Use of drugs commonly used to treat enlarged prostate was associated with a reduced risk of developing Parkinson disease in men.
Use of terazosin, doxazosin, and alfuzosin—drugs commonly used to treat enlarged prostate—was associated with a reduced risk of developing Parkinson disease (PD) in men, according to study findings published yesterday in JAMA Neurology.
As researchers highlight, impaired energy metabolism is a potential and largely unexplored pathogenic factor in PD, in which patients’ glycolysis and mitochondria function are decreased.
A prior study conducted by the same researchers on terazosin, an α-1 adrenergic receptor antagonist that is commonly used to manage benign prostatic hyperplasia, uncovered that the drug and closely related α-1 adrenergic receptor antagonists, doxazosin and alfuzosin, bind and enhance cellular energy levels.
Moreover, these drugs were shown to prevent or slow the progression of PD in animal models and in men with PD, from the Truven Health Analytics MarketScan database in the United States, who had been taking 1 of the medications.
Seeking to further examine this potential link in men, the study authors assessed 2 patient data sets, the Truven database from January 2001 to December 2017 and national health registries in Denmark from January 1996 to December 2017. Researchers compared men without PD who newly initiated terazosin/doxazosin/alfuzosin therapy or tamsulosin therapy, a drug with a similar indication used to treat enlarged prostate but that does not enhance cellular energy levels.
Propensity score–matched male pairs of terazosin/doxazosin/alfuzosin users and tamsulosin users in the Danish registries (N = 52,365; mean [SD] age, 67.9 [10.4] years) and the Truven database (N = 94,883; mean [SD] age, 63.8 [11.1] years) were followed 1 year after the onset of treatment. HRs were utilized to distinguish the differences between the 2 treatment groups in developing diagnosed PD or using PD-specific medications.
In assessing both data set cohorts, patients who underwent terazosin/doxazosin/alfuzosin therapy exhibited a lower risk of developing PD, as patients in the Danish cohort had an HR of 0.88 (95% CI, 0.81-0.98) and patients in the Truven cohort had an HR of 0.63 (95% CI, 0.58-0.69).
"Despite the relative differences in population and health care system structure, we found a similar protective effect in both countries," noted study author Jacob Simmering, PhD, assistant professor of internal medicine at the University of Iowa, in a statement.
Additionally, a dose-response association was found with short-duration, medium-duration, and long-duration use of terazosin/doxazosin/alfuzosin: Long-duration users were associated with the lowest risk of developing PD of those observed in both the Danish cohort (short: HR, 0.95; 95% CI, 0.84-1.07; medium: HR, 0.88; 95% CI, 0.77-1.01; long: HR, 0.79; 95% CI, 0.66-0.95) and the Truven cohort (short: HR, 0.70; 95% CI, 0.64-0.76; medium: HR, 0.58; 95% CI, 0.52-0.64; long: HR, 0.46; 95% CI, 0.36-0.57).
“The replication of the finding in an international cohort is powerful evidence suggesting a causal effect,” concluded Simmering. “If these results are confirmed through further investigation, especially a randomized clinical trial, terazosin may provide neuroprotection and potentially prevent—and not just manage—PD.”
Simmering JE, Welsh MJ, Liu L, Narayanan NS, Pottegård A. Association of glycolysis-enhancing α-1 blockers with risk of developing Parkinson disease. JAMA Neurol. Published online February 1, 2020. doi:10.1001/jamaneurol.2020.5157