Sildenafil: A Potential Risk Factor for Invasive Melanoma

Sildenafil, the most common drug prescribed for male erectile dysfunction, with over $2 billion in annual sales, acts by inhibiting phosphodiesterase 5 (PDE5). BRAF mutations are associated with approximately 50% of melanomas, and recent studies show that the B-Raf protein also inhibits PDE5. To examine whether sildenafil increases risk for invasive melanoma, investigators accessed data on 25,848 participants, 5.3% of whom had taken sildenafil within the previous 3 months and 6.3% of whom had ever taken it. Those with previously diagnosed malignancies, including melanomas and nonmelanoma skin cancers, were excluded.

Between 2000 and 2010, 142 invasive melanomas were diagnosed in these participants. After multivariate-adjusted analysis controlling for family melanoma history, sun exposure, and ultraviolet index in the state of residence, melanomas were significantly more likely to have occurred in recent sildenafil users (hazard ratio, 1.84; confidence interval, 1.04-3.22) and sildenafil ever-users (HR, 1.92; CI, 1.14-3.22). There was no association between sildenafil and cutaneous squamous cell carcinomas or basal cell carcinomas. Erectile dysfunction per se was not a risk factor — participants with erectile dysfunction but no sildenafil use had no increased risk.