Phosphodiesterase Type 5 Inhibitors and Risk of Skin Cancers in Men: A Meta-Analysis and Trial Sequential Analysis Involving 7,479,852 Subjects

PurposeWe conducted a systematic review and meta-analysis to quantify the association between phosphodiesterase type 5 inhibitors (PDE5Is) use and skin cancers and we also examined whether down-expression of the PDE5A gene was related to worse prognosis for malignant melanoma (MM) patients.Materials and MethodsThe PubMed, Cochrane Library, Web of Science, EMBASE, and ClinicalTrails.gov databases were searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between PDE5Is use and risk of skin cancers. Cumulative meta-analysis and trial sequential analysis (TSA) were also conducted. Survival outcomes were analyzed online.ResultsAfter pooling all 8 eligible studies comprising 7,479,852 subjects, we found that PDE5Is use was significantly associated with slightly increased risk of developing MM (OR: 1.13, 95% CI: 1.05 to 1.21, I2=67.1%), basal cell carcinoma (OR: 1.16, 95% CI: 1.13 to 1.19, I2=49.6%), and squamous cell carcinoma (OR: 1.07, 95% CI: 1.01 to 1.13, I2=0.0%). Totally, PDE5Is increased the risk of developing skin cancers (OR: 1.13, 95% CI: 1.09 to 1.17, I2=70.8%). TSA results showed that the sample size was enough to reach a positive conclusion.ConclusionsThe use of PDE5Is may be slightly associated with increased risk of developing skin cancers. There should be a balance between drug benefits and potential safety issues. However, the pooled results should be considered tentative until confounding factors such as sun exposure and lifestyle are well-controlled in further studies.