title: The Association between Phosphodiesterase Type 5 Inhibitors and Prostate Cancer: Results from the REDUCE Study.
abstract: OBJECTIVE
  Despite routine use of phosphodiesterase type 5 inhibitor to treat erectile dysfunction the role in prostate cancer chemoprevention remains unclear. Only a few studies have explored the link between phosphodiesterase type 5 inhibitor use and prostate cancer. We tested the association between phosphodiesterase type 5 inhibitor and prostate cancer risk in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial.
  
  
  METHODS
  REDUCE was a 4-year multicenter study testing the effect of daily dutasteride on prostate cancer risk in men with prostate specific antigen 2.5 to 10.0 ng/ml and negative biopsy who underwent study mandated biopsies at 2 and 4 years. The association of phosphodiesterase type 5 inhibitor with overall prostate cancer risk and disease grade (Gleason 2-6 and 7-10) was examined using adjusted logistic and multinomial regression analysis. Secondary analysis was performed to explore the association between phosphodiesterase type 5 inhibitor and prostate cancer risk in North American men, given the significantly higher use of phosphodiesterase type 5 inhibitor in these subjects.
  
  
  RESULTS
  Phosphodiesterase type 5 inhibitor was not associated with prostate cancer diagnosis (OR 0.90, 95% CI 0.68-1.20, p = 0.476), low grade disease (OR 0.93, 95% CI 0.67-1.27, p = 0.632) or high grade disease (OR 0.85, 95% CI 0.51-1.39, p = 0.508). An inverse trend was seen between phosphodiesterase type 5 inhibitor and prostate cancer diagnosis in North American men but this was not statistically significant (OR 0.67, 95% CI 0.42-1.07, p = 0.091).
  
  
  CONCLUSIONS
  Phosphodiesterase type 5 inhibitor use was not associated with decreased prostate cancer diagnoses on post-hoc analysis of REDUCE. In North American men, who had much higher baseline use of phosphodiesterase type 5 inhibitor, this treatment was associated with an inverse trend of prostate cancer diagnosis that approached but did not reach statistical significance.
authors.affiliation: Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Juzar
authors.initials: J
authors.lastname: Jamnagerwalla
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina; Surgery Section, Durham Veterans Affairs Medical Center, Durham, North Carolina.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Howard
authors.affiliation: Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Vidal
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Moreira
authors.affiliation: Research and Development, GlaxoSmithKline, Inc., King of Prussia, Pennsylvania.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Castro-Santamaria
authors.affiliation: Washington University School of Medicine in St. Louis, St. Louis, Missouri.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Andriole
authors.affiliation: Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California; Surgery Section, Durham Veterans Affairs Medical Center, Durham, North Carolina. Electronic address: Stephen.Freedland@cshs.org.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use; D000368:Aged; D001706:Biopsy; D004311:Double-Blind Method; D000068538:Dutasteride / Q000627:therapeutic use*; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D012307:Risk Factors
chemical_list: D058891:5-alpha Reductase Inhibitors; D017430:Prostate-Specific Antigen; D000068538:Dutasteride
keywords: chemoprevention; erectile dysfunction; phosphodiesterase 5 inhibitors; prostatic neoplasms; risk