Sildenafil: A Potential Risk Factor for Invasive Melanoma

Summary and Comment |
April 17, 2014

Sildenafil: A Potential Risk Factor for Invasive Melanoma

  1. Craig A. Elmets, MD

A complication to consider in treating erectile disfunction

  1. Craig A. Elmets, MD

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.


Sildenafil and other PDE5 inhibitors are widely used for erectile dysfunction. Experimental in vitro studies show that PDE5 inhibition augments tumor cell invasiveness, supporting these findings. Lack of data on dosage and duration of sildenafil use limit the analysis. Comparing the stage of melanoma in sildenafil users and the comparison population would also be of interest. The findings are not definitive, but patients who have had or are at risk for developing melanoma should be counseled about this potential adverse effect. The author of an accompanying Invited Commentary makes the excellent recommendation that patients about to be prescribed sildenafil or other PDE5 inhibitors be examined first for suspicious pigmented lesions.

Editor Disclosures at Time of Publication

  • Disclosures for Craig A. Elmets, MD at time of publication Consultant / Advisory board Astellas Pharmaceuticals Grant / research support NIH; NIH/NCI; Veteran’s Administration; Abbott Laboratories; Biogen; Clinuvel; Covan Basilea Pharmaceutica; Genentech; TenX Biopharma; University of California Editorial boards Cancer Prevention Research; Journal of the American Academy of Dermatology; Photodermatology, Photoimmunology, & Photomedicine; UpToDate Leadership positions in professional societies American Academy of Dermatology (Psoriasis Guidelines Subcommittee and Chair Designate, Clinical Guidelines and Research Committee); Photomedicine Society (Board of Directors)


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