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Drug used in ED medications associated with small increased risk of malignant melanoma

The JAMA Network Journals

Among men in Sweden, use of erectile dysfunctions drugs with phosphodiesterase type 5 inhibitors was associated with a modest but significant increased risk of malignant melanoma, although the pattern of association raises questions about whether this association is causal, according to a study in the June 23/30 issue of JAMA.

Phosphodiesterase type 5 (PDE5; an enzyme), the target of oral erectile dysfunction (ED) drugs, is part of a pathway that has been implicated in the development of malignant melanoma. This has raised questions whether PDE5 inhibitors used to treat ED may promote malignant melanoma. An increased risk of melanoma of the skin following use of the ED drug sildenafil was recently reported in a study based on 14 cases of malignant melanoma among men taking PDE5 inhibitors. PDE5 inhibitors are the most commonly prescribed medications used for treatment of ED. Given the frequency with which these medications are used, further support for a causal association with the development of malignant melanoma would have important implications, according to background information in the article.

Stacy Loeb, M.D., M.Sc., of New York University, New York, and colleagues examined the association between use of PDE5 inhibitors and malignant melanoma risk. The study included data from the Swedish Prescribed Drug Register, the Swedish Melanoma Register, and other health care registers and demographic databases in Sweden; the researchers identified melanoma cases diagnosed from 2006 through 2012.

Of 4,065 melanoma cases, 435 men (11 percent) had filled prescriptions for PDE5 inhibitors (sildenafil, vardenafil or tadalafil), as did 1,713 men of 20,325 controls (8 percent). Analysis indicated a modest but statistically significant increased risk of melanoma in men taking PDE5 inhibitors. The most pronounced increase in risk was observed in men who had filled a single prescription, but was not significant among men with multiple filled prescriptions.

PDE5 inhibitors were significantly associated for low-stage but not for high-stage melanoma. PDE5 inhibitor use was also associated with an increased risk of basal cell carcinoma (9 percent for cases vs 8 percent for controls).

The associated increased risk was similar for short­ and long-acting PDE5 inhibitors; risk estimates were similar for sildenafil, vardenafil or tadalafil. Men taking PDE5 inhibitors had a higher educational level and annual income, factors that were also significantly associated with melanoma risk.

The authors note that overall, the pattern of association (e.g., the lack of association with multiple filled prescriptions) raises questions about whether this association is causal. "Rather, the observed association may reflect confounding [other factors that can influence outcomes] by lifestyle factors associated with both PDE5 inhibitor use and low-stage melanoma."


(doi:10.1001/jama.2015.6604; Available pre-embargo to the media at

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