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Authors Han X, Han Y, Zheng Y, Sun Q, Ma T, Dai L, Zhang J, Xu L
Received 26 May 2017
Accepted for publication 20 October 2017
Published 5 February 2018 Volume 2018:11 Pages 711—720
DOI https://doi.org/10.2147/OTT.S142637
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Samir Farghaly
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 (I 2=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.
Keywords: phosphodiesterase type 5 inhibitors, melanoma, meta-analysis,
sildenafil