Use of phosphodiesterase type 5 inhibitors and risk of melanoma: a meta-analysis of observational studies

Background Phosphodiesterase type 5 inhibitor (PE5i) administration may stimulate the proliferation and survival of melanocytes. However, discrepancies remain regarding the association between PDE5i use and melanoma risk in observational studies in humans. Aim To evaluate the association between PDE5i use and melanoma in a meta-analysis. Materials and methods Studies were identified by searching the PubMed and Embase databases. A random-effects model was applied to synthesize the data. A stratified study was performed to evaluate the influence of study characteristics on outcomes. Results Four prospective cohort studies and three case-control studies with 1,534,615 male participants and 16,053 melanoma cases were incorporated. Patients who received a PDE5i had a significantly increased risk for melanoma (adjusted risk ratio [RR] =1.12, 95% CI =1.03-1.33, P=0.008) with moderate heterogeneity (I2=54%). Cohort studies (adjusted RR =1.22, 95% CI =1.02-1.46, P=0.03) largely contributed to this result rather than case-control studies. Subsequent stratified analyses revealed that sildenafil was associated with an increased risk of melanoma (adjusted RR =1.26, 95% CI =1.07-1.50, P=0.007), but tadalafil and vardenafil were not. Also, PDE5i use was associated with a significantly increased risk of in situ melanoma (adjusted RR =1.31, 95% CI =1.01-1.69, P=0.04), but not of localized or nonlocalized melanoma. Conclusion PDE5i use may be associated with a significantly increased risk for melanoma in men. However, further research is needed to determine whether the association is causative.