Treatment Regimen for Benign Prostatic Hyperplasia Reduces Risk of Dementia With Lewy Bodies in Men
Research published in Neurology last month demonstrated that terazosin, doxazosin, and alfuzosin (Tz/Dz/Az), medications commonly used for the treatment of benign prostatic hyperplasia (BPH), are associated with a lower risk of dementia with Lewy bodies (DLB).
Tz/Dz/Az are ⍺-1 blockers that have been shown to reduce aggregation of alpha-synuclein in animal models of Parkinson’s disease and improve symptoms in patients with Parkinson’s. Impaired cellular metabolic activity is implicated in Parkinson’s disease, and Tz/Dz/Az increases the availability of adenosine triphosphate (ATP), which is a primary cellular energy source. Tz/Dz/Az acts by activating phosphoglycerate kinase-1 (PGK1), an ATP-producing enzyme. The study authors hypothesized that activating PGK1 increases ATP and mitigates neurodegeneration by improving the ability of cells to adapt to aging and synuclein aggregation.
Researchers utilized databases which include public insurance claims data for 200 million people (the Merative Marketscan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits). Two active comparator medications were selected for the study—tamsulosin, an α-1 blocker that does not bind to PGK1 or increase ATP, and 5α-reductase inhibitors (5ARI) finasteride and dutasteride, which neither target α-1 nor increase ATP.
Insurance claims were used to identify new male users of each of the treatment regimens of interest. The primary outcome was time from medication start to a diagnosis of DLB in any setting. After applying exclusion criteria and propensity score matching used to control for potential differences in the study cohorts, the study sample resulted in 121,358 pairs of men for the Tz/Dz/Az vs tamsulosin analysis, 65,436 pairs of men for the Tz/Dz/Az vs 5ARI analysis, and 79,798 pairs of men for the tamsulosin vs 5ARI analysis.
After a mean follow-up of approximately three years, men taking Tz/Dz/Az had lower hazard ratios (probability) of developing DLB than men taking tamsulosin (HR 0.60, 95% CI 0.50–0.71) or 5ARI (HR 0.73, 95% CI 0.57–0.93), while men taking tamsulosin had similar hazard ratio to men taking 5ARI (HR 1.17, 95% CI 0.96–1.42). The results remained largely consistent after controlling for various potentially confounding variables.
“Taken together, these data provide evidence for a potential neuroprotective role of Tz/Dz/Az in the development of DLB,” conclude the authors, who note that randomized trials will be needed to determine causality.
