title: Androgen deprivation therapy and the risk of parkinsonism in men with prostate cancer.
abstract: OBJECTIVE
  Case reports and anecdotal experiences suggest that some men develop parkinsonism after initiating androgen deprivation therapy (ADT) for the treatment of prostate cancer, possibly due to neurophysiological effects of changes in testosterone and/or estrogen. We hypothesized that ADT would increase the risk of parkinsonism.
  
  
  METHODS
  Using linked administrative databases in Ontario, Canada, men age 40 or older with prostate cancer on continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 38,931) were matched 1:1 with men with prostate cancer who had never received ADT. Treated and untreated groups were range-matched on age at index date and year of diagnosis, and propensity-matched on comorbidities, medications, cardiovascular risk factors, and socio-economic variables. A competing risk analysis was conducted where the primary outcome was time to a new diagnosis of parkinsonism.
  
  
  RESULTS
  The cohort was followed for a mean of 5.76 years. Based on the results from the multivariable cause-specific hazard regression model, the adjusted relative rate of experiencing parkinsonism among ADT users compared to non-users was 0.74 (95% confidence interval (CI) 0.67-0.83, p < 0.0001). The adjusted relative rate of experiencing the competing event of death among ADT users compared to non-users was 1.33 (95% CI 1.30-1.36, p < 0.0001). The 5-year incidence of parkinsonism was 1.03% in ADT users versus 1.56% in non-users.
  
  
  CONCLUSIONS
  Contrary to our hypothesis, continuous ADT use for at least 6 months in men with prostate cancer was not associated with an increased risk of parkinsonism after accounting for the substantial competing risk of death.
authors.affiliation: Departments of Medicine, University of Toronto, Toronto, ON, Canada. james.young@williamoslerhs.ca.|Brampton Civic Hospital, N4. 760, 2100 Bovaird Drive East, Brampton, ON, L6R 3J7, Canada. james.young@williamoslerhs.ca.
authors.forename: James W S
authors.initials: JWS
authors.lastname: Young
authors.affiliation: The Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
authors.forename: Rinku
authors.initials: R
authors.lastname: Sutradhar
authors.affiliation: The Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
authors.forename: Jagadish
authors.initials: J
authors.lastname: Rangrej
authors.affiliation: Department of Neurology, University of Toronto, Toronto, ON, Canada.
authors.forename: Connie
authors.initials: C
authors.lastname: Marras
authors.affiliation: Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: Fleshner
authors.affiliation: Departments of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Shabbir M H
authors.initials: SMH
authors.lastname: Alibhai
mesh_terms: D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D016022:Case-Control Studies; D015331:Cohort Studies; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009864:Ontario / Q000453:epidemiology; D009919:Orchiectomy; D020734:Parkinsonian Disorders / Q000453:epidemiology*; D057216:Propensity Score; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000628:therapy*; D012307:Risk Factors
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone
keywords: Androgen deprivation therapy; Parkinsonism; Parkinson’s disease; Prostate cancer