In January 2014, the Public Library of Science’s peer-reviewed scientific journal PLOS ONE published a study that found the risk of heart attack associated with testosterone therapy is substantially increased among older men and younger men with preexisting heart disease.
The PLOS ONE testosterone study compared the rate of heart attacks among men in the 90 days following a testosterone therapy drug prescription and the one year prior to the prescription. Using a large healthcare database, the PLOS ONE study investigated whether testosterone therapy might increase the risk of heart attack and whether this risk might be particularly strong where a patient has a preexisting heart condition.
The study compared patients with testosterone product prescriptions with those with erectile dysfunction drug prescriptions. The erectile dysfunction drug was chosen for the comparison population because it has similar indications to testosterone therapy. The study notes that there was no association found between the erectile dysfunction drug and an increased risk of heart attack.
The study identified diagnoses among patients associated with myocardial infarction (heart attack), including:
Because prior studies have indicated cardiovascular problems that may be associated with testosterone therapy arise early during treatment, the PLOS ONE study focused on the first 90 days after a patient receives a low-T prescription.
Among men aged 65 and older, the study found the risk of heart attack doubled in the 90 days after filing an initial testosterone therapy prescription. Among those who did not refill their testosterone therapy prescriptions, the risk of heart attack return to normal 91 to 180 days after initially receiving the prescription.
Among younger men with a prior history of heart problems, the study found a two to three-hold increased risk of heart attack during the first 90 days following an initial testosterone product prescription. The study did not find an excess risk among younger men with no prior cardiovascular problems. Among older men, the increased risk of heart attack was associated with testosterone replacement therapy regardless of whether the older men had histories of heart disease.
The medical investigation noted that it was limited because the healthcare database did not include information on serologic or diagnostic indications for treatment. The database also only identified patients with non-fatal heart attacks and was based on information provided by the attending physician, rather than a structured evaluation that might occur in a larger trial.
The PLOS ONE study reported that its findings were “consistent with a recent meta-analysis of placebo-controlled randomized trials of testosterone therapy…which reported that testosterone therapy increased the risk of adverse cardiovascular-related events, as well as serious adverse cardiovascular-related events which included [heart attacks] along with other conditions.” Testosterone therapy, the PLOS ONE study found, is associated with physical changes that can lead to clotting and thrombotic disorders, including increased blood pressure and reductions in HDL cholesterol.
The testosterone study advises that further investigation is needed to examine the risk of stroke, heart attack, and death with low-T drugs. The increased risk of heart attack among young men with prior heart disease is a “particular public health concern, as about 10 percent of the men in our study under age 65 years with a [testosterone therapy] prescription had a history of heart disease.”