World J Mens Health.  2021 Oct;39(4):683-696. 10.5534/wjmh.200082.

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

Affiliations
  • 1Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
  • 27th Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  • 3Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China

Abstract

Purpose
We 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 Methods
The 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.
Results
After 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.
Conclusions
The 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.

Keyword

Erectile dysfunction; Melanoma; Meta-analysis; Phosphodiesterase type 5 inhibitors; Skin neoplasms
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