4.8 Article

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

Journal

JOURNAL OF CLINICAL INVESTIGATION
Volume 131, Issue 11, Pages -

Publisher

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI145112

Keywords

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Funding

  1. Cerevel Therapeutics

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The study found that tamsulosin users had a significantly higher incidence of Parkinson's disease compared to terazosin/alfuzosin/doxazosin users and matched controls. There was no significant difference in Parkinson's disease risk between terazosin/alfuzosin/doxazosin users and matched controls. These results suggest that tamsulosin may exacerbate Parkinson's disease progression.
BACKGROUND. Recently the alpha(1) 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 alpha(1) 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. METHODS. To 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). RESULTS. Incidence 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). CONCLUSION. These 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.

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