Alpha-blockers for Enlarged Prostate May Lower Parkinson’s Risk

Some medications currently used to treat enlarged prostate, such as alpha-1 adrenergic receptor antagonists — called alpha-blockers — might lower the risk of Parkinson’s disease, according to a new study.

While more research is needed to fully determine a causal effect of alpha-blockers in treating the neurodegenerative disease, scientists said these medications could “potentially prevent — and not just manage — Parkinson’s.”

The study, “Association of Glycolysis-Enhancing α-1 Blockers With Risk of Developing Parkinson Disease,” was published in JAMA Neurology.

One of the hallmark biological features of Parkinson’s disease is impaired metabolism. Specifically, that means that cells are unable to generate the energy they need to survive and carry out their functions.

Alpha-blockers are a class of medication used to treat benign prostate hyperplasia, or non-cancerous enlarged prostate. Recently, scientists found that some alpha-blockers — namely terazosin (TZ), doxazosin (DZ), and alfuzosin (AZ) — have metabolism-enhancing effects, distinct from their effects on the prostate. Previous research showed that these medications slow Parkinson’s progression in animal models.

In the new study, researchers analyzed patient information from two national databases, one each from the U.S. and Denmark.

In the Danish database, 52,365 men were identified as having been treated with terazosin, doxazosin, or alfuzosin. In the U.S. database, 94,883 men had been treated with the same three medications, the researchers found. In both groups, the mean age was in the mid-60s, with the Danish men slightly older.

For comparison, in each database, the researchers identified the same number of people, matched based on age, who started treatment with another alpha-blocker called tamsulosin. While tamsulosin has the same prostate-specific effects as other alpha-blockers, it does not have the metabolism-enhancing effects of terazosin, doxazosin, or alfuzosin.

Because these medicines are used for the same conditions, the two groups were similar in most respects, with the metabolism-specific medication effects being the key difference.

“We then tracked the health data on these men to determine how many in each group developed Parkinson’s disease,” Jacob Simmering, PhD, a professor of internal medicine at the University of Iowa and co-author of the study, said in a press release.

Among the Danish group, 798 terazosin/doxazosin/alfuzosin users developed Parkinson’s, compared with 939 men given tamsulosin. In the U.S. dataset, a total of 862 men who used terazosin/doxazosin/alfuzosin developed Parkinson’s versus 1,368 tamsulosin users.

Statistical analyses demonstrated that, compared with individuals on tamsulosin, men on terazosin, doxazosin, or alfuzosin were significantly less likely to develop Parkinson’s. Indeed, the men in the Danish dataset had a 12% lower risk and those in the U.S. group saw their risk decrease by 37%.

“While the designs and outcome definitions used in the analyses were roughly parallel, differences between the 2 countries’ health care systems and coding practices make direct comparison between the [U.S. group] and the Danish [patients] difficult,” the researchers wrote.

However, the results overall across the two groups suggest that the alpa-blockers lessened the risk of Parkinson’s.

Many of the results were similar. For example, generally, longer use of terazosin, doxazosin, or alfuzosin was associated with a greater reduction in Parkinson’s risk. The researchers noted that the risk-lowering effects of these medications seemed more pronounced in individuals ages 70 or older, but age-based differences were not statistically significant in either dataset.

“Despite the relative differences in population and health care system structure, we found a similar protective effect in both countries,” Simmering said.

Moreover, “the replication of the finding in an international [patient group] is powerful evidence suggesting a causal [cause-and-effect] effect,” he said.

The researchers nonetheless stressed that, because of this study’s observational design, it’s impossible to conclusively say whether terazosin, doxazosin, or alfuzosin lowers prostate cancer risk — further study will be needed to determine this definitively. Also of note, the ways in which Parkinson’s develops and progresses varies from person to person, the researchers said, so additional study may be needed to identify the individuals who would most benefit from these or other metabolism-targeting treatments.

“Future work, especially in the form of randomized trials, are needed to fully resolve questions related to the causal effect of TZ/DZ/AZ,” the researchers wrote.

“If these results are confirmed through further investigation, especially a randomized clinical trial, terazosin may provide neuroprotection and potentially prevent — and not just manage —Parkinson’s disease,” Simmering said.