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Men with a genetic predisposition to high testosterone levels have a nearly eightfold increased risk of heart failure and twice the risk of thromboembolism (blood clots that can block veins or arteries leading to the brain or lungs), researchers found.
Although the study focuses on men with naturally high testosterone, it has implications for aging men who are taking testosterone supplements to boost their energy levels and improve their sex drive, experts said.
Testosterone sales increased 12-fold globally between 2000 and 2011, particularly in the United States, the researchers said in background notes.
“This study serves as a big, red stop sign, a warning that higher circulating levels of testosterone can lead to an increase in cardiovascular events, which are all associated with an increased risk of death,” said Dr. Guy Mintz. He is director of cardiovascular health and lipidology at Northwell Health’s Sandra Atlas Bass Heart Hospital in Manhasset, N.Y.
For the study, an international research team, led by C. Mary Schooling from the School of Public Health and Health Policy at City University of New York, analyzed genetic variants that predict testosterone levels, and then assessed whether those variants appeared to influence a person’s risk of blood clots, heart failure or heart attack.
The researchers found the testosterone genes by using data from 3,225 men, aged 50 to 75, who were participating in a worldwide prostate cancer prevention trial. The investigators checked the men’s levels of testosterone, and then looked to see if those with the highest levels had any shared genetic variants.
Next, the researchers compared these genes against medical data on more than 392,000 British men and women, to see if people carrying these genetic variations had an increased risk of blood clots, heart failure or heart attacks.
One testosterone-boosting gene in particular, the JMJD1C gene, was found to double the risk of dangerous blood clots in men and increase their risk of heart failure by 7.8 times.
A follow-up validation study involving nearly 172,000 people found that the same gene increased the risk of heart attack by 37 percent.
These findings jibe with those of previous studies regarding the heart health effects of testosterone, said Dr. Richard Becker, director of the University of Cincinnati’s Heart, Lung and Vascular Institute.
“One could conclude that the findings — although it’s not proof of cause and effect — certainly are consistent with some of the concerns that have been raised,” Becker said.
Men carrying this particular genetic mutation should be mindful of their heart health, he added.
“You would address all known and modifiable risk factors first, and you would probably do that as aggressively as you could,” Becker said. These men should exercise regularly, eat right, avoid smoking and watch their weight, blood pressure and blood sugar, he advised.
Further study is needed to determine if naturally high testosterone levels are a heart risk factor that should be directly treated, Becker added.
Beyond that, the study would indicate that older men should think twice before indulging in testosterone-replacement therapy, the experts noted.
Becker said that the U.S. Food and Drug Administration now requires testosterone product labels to warn of a possible increased risk of heart attack and stroke.
Testosterone is believed to contribute to hardening of the arteries, Becker added, and people taking large doses are more likely to form blood clots.
Mintz pointed out that “medical testosterone-replacement therapy has decreased over the last few years, but still remains at a significant level. These prescription requests are due to social pressures and a lack of education in this area.”
“Testosterone-replacement treatment is not sexy, but really dangerous if given to patients without a true medical indication and a known proven benefit,” Mintz concluded.
The new study was published online March 6 in the BMJ.
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SOURCES: Guy Mintz, M.D., director, cardiovascular health and lipidology, Northwell Health’s Sandra Atlas Bass Heart Hospital, Manhasset, N.Y.; Richard Becker, M.D., director, University of Cincinnati Heart, Lung and Vascular Institute; March 6, 2019, BMJ, online