title: 5α-Reductase inhibitors and risk of high-grade or lethal prostate cancer.
abstract: OBJECTIVE
  5α-Reductase inhibitors (5ARIs) are widely used for benign prostatic hyperplasia despite controversy regarding potential risk of high-grade prostate cancer with use. Furthermore, the effect of 5ARIs on progression and prostate cancer death remains unclear.
  
  
  OBJECTIVE
  To determine the association between 5ARI use and development of high-grade or lethal prostate cancer.
  
  
  METHODS
  Prospective observational study of 38,058 men followed up for prostate cancer diagnosis and outcomes between 1996 and 2010 in the Health Professionals Follow-up Study.
  
  
  METHODS
  Use of 5ARIs between 1996 and 2010.
  
  
  METHODS
  Cox proportional hazards models were used to estimate risk of prostate cancer diagnosis or development of lethal disease with 5ARI use, adjusting for possible confounders including prostate specific antigen testing.
  
  
  RESULTS
  During 448,803 person-years of follow-up, we ascertained 3681 incident prostate cancer cases. Of these, 289 were lethal (metastatic or fatal), 456 were high grade (Gleason sum [GS] 8-10), 1238 were GS 7, and 1600 were low grade (GS 2-6). A total of 2878 (7.6%) men reported use of 5ARIs between 1996 and 2010. After adjusting for confounders, men who reported ever using 5ARIs over the study period had a reduced risk of overall prostate cancer (hazard ratio [HR], 0.77; 95% CI, 0.65-0.91). 5ARI users had a reduced risk of GS 7 (HR, 0.67; 95% CI, 0.49-0.91) and low-grade (GS 2-6) prostate cancer (HR, 0.74; 95% CI, 0.57-0.95). 5ARI use was not associated with risk of high-grade (GS 8-10) prostate cancer (HR, 0.97; 95% CI, 0.64-1.46) or lethal disease (HR, 0.99; 95% CI, 0.58-1.69). Increased duration of use was associated with significantly lower risk of overall prostate cancer (HR for 1 year of additional use, 0.95; 95% CI, 0.92-0.99), localized (HR, 0.95; 95% CI, 0.90-1.00), and low-grade disease (HR, 0.92; 95% CI, 0.85-0.99). There was no association for lethal, high-grade, or grade 7 disease.
  
  
  CONCLUSIONS
  While 5ARI use was not associated with developing high-grade or lethal prostate cancer, it was associated with a reduction in low-grade, GS 7, and overall prostate cancer. Because the number of patients with high-grade or lethal prostate cancer in our cohort was limited, we cannot rule out potential risk of harm with 5ARI use.
authors.affiliation: Department of Urology, Massachusetts General Hospital, Boston.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Preston
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts3Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Wilson
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Markt
authors.affiliation: Department of Urology, Massachusetts General Hospital, Boston.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Ge
authors.affiliation: Division of Urology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Morash
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts3Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.affiliation: Departments of Pathology and Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's and Hospital, Boston, Massachusetts6Broad Institute of Harvard and MIT, Cambridge, Massachusetts7Division of Cancer Studies, King's College London, London, En.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts3Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts8Department of Nutrition, Harva.
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts3Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.affiliation: Department of Urology, Massachusetts General Hospital, Boston.
authors.forename: Aria F
authors.initials: AF
authors.lastname: Olumi
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors
chemical_list: D058891:5-alpha Reductase Inhibitors