Androgen deprivation therapy and the risk of parkinsonism in men with prostate cancer

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. 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. 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. 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.