Erectile dysfunction drugs associated with small increased risk of malignant melanoma

Erectile dysfunction (ED) drugs made with phosphodiesterase type 5 inhibitors were associated with a modest but significant increased risk of malignant melanoma, according to a study of men in Sweden published in the June 23/30 issue of the Journal of the American Medical Association. However, the authors questioned whether this association was causal or was confounded by lifestyle factors.

The enzyme phosphodiesterase type 5 (PDE5) is the target of oral ED drugs. It is also part of a pathway that has been implicated in the development of malignant melanoma, raising questions as to 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.

In the current study, Stacy Loeb, MD, MSc, of New York University, New York, and colleagues examined the association between use of PDE5 inhibitors and malignant melanoma risk. They 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%) had filled prescriptions for PDE5 inhibitors (sildenafil, vardenafil, or tadalafil), as did 1,713 men of 20,325 controls (8%). Analysis indicated a modest but statistically significant increased risk of melanoma in men taking PDE5 inhibitors. However, men with multiple filled prescriptions did not have a greater risk than those with a single prescription.

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

“Overall, the pattern of association raises questions about whether this association is causal. Rather, the observed association may reflect confounding by lifestyle factors associated with both PDE5 inhibitor use and low-stage melanoma,” the authors concluded.