New York—Men who use testosterone supplements to boost energy levels and sex drive may inadvertently increase their risk for cardiovascular events, suggests a new study that primarily looked at those with a genetic predisposition to high levels of the hormone.
The research, published in BMJ, raises the possibility that elevated testosterone levels play a role in the development of major heart problems in men. Whether that occurs with supplementation has been hinted at in past studies, and the authors of this study consider data supportive of those results.
The international study team, led by researchers from the City University of New York's Graduate School of Public Health & Health Policy and the University of Hong Kong, used Mendelian randomization to analyze genetic variants that predict testosterone levels and their associations with thromboembolism, heart failure, and myocardial infarction in nearly 400,000 men and women from a large genome study and the United Kingdom Biobank database.
Study participants ranged from 40 to 75 years old, with most being of British or European ancestry. Cardiovascular conditions were identified from self-reports and hospital and death records, and results were validated using data from another large genome study.
The authors point out that their method of analyzing genetic information avoids some of the problems in traditional observational studies, making the results less prone to confounding factors. In fact, they note, an association that is observed using Mendelian randomization actually strengthens the inference of a causal relationship.
Results indicate that, of the UK Biobank participants, 13,691 had thromboembolism (6,208 men, 7,483 women); 1,688 had heart failure (1,186 men and 502 women); and 12,882 had myocardial infarction (10,136 men and 2,746 women). In men, the study authors emphasize, endogenous testosterone genetically predicted by variants in the JMJD1C gene region was positively associated with thromboembolism (odds ratio per unit increase in log transformed testosterone ([nmol/L]) 2.09, 95% confidence interval [CI] 1.27-3.46) and heart failure (7.81; 95% CI, 2.56-23.8), but not myocardial infarction (1.17; 95% CI, 0.78-1.75).
Associations were less clear for women, according to the researchers, although genetically predicted testosterone (based on JMJD1C gene region variants) was positively associated with myocardial infarction (1.37; 95% CI, 1.03-1.82).
“Endogenous testosterone was positively associated with thromboembolism, heart failure, and myocardial infarction in men,” the study authors conclude. “Rates of these conditions are higher in men than women. Endogenous testosterone can be controlled with existing treatments and could be a modifiable risk factor for thromboembolism and heart failure.”
The article notes, “Testosterone sales increased 12-fold globally from 2000 to 2011, with noticeable increases in North America. In the United States, older men have probably been targeted in addition to men requiring medically indicated treatment for low testosterone levels. Testosterone replacement therapy (TRT) prescriptions in the US decreased by 50% between 2013 and 2016, but remain well above the levels needed to treat pathological hypogonadism.”
Also noted is that, since the 1970s, use of anabolic steroids has spread from athletes to the general population, with a lifetime prevalence rate of 6.4% for men.
“From a clinical perspective, our study suggests that lifelong endogenous testosterone could have a role in thromboembolism, heart failure, and possibly myocardial infarction, particularly among men,” the researchers add. “These findings provide another strand of evidence consistent with the cardiovascular warnings about TRT issued by regulators.
"Further evidence is needed to clarify whether our findings are relevant to the higher rates of these diseases in men than in women, or suggest that agents that lower testosterone would be protective. Additional research is also required comparing the effects of endogenous testosterone with those of exogenous testosterone.”
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The research, published in BMJ, raises the possibility that elevated testosterone levels play a role in the development of major heart problems in men. Whether that occurs with supplementation has been hinted at in past studies, and the authors of this study consider data supportive of those results.
The international study team, led by researchers from the City University of New York's Graduate School of Public Health & Health Policy and the University of Hong Kong, used Mendelian randomization to analyze genetic variants that predict testosterone levels and their associations with thromboembolism, heart failure, and myocardial infarction in nearly 400,000 men and women from a large genome study and the United Kingdom Biobank database.
Study participants ranged from 40 to 75 years old, with most being of British or European ancestry. Cardiovascular conditions were identified from self-reports and hospital and death records, and results were validated using data from another large genome study.
The authors point out that their method of analyzing genetic information avoids some of the problems in traditional observational studies, making the results less prone to confounding factors. In fact, they note, an association that is observed using Mendelian randomization actually strengthens the inference of a causal relationship.
Results indicate that, of the UK Biobank participants, 13,691 had thromboembolism (6,208 men, 7,483 women); 1,688 had heart failure (1,186 men and 502 women); and 12,882 had myocardial infarction (10,136 men and 2,746 women). In men, the study authors emphasize, endogenous testosterone genetically predicted by variants in the JMJD1C gene region was positively associated with thromboembolism (odds ratio per unit increase in log transformed testosterone ([nmol/L]) 2.09, 95% confidence interval [CI] 1.27-3.46) and heart failure (7.81; 95% CI, 2.56-23.8), but not myocardial infarction (1.17; 95% CI, 0.78-1.75).
Associations were less clear for women, according to the researchers, although genetically predicted testosterone (based on JMJD1C gene region variants) was positively associated with myocardial infarction (1.37; 95% CI, 1.03-1.82).
“Endogenous testosterone was positively associated with thromboembolism, heart failure, and myocardial infarction in men,” the study authors conclude. “Rates of these conditions are higher in men than women. Endogenous testosterone can be controlled with existing treatments and could be a modifiable risk factor for thromboembolism and heart failure.”
The article notes, “Testosterone sales increased 12-fold globally from 2000 to 2011, with noticeable increases in North America. In the United States, older men have probably been targeted in addition to men requiring medically indicated treatment for low testosterone levels. Testosterone replacement therapy (TRT) prescriptions in the US decreased by 50% between 2013 and 2016, but remain well above the levels needed to treat pathological hypogonadism.”
Also noted is that, since the 1970s, use of anabolic steroids has spread from athletes to the general population, with a lifetime prevalence rate of 6.4% for men.
“From a clinical perspective, our study suggests that lifelong endogenous testosterone could have a role in thromboembolism, heart failure, and possibly myocardial infarction, particularly among men,” the researchers add. “These findings provide another strand of evidence consistent with the cardiovascular warnings about TRT issued by regulators.
"Further evidence is needed to clarify whether our findings are relevant to the higher rates of these diseases in men than in women, or suggest that agents that lower testosterone would be protective. Additional research is also required comparing the effects of endogenous testosterone with those of exogenous testosterone.”
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