Testosterone replacement is increasingly prescribed for older men with age-related declines in testosterone, particularly in the United States. The Food and Drug Administration has warned of the risk of heart attack and stroke on testosterone and requested a large randomized controlled trial to assess the cardiovascular effects of testosterone. No such trial is yet underway.

CUNY School of Public Health professor Dr. C. Mary Schooling and colleagues conducted a Mendelian Randomization study assessing the effects of testosterone and sex-hormone binding protein (SHBG) (using variants from the JMJD1C and SHBG gene regions) on coronary artery disease (CAD) in the CARDIoGRAMplusC4D consortium 1000 genomes case-control study (171,191 individuals including 60,801 cases), and on CAD and ischemic stroke risk in the UK Biobank (367,643 individuals including 25,352 CAD cases and 3650 ischemic stroke cases). The findings were published in the International Journal of Cardiology. The study found that testosterone, but not SHBG, likely increased the risk of ischemic heart disease and stroke, particularly for men.

“Testosterone increasing the risk of ischemic heart disease and stroke explains why men have substantially higher rates of these diseases than women,” Dr. Schooling says. “In fact, several of the most effective existing means of preventing heart disease and stroke reduce testosterone, such as statins, digoxin and spironolactone. Explicitly, targeting testosterone provides a timely new avenue for preventing ischemic heart disease and stroke at a time when the development of new preventative treatments targeting lipids and inflammation has delivered little despite very substantial investment.”

C.M. Schooling, et al., Genetic predictors of testosterone and their associations with cardiovascular disease and risk factors: A Mendelian randomization …, Int J Cardiol (2018)