title: Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma.
abstract: OBJECTIVE
  The target for the oral erectile dysfunction drugs, phosphodiesterase type 5 (PDE5) inhibitors, is part of a pathway implicated in the development of malignant melanoma. An increased risk of melanoma in sildenafil users was recently reported.
  
  
  OBJECTIVE
  To examine the association between use of PDE5 inhibitors and melanoma risk, including data on specific PDE5 inhibitors, number of prescriptions, and melanoma stage.
  
  
  METHODS
  Nationwide, population-based, nested case-control study in the Swedish Prescribed Drug Register, the Swedish Melanoma Register, and other health care registers and demographic databases in Sweden, including 4065 melanoma cases diagnosed from 2006 through 2012 and 5 randomly selected controls per case with matching year of birth.
  
  
  METHODS
  Number of filled prescriptions for the PDE5 inhibitors sildenafil and vardenafil or tadalafil.
  
  
  METHODS
  Risk of melanoma; overall and by stage and risk of basal cell carcinoma in multivariable logistic regression analyses.
  
  
  RESULTS
  Of 4065 melanoma cases, 435 men (11%) had filled prescriptions for PDE5 inhibitors, as did 1713 men of 20,325 controls (8%). In multivariable analysis, there was an increased risk of melanoma in men taking PDE5 inhibitors (OR, 1.21 [95% CI, 1.08-1.36]). The most pronounced increase in risk was observed in men who had filled a single prescription (OR, 1.32 [95% CI, 1.10-1.59]; exposure rate, 4% for cases vs 3% for controls), but was not significant among men with multiple filled prescriptions (for 2-5 prescriptions: OR, 1.14 [95% CI, 0.95-1.37], 4% for cases and 3% for controls; for ≥6 prescriptions: OR, 1.17 [95% CI, 0.95-1.44], 3% for cases vs 2% for controls). PDE5 inhibitors were significantly associated with melanoma stage 0 (OR, 1.49 [95% CI, 1.22-1.83], 13% for cases vs 8% for controls) and stage I (OR, 1.21 [95% CI, 1.02-1.43], 12% for cases vs 10% for controls), but not stage II through IV (OR, 0.83 [95% CI, 0.63-1.09], 6% for cases vs 7% for controls). The risk estimates were similar for sildenafil and vardenafil or tadalafil. PDE5 inhibitor use was also associated with an increased risk of basal cell carcinoma (OR, 1.19 [95% CI, 1.14-1.25], 9% for cases vs 8% for controls). Men taking PDE5 inhibitors had a higher educational level and annual income, factors that were also significantly associated with melanoma risk.
  
  
  CONCLUSIONS
  In a Swedish cohort of men, the use of PDE5 inhibitors was associated with a modest but statistically significant increased risk of malignant melanoma. However, the pattern of association (eg, the lack of association with multiple filled prescriptions) raises questions about whether this association is causal.
authors.affiliation: Department of Urology, Population Health, and Laura and Isaac Perlmutter Cancer Center, New York University, New York.
authors.forename: Stacy
authors.initials: S
authors.lastname: Loeb
authors.affiliation: Uppsala University Hospital, Regional Cancer Center, Uppsala, Sweden.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Folkvaljon
authors.affiliation: Uppsala University Hospital, Regional Cancer Center, Uppsala, Sweden3Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Lambe
authors.affiliation: Department of Surgery and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London, United Kingdom.
authors.forename: Hans
authors.initials: H
authors.lastname: Garmo
authors.affiliation: Department of Surgery, Melanoma and Breast, Lund University Hospital, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.affiliation: Department of Surgery and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002280:Basal Cell Carcinoma / Q000139:chemically induced; D016022:Case-Control Studies; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000139:chemically induced*; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012042:Registries; D012307:Risk Factors; D012878:Skin Neoplasms / Q000139:chemically induced*; D012959:Socioeconomic Factors; D013548:Sweden
chemical_list: D058986:Phosphodiesterase 5 Inhibitors