Discovering new drugs is costly and fraught with uncertainty. Drug repurposing saves time and money by identifying new uses for drugs already approved or under investigation by the U.S. Food and Drug Administration. The FDA approved finasteride in 1992 under the brand name Proscar to treat benign prostatic hyperplasia in men, and again in 1997 under the brand name Propecia to treat male pattern baldness.
Researchers at the University of Illinois at Urbana-Champaign recently discovered another potential use for finasteride: preventing cardiovascular disease (CVD). In a study published in the Journal of Lipid Research, the team hypothesized that finasteride may lower cholesterol levels, thereby reducing the risk of heart disease.
The researchers studied the effects of finasteride in male mice and analyzed data from men who participated in the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2016.
Finasteride is a 5-alpha reductase inhibitor that prevents the conversion of testosterone to dihydrotestosterone (DHT), an active metabolite that plays an important role in the development of male genitalia, hair patterns, and prostate growth.
Donald Molina, a graduate student at the University of Illinois and lead author of the study, explained that low testosterone levels in men increase their risk of CVD.
“Because this drug affects testosterone levels, we wondered if there was a link between this drug and heart disease,” he said. “That was our starting point. We investigated how finasteride affects lipid profiles in humans.”
The research team first analyzed data archived in NHANES and found that finasteride use was associated with reductions in total cholesterol and low-density cholesterol.
“These results prompted us to move forward with animal studies,” Molina said.
The researchers used male mice that were genetically predisposed to atherosclerosis, a major underlying cause of heart disease. They fed the mice a high-fat, high-cholesterol diet and gave them four doses of finasteride. They monitored cholesterol and other lipid levels and studied gene expression and lipid metabolites.
Mice treated with finasteride had lower cholesterol levels, slowed the progression of atherosclerosis, reduced plasma triglycerides, and reduced liver inflammation.
Jaume Amenghal, an associate professor at the University of Illinois and lead author of the study, said his team believes the liver breaks down more lipids in the presence of finasteride.
“The liver is burning more fat,” Amenggal said. “Our findings are also relevant to fatty liver disease. If you have an unhealthy diet, you can accumulate a lot of fat in the liver, which can lead to liver inflammation and ultimately to cirrhosis and even cancer. So in our experiments, we saw that the fat content in the liver was reduced, and inflammation in the liver was reduced as well. Finasteride not only lowered plasma cholesterol levels, but it also improved liver function in mice.”
To confirm these findings, researchers will need detailed analyses of finasteride’s effects on statistically relevant populations and its metabolic side effects, such as on gut microbiota levels, as well as studies of its interactions with other drugs that target cholesterol synthesis or absorption.
“One of the reasons I got interested in this drug in the first place is because I’ve been taking it to treat hair loss since I was about 20 years old,” Amenggal said. “Although it has limitations, our study may provide a stepping stone to repurposing finasteride for cardiovascular disease prevention.”
