Taking a particular type of medication to treat an enlarged prostate is associated with a reduced risk of developing Parkinson's disease, according to a large observational study across the US, Denmark and China.
The findings provide compelling evidence that terazosin, and similar medications, might have the potential to prevent or delay the development of Parkinson's disease.
The study used data on almost 300,000 older men from two large, independent patient datasets – the Truven Health Analytics MarketScan database in the US and national health registries in Denmark – to investigate whether taking terazosin is associated with the development of Parkinson's disease.
The findings build on previous preclinical research by the team, which showed that terazosin enhances cellular energy levels and can prevent or slow the progression of Parkinson's disease in animal models. In this earlier study, the team also used the Truven database to show that men with Parkinson's disease who were also taking terazosin and related drugs had reduced signs, symptoms, and complications of Parkinson's disease.
Importantly, the researchers had a good control group for this earlier database study. Tamsulosin is another drug commonly used to treat enlarged prostate, but unlike terazosin, tamsulosin has no effect on cellular energy production, which the team's lab studies suggest is important in terazosin's protective effect.
The study extends these findings to investigate whether terazosin, and related drugs that can also enhance cellular energy production, are associated with a reduced risk of developing Parkinson's disease.
Using the US and Danish databases, the team identified 150,000 men newly started on terazosin or similar medications and matched them, based on age and clinical history to 150,000 men newly started on tamsulosin.
"We then tracked the health data on these men to determine how many in each group developed Parkinson's disease," explains Dr Jacob Simmering, UI assistant professor of internal medicine and corresponding author of the study. "Men taking terazosin were 12% to 37% less likely to develop Parkinson's disease during follow-up than men taking tamsulosin."
Additionally, the study found that longer duration of use of the energy-enhancing prostate drugs was associated with increased protective effects.
"Despite the relative differences in population and health care system structure, we found a similar protective effect in both countries," Simmering adds. "The replication of the finding in an international cohort is powerful evidence suggesting a causal effect. If these results are confirmed through further investigation, especially a randomised clinical trial, terazosin may provide neuroprotection and potentially prevent – and not just manage – Parkinson's disease."
Association of Glycolysis-Enhancing α-1 Blockers With Risk of Developing Parkinson Disease.
Jacob E Simmering; Michael J Welsh; Lei Liu; Nandakumar S Narayanan; Anton Pottegård
Published in JAMA Neurology on 1 February 2021
Parkinson disease (PD) is a common neurodegenerative disease. A treatment that prevents or delays development of PD is a critical unmet need. Terazosin and closely related drugs were recently discovered to enhance glycolysis and reduce PD progression in animal models and human clinical databases.
To determine whether use of terazosin, doxazosin, and alfuzosin is associated with a decreased risk of developing PD.
Design, Setting, and Participants
This cohort study used active comparator control and propensity score–matched data from Danish nationwide health registries, including the Danish National Prescription Registry, the Danish National Patient Registry, and the Danish Civil Registration System, from January 1996 to December 2017 and data from the Truven Health Analytics MarketScan database from January 2001 to December 2017. Men without PD who newly initiated terazosin/doxazosin/alfuzosin therapy or tamsulosin therapy, which is used for a similar indication (benign prostatic hyperplasia or unspecified urinary problems) but does not enhance glycolysis, and had at least 1 year of follow-up after medication start were included. In Denmark, the database included all residents, while the Truven database is a compilation of insurance claims across the US. Data were analyzed from February 2019 to July 2020.
Patients who used terazosin/doxazosin/alfuzosin vs tamsulosin. Additional dose-response analyses were carried out.
Main Outcomes and Measures
Differences in the hazard of developing PD identified by diagnoses or use of PD-specific medications between patients who ever used terazosin/doxazosin/alfuzosin or tamsulosin.
A cohort of 52 365 propensity score–matched pairs of terazosin/doxazosin/alfuzosin and tamsulosin users were identified in the Danish registries, of which all were male and the mean (SD) age was 67.9 (10.4) years, and 94 883 propensity score–matched pairs were identified in the Truven database, of which all were male and the mean (SD) age was 63.8 (11.1) years. Patients in the Danish cohort who used terazosin/doxazosin/alfuzosin had a hazard ratio (HR) for developing PD 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). There was a dose-response association with short-duration, medium-duration, and long-duration use of terazosin/doxazosin/alfuzosin users having a decreasing HR 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 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).
Conclusions and Relevance
These data suggest that users of terazosin/doxazosin/alfuzosin are at lower hazard of developing PD compared with users of tamsulosin. Future work is needed to further assess this association.
University of Iowa Healthcare material
JAMA Neurology study (Open access)
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