Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction Associated With Risk of Melanoma
In a study in Swedish men reported in JAMA, Loeb et al found a statistically significant increase in risk of malignant melanoma in those using oral phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction. However, risk was not significantly elevated in men filling multiple PDE5 inhibitor prescriptions. The target of these drugs is part of the RAS-RAF-MEK-ERK signaling pathway involved in the development of melanoma.
Study Details
The nationwide population-based, nested case-control study involved data from the Swedish Prescribed Drug Register, Swedish Melanoma Register, and other Swedish health-care registers and demographic databases. The study included 4,065 melanoma cases diagnosed between 2006 and 2012 and 5 randomly selected controls per case matched for year of birth. Analysis of PDE5 inhibitor use was according to use of sildenafil or use of vardenafil or tadalafil (Cialis).
Risk
In total, 435 men with melanoma (11%) had filled prescriptions for PDE5 inhibitors; of these, 275 (63%) had filled prescriptions for sildenafil and 224 (51%) had filled prescriptions for vardenafil or tadalafil. Among 20,325 controls, 1,713 (8%) had filled prescriptions for PDE5 inhibitors. In multivariate analysis, use of PDE5 inhibitors was associated with increased risk for melanoma (odds ratio [OR] =1.21, 95% confidence interval [CI] = 1.08–1.36). Risk was significantly increased among men who had filled a single prescription (4% for cases vs 3% for controls, OR = 1.32, 95% CI = 1.10–1.59), but was nonsignificantly increased among those who filled two to five prescriptions (4% vs 3%, OR = 1.14, 95% CI = 0.95–1.37) or among those who filled six or more prescriptions (3% vs 2%, OR = 1.17, 95% CI = 0.95–1.44). Risk estimates were similar for sildenafil use and vardenafil or tadalafil use.
PDE5 inhibitor use was significantly associated with melanoma stage 0 (OR = 1.49, 95% CI = 1.22–1.83) and stage I (OR = 1.21, 95% CI = 1.02–1.43], but not stage II through IV (OR = 0.83, 95% CI = 0.63–1.09), and was also associated with increased risk of basal cell carcinoma (OR = 1.19, 95% CI = 1.14–1.25). PDE5 inhibitor use was associated with higher educational level and annual income, both of which were significantly associated with increased melanoma risk.
The investigators concluded: “In a Swedish cohort of men, the use of PDE5 inhibitors was associated with a modest but statistically significant increased risk of malignant melanoma. However, the pattern of association (eg, the lack of association with multiple filled prescriptions) raises questions about whether this association is causal.”
Stacy Loeb, MD, of New York University, is the corresponding author for the JAMA article.
The study supported by the Swedish Research Council (825-2012-5047) and the Swedish Cancer Foundation, Västerbotten County Council, Lion’s Cancer Research Foundation at Umeå University, Louis Feil Charitable Lead Trust, and Laura and Isaac Perlmutter NYU Cancer Institute. For full disclosures of the study authors, visit jama.jamanetwork.com.
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