Use of Glycolysis‐Enhancing Drugs and Risk of Parkinson's Disease

Background Terazosin (TZ) and closely related α1‐adrenergic receptor antagonists (doxazosin [DZ] and alfuzosin [AZ]) enhance glycolysis and reduce neurodegeneration in animal models. Observational evidence in humans from several databases supports this finding; however, a recent study has suggested that tamsulosin, the comparator medication, increases the risk of Parkinson's disease. Aims We consider a different comparison group of men taking 5α‐reductase inhibitors (5ARIs) as a new, independent comparison allowing us to both obtain new estimates of the association between TZ/DZ/AZ and Parkinson's disease outcomes and validate tamsulosin as an active comparator. Methods Using the Truven Health Analytics Marketscan database, we identified men without Parkinson's disease, newly started on TZ/DZ/AZ, tamsulosin, or 5ARIs. We followed these matched cohorts to compare the hazard of developing Parkinson's disease. We conducted sensitivity analyses using variable duration of lead‐in to mitigate biases introduced by prodromal disease. Results We found that men taking TZ/DZ/AZ had a lower hazard of Parkinson's disease than men taking tamsulosin (hazard ratio (HR) = 0.71, 95% CI [confidence interval]: 0.65–0.77, n = 239,888) and lower than men taking 5ARIs (HR = 0.84, 95% CI: 0.75–0.94, n = 129,116). We found the TZ/DZ/AZ versus tamsulosin HR to be essentially unchanged with up to 5 years of lead‐in time; however, the TZ/DZ/AZ versus 5ARI effect became attenuated with longer lead‐in durations. Conclusions These data suggest that men using TZ/DZ/AZ have a somewhat lower risk of developing Parkinson's disease than those using tamsulosin and a slightly lower risk than those using 5ARIs. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society