Is transdermal testosterone replacement safe in men with known heart disease or at high risk for heart disease?
Although the most serious cardiovascular events were not more common in this group of high-risk men using testosterone gel, there were higher incidence rates of acute kidney injury, atrial fibrillation, nonfatal arrhythmias, and pulmonary embolism. Testosterone supplementation should be used with caution, if at all, in men with a history of these conditions.
Plan de l'etude:
Randomized controlled trial (double-blinded)
The data regarding the safety of testosterone supplementation have been mixed, with some studies finding increased cardiovascular (CV) risk. The United States Food and Drug Administration therefore mandated that companies that sell these supplements perform a safety study. These researchers identified men, aged 45 to 80 years, with symptoms of hypogonadism and 2 fasting morning serum testosterone levels of less than 300 ng/dL. All the patients had pre-existing CV disease (55%) or were at increased risk of CV disease (45%). The patients were randomized to receive testosterone gel titrated to achieve a level between 350 and 750 ng/dL or matching placebo gel with sham titrations. The testosterone was discontinued if the patient's serum level exceeded 750 ng/dL even at the lowest dose, or if the hematocrit level exceeded 54%. Groups were balanced at baseline, with a mean age of 63 years, and high percentages being White (80%) and having diabetes mellitus (69%), hypertension (93%), or hyperlipidemia (90%). Analysis was by intention to treat. The full study population included 5204 patients, with 5198 receiving at least one dose of the drug and being included in the safety population for the primary analysis. Patients were treated for a mean of approximately 22 months and followed up for a mean of 33 months. There was no difference between groups in the primary safety outcome of major adverse cardiac events, which included CV death, nonfatal myocardial infarction, and nonfatal stroke (7.0% vs 7.3%). There was also no difference for any of the components of the composite outcome, all-cause mortality, need for revascularization, or need for hospitalization. The authors did see an increase in the risk of nonfatal arrhythmia warranting an intervention (5.2% vs 3.0%; P = .001; number needed to treat to harm [NNTH] = 45 over 21 months), atrial fibrillation (3.5% vs 2.4%; P = .02; NNTH = 91 over 21 months), and acute kidney injury (2.3% vs 1.5%; P = .04; NNTH = 125 over 21 months). Improvement in symptoms was not reported. Pulmonary emboli were also more common (0.92% vs 0.46%). The authors did not report statistical significance for this outcome, but I checked a Fisher's exact test and found P = .046.
Mark H. Ebell, MD, MS
University of Georgia