Parkinson disease among patients treated for benign prostatic hyperplasia with α1 adrenergic receptor antagonists

J Clin Invest. 2021 Jun 1;131(11):e145112. doi: 10.1172/JCI145112.


BACKGROUNDRecently the α1 adrenergic receptor antagonist terazosin was shown to activate PGK1, a possible target for the mitochondrial deficits in Parkinson disease related to its function as the initial enzyme in ATP synthesis during glycolysis. An epidemiological study of terazosin users showed a lower incidence of Parkinson disease when compared with users of tamsulosin, an α1 adrenergic receptor antagonist of a different class that does not activate PGK1. However, prior research on tamsulosin has suggested that it may in fact potentiate neurodegeneration, raising the question of whether it is an appropriate control group.METHODSTo address this question, we undertook an epidemiological study on Parkinson disease occurrence rate in 113,450 individuals from the United States with 5 or more years of follow-up. Patients were classified as tamsulosin users (n = 45,380), terazosin/alfuzosin/doxazosin users (n = 22,690), or controls matched for age, sex, and Charlson comorbidity index score (n = 45,380).RESULTSIncidence of Parkinson disease in tamsulosin users was 1.53%, which was significantly higher than that in both terazosin/alfuzosin/doxazosin users (1.10%, P < 0.0001) and matched controls (1.01%, P < 0.0001). Terazosin/alfuzosin/doxazosin users did not differ in Parkinson disease risk from matched controls (P = 0.29).CONCLUSIONThese results suggest that zosins may not confer a protective effect against Parkinson disease, but rather that tamsulosin may in some way potentiate Parkinson disease progression.FUNDINGThis work was supported by Cerevel Therapeutics.

Keywords: Epidemiology; Genetics; Neuroscience; Parkinson disease.

Publication types

  • Comparative Study
  • Observational Study
  • Pragmatic Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic alpha-1 Receptor Antagonists* / administration & dosage
  • Adrenergic alpha-1 Receptor Antagonists* / adverse effects
  • Adult
  • Aged
  • Aged, 80 and over
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Parkinson Disease / epidemiology*
  • Prostatic Hyperplasia* / drug therapy
  • Prostatic Hyperplasia* / epidemiology


  • Adrenergic alpha-1 Receptor Antagonists

Grants and funding

All work was internal target validation research at Cerevel. Work done in collaboration with Optum Life Sciences was funded by Cerevel.