Risk of dementia and Parkinson's disease in patients treated with androgen deprivation therapy using gonadotropin-releasing hormone agonist for prostate cancer: A nationwide population-based cohort study

PLoS One. 2020 Dec 30;15(12):e0244660. doi: 10.1371/journal.pone.0244660. eCollection 2020.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cohort Studies
  • Dementia / epidemiology*
  • Dementia / etiology
  • Gonadotropin-Releasing Hormone / adverse effects
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / epidemiology*
  • Parkinson Disease / etiology
  • Propensity Score
  • Prostatic Neoplasms / drug therapy*
  • Survival Analysis
  • Tertiary Care Centers
  • Treatment Outcome

Substances

  • Gonadotropin-Releasing Hormone
  • LHRH, Ala(6)-Gly(10)-ethylamide-

Grants and funding

This research was supported by Hallym University Research Fund 2018(H20180251) received by MS. URL: https://sanhak.hallym.ac.kr/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.