Skov, Renata P.H.

Phosphodiesterase type 5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction, with modest adverse effects. Since 2011, concerns have arisen about increased melanoma risk in PDE5 inhibitor users. PDE5 inhibitors affect the rat sarcoma virus oncogene–rapidly accelerated fibrosarcoma–mitogen‐activated protein kinase–extracellular signal‐regulated kinase signaling cascade, which is involved in melanoma formation. This systematic review and meta-analysis investigates melanoma risk in PDE5 inhibitor users. PubMed, Cochrane, and Embase were searched to examine the relationship between PDE5 inhibitors and melanoma. A random-effects model estimated pooled odds ratios (ORs) and hazard ratios (HRs), with the I² statistic assessing heterogeneity. RStudio v4.4.2 was used for the meta-analysis, and a P value less than 0.05 was deemed significant. Eight studies including 7 620 765 patients were analyzed, with 2 123 165 (27.86%) comprising the PDE5 inhibitor-exposed group. The meta-analysis found a relationship between PDE5 inhibitor use and increased melanoma risk [OR: 1.60, 95% confidence interval (CI): 1.13–2.27, P = 0.009, I² = 98%] and [HR: 1.10, 95% CI: 1.03–1.17, P = 0.005, I² = 43%]. When each PDE5 inhibitor was examined separately, increased melanoma incidence was observed, though not statistically significant. The OR for sildenafil was 1.85 (95% CI: 0.97–3.51, P = 0.059, I² = 99%), tadalafil 1.54 (95% CI: 0.79–3.00, P = 0.203, I² = 96%), and vardenafil 1.16 (95% CI: 0.82–1.64, P = 0.391, I² = 89%). This study suggests PDE5 inhibitor users have a higher chance of developing potentially fatal melanoma. Patients with a history of skin cancer, a family history of melanoma, or other risk factors should avoid these medications.