Sildenafil, the most common drug prescribed for male impotence, 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.

Li W-Q et al. JAMA Intern Med 2014 Apr 7. Robinson JK. JAMA Intern Med 2014 Apr 7.
A complication to consider in treating erectile disfunction