| Summary: | Recent studies reported conflicting results on the association of androgen deprivation therapy (ADT) with dementia and Parkinson's disease in patients with prostate cancer (Pca). Therefore, this study aimed to investigate whether use of gonadotropin-releasing hormone agonist (GnRHa) increases the risk of both diseases. A nationwide population cohort study was conducted involving newly diagnosed patients with Pca %who started ADT with GnRHa (GnRHa users, n = 3,201) and control (nonusers, n = 4,123) between January 1, 2012, and December 31, 2016, using data from the National Health Insurance Service. To validate the result, a hospital cohort of patients with Pca consisting of GnRHa users (n = 205) and nonusers (n = 479) in a tertiary referral center from January 1, 2006 to December 31, 2016, were also analyzed. Traditional and propensity score-matched Cox proportional hazards models were used to estimate the effects of ADT on the risk of dementia and Parkinson's disease. In univariable analysis, risk of dementia was associated with GnRHa use in both nationwide and hospital validation cohort (hazard ratio [HR], 1.696; 95% CI, 1.425-2.019, and HR, 1.352; 95% CI, 1.089-1.987, respectively). In a nationwide cohort, ADT was not associated with dementia in both traditional and propensity score-matched multivariable analysis, whereas in a hospital validation cohort, ADT was associated with dementia only in unmatched analysis (HR, 1.203; 95% CI, 1.021-1.859) but not in propensity score-matched analysis. ADT was not associated with Parkinson's disease in either nationwide and validation cohorts. This population-based study suggests that the association between GnRHa use as ADT and increased risk of dementia or Parkinson's disease is not clear, which was also verified in a hospital validation cohort.
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