1% of patients using intracavernosal alprostadil, and prolonged erections in 5%. 3

Clinical Monitoring Requirements

Mandatory Pre-Treatment and Follow-Up Examination

• Examine patients methodically for pre-existing fibrotic changes before initiating intracavernosal therapy and at regular subsequent reviews. 2
• 30 of 300 patients (10%) in one series had pre-existing fibrotic changes that would have been incorrectly attributed to alprostadil without baseline examination. 2

Patient Counseling Obligations

• Specifically warn patients about the possibility of penile fibrosis before starting intracavernosal alprostadil. 2
• Instruct patients on penile self-examination techniques to detect early fibrotic changes (plaques, curvature, deformity). 2
• The AUA guidelines require in-office test doses with detailed counseling regarding adverse effects before prescribing either intracavernosal or intraurethral alprostadil. 4, 6

Common Pitfalls to Avoid

• Do not assume intraurethral and intracavernosal alprostadil carry equivalent fibrosis risk—they have fundamentally different safety profiles. 1
• Never skip baseline penile examination before starting intracavernosal therapy, as pre-existing Peyronie's disease or fibrosis may be incorrectly attributed to treatment. 2
• Do not rely solely on patient-reported symptoms—systematic physical examination detects fibrosis that patients may not spontaneously report. 2
• Recognize that older literature reporting <1% fibrosis rates likely reflects inadequate systematic examination and short follow-up rather than true incidence. 4, 2