The RAS/RAF/MEK/ERK signaling pathway plays a crucial role in melanoma cell proliferation and survival. Sildenafil (Viagra) is a phosphodiesterase (PDE) 5A inhibitor commonly used for erectile dysfunction. Recent studies have shown that BRAF activation down-regulates PDE5A levels, and low PDE5A expression by BRAF activation or sildenafil use increases the invasiveness of melanoma cells, which raises the possible adverse effect of sildenafil use on melanoma risk.
To evaluate the association between sildenafil use and risk of incident melanoma among men in the United States.
Design, Setting and Participants Design
In 2000, participants in the Health Professionals’ Follow-up Study (HPFS), an ongoing prospective study. were inquired regarding sildenafil use for erectile dysfunction. We excluded baseline cancers, type 2 diabetes, coronary heart disease, stroke, and hypertension. A total of 14,912 men were included.
Main Outcome Measure
Incidence of skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) was obtained in the self-reported questionnaires biennially. The diagnosis of melanoma and SCC was pathologically confirmed.
We identified 79 melanoma, 305 SCC, and 1,720 BCC cases during the follow-up (2000–2010). Sildenafil use was significantly associated with an increased risk of subsequent melanoma with a multivariate-adjusted hazard ratio (HR) of 2.24 (95% confidence interval (CI): 1.05–4.78). In contrast, we did not observe an increase in risk of SCC (HR = 0.80, 95% CI: 0.46–1.37), or BCC (HR = 1.05, 95% CI: 0.84–1.30) associated with sildenafil use. Moreover, erectile function itself was not associated with an altered risk of melanoma.
Sildenafil use may be associated with an increased risk of developing melanoma.