5α-reductase

Pictured: Concept art showing an elderly woman overlaid with an illustration of a brain/iStock, boonstudio Drugs commonly used for the treatment of enlarged prostate may also help lower the risk of dementia with Lewy bodies, according to a new observational study from the University of Iowa Health Care. Drawing from Merative MarketScan, one of the largest proprietary U.S. healthcare claims databases, University of Iowa researchers identified more than 643,000 men who were starting treatment for benign prostatic hyperplasia with one of six common therapies. Three of these drugs fell under the class of α-1 adrenergic receptor antagonists, better known as α-blockers, which work by inhibiting the contraction of smooth muscles. The researchers focused on terazosin, which is sold by Abbott under the brand name Hytrin, doxazosin, which is marketed by Pfizer as Cardura, and alfuzosin, which is branded as Uroxatral by Sanofi. Alpha-blocker drugs are known to have a unique side effect: they activate a key enzyme involved in the production of ATP, which is the molecular form of cellular energy. In the brain, these drugs can help boost the production of energy and fight neurodegeneration, the University of Iowa scientists hypothesized. As active comparators, the researchers also followed men in Merative MarketScan who were being treated with tamsulosin or with the 5α-reductase inhibitors (5ARI) finasteride and dutasteride, all of which are not known to affect energy production in the brain. The men included in the study had no history of dementia with Lewy bodies (DLB). Participants were then followed until they exited the database or until they developed DLB. After an average follow-up of around three years, the study found that men who were initiated on the three alpha-blocker drugs were 40% less likely to develop DLB than comparators who were on tamsulosin. Compared with men whose enlarged prostates were being treated with 5ARI agents, the risk of DLBA was 27% lower in those taking alpha-blocker drugs. Both effects were statistically significant. By contrast, DLB had a statistically similar likelihood of developing in men being managed with tamsulosin and 5ARIs. These results were robust to several sensitivity analyses, according to researchers. The University of Iowa scientists published their findings Wednesday in Neurology, the medical journal of the American Academy of Neurology. “If terazosin and these similar medications can help slow this progression—if not outright preventing the disease—this would be important to preserving cognitive function and quality of life in people with DLB,” Jacob Simmering, assistant professor of internal medicine at the University of Iowa and lead study author, said in a statement. However, the researchers caution that the study is simply observational in design and only shows that there is a statistical correlation between the use of alpha-blocker drugs and the reduced risk of DLB. It does not establish causation nor does it show any directionality of association, they said. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

WEDNESDAY, June 19, 2024 -- Men taking α-1 adrenergic receptor antagonists terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) seem to have a lower risk for dementia with Lewy bodies (DLB), according to a study published online June 19 in Neurology . Alexander Hart, M.D., M.P.H., from the University of Michigan in Ann Arbor, and colleagues used a new-user active comparator design in the Merative Marketscan database to identify men with no history of DLB who were newly initiated on Tz/Dz/Az or two comparator medications (α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitor [5ARI]) to examine the potential neuroprotective effects of Tz/Dz/Az. The researchers found that the risk for developing DLB was lower for men who were newly started on Tz/Dz/Az than those taking tamsulosin or 5ARI (hazard ratios, 0.60 and 0.73, respectively), while the risk was similar for men taking tamsulosin versus 5ARI. The results were robust to sensitivity analyses. "More research is needed to follow people over time and determine whether there is a cause-and-effect relationship here, but it is promising to think that these drugs could have a protective effect on this disease that will likely affect a larger number of people as the population ages," coauthor Jacob E. Simmering, Ph.D., of the University of Iowa in Iowa City, said in a statement.

Certain drugs commonly used to treat enlarged prostate may also decrease the risk for dementia with Lewy bodies (DLB), according to a new study. The researchers think that a specific side effect of the drugs targets a biological flaw shared by DLB and other neurodegenerative diseases, raising the possibility that they may have broad potential for treating a wide range of neurodegenerative conditions. A new study suggests that certain drugs commonly used to treat enlarged prostate may also decrease the risk for dementia with Lewy bodies (DLB). This observational finding may seem surprising, but it mirrors previous work by the University of Iowa Health Care team that links the drugs to a protective effect in another neurodegenerative condition-Parkinson's disease. The UI researchers think that a specific side effect of the drugs targets a biological flaw shared by DLB and Parkinson's disease, as well as other neurodegenerative diseases, raising the possibility that they may have broad potential for treating a wide range of neurodegenerative conditions. "Diseases like dementia with Lewy bodies, or Parkinson's disease, or Alzheimer's disease, are debilitating and we don't really have any good treatments that can modify the disease progression. We can treat symptoms, but we can't actually slow the disease," explains lead study author Jacob Simmering, PhD, UI assistant professor of internal medicine. "One of the most exciting things about this study is that we find that same neuroprotective effect that we saw in Parkinson's disease. If there is a broadly protective mechanism, these medications could potentially be used to manage or prevent other neurodegenerative diseases." The new findings were published online on June 19, 2024, in Neurology®, the medical journal of the American Academy of Neurology. DLB is a neurodegenerative disease that causes substantial and rapid cognitive decline and dementia. While less common than Parkinson's disease, DLB affects about one in 1,000 people per year, and accounts for 3 to 7% of all dementia cases. Because aging is a key risk factor for DLB, it is likely to become more common as our population gets older. For the new study, the UI researchers used a large database of patient information to identify more than 643,000 men with no history of DLB who were newly starting one of six drugs used to treat benign prostatic hyperplasia (enlarged prostate). Three of the drugs, terazosin, doxazosin, and alfuzosin (Tz/Dz/Az), have an unexpected side effect; they can boost energy production in brain cells. Preclinical studies suggest that this ability may help slow or prevent neurodegenerative diseases like PD and DLB. The other drugs, tamsulosin and two 5-alpha-reductase inhibitors (5ARIs) called finasteride and dutasteride, do not enhance energy production in the brain and therefore provide a good comparison to test the effect of the Tz/Dz/Az drugs. The team then followed the data on these men from when they started taking the medication until they left the database or developed dementia with Lewy bodies, whichever happened first. On average, the men were followed for about three years. Because all the participants were selected to start a drug that treats the same condition, the researchers reasoned that the men were likely similar to each other at the outset of the treatment. The researchers also matched the men using propensity scores for characteristics like age, the year they started the medication, and other illnesses they had before staring the treatment, to further reduce the differences between the groups. "We found that men who took Tz/Az/Dz drugs were less likely to develop a diagnosis of dementia with Lewy bodies," Simmering says. "Overall, men taking terazosin-type medications had about a 40% lower risk of developing a DLB diagnosis compared to men taking tamsulosin, and about a 37% reduction in risk compared to men taking five alpha reductase inhibitors." Meanwhile, there wasn't a statistically significant difference in risk between men taking tamsulosin and 5-alpha reductase inhibitors. This was an observational study and therefore the results show only an association between taking the Tz/Dz/Az drugs and a reduced risk of developing DLB rather than a causal relationship. In addition, the study only included men because the drugs are prescribed for prostate problems, which means that the researchers don't know if the findings would apply to women. However, Simmering and his colleagues are excited by the potential of these drugs, which are already FDA approved, inexpensive, and have been used safely for decades. "If terazosin and these similar medications can help slow this progression -- if not outright preventing the disease -- this would be important to preserving cognitive function and quality of life in people with DLB," Simmering says. In addition to Simmering, the team included UI neuroscience researchers Nandakumar Narayanan, MD, PhD, Georgina Aldridge, MD, PhD, and Qiang Zhang, MD, and Alexander Hart, MD, who is now at University of Michigan.