In the latest addition to the ongoing debate over the safety of testosterone treatment, researchers report no significant increased heart-attack risk in older men treated with an intramuscular form of the therapy.
The study, published online this week in the Annals of Pharmacotherapy, compared 6355 Medicare beneficiaries treated with testosterone with 19,065 who were not, between January 1997 and December 2005, and showed no increased risk of myocardial infarction (MI) in the treatment group (hazard ratio [HR], 0.84; 95 percent confidence interval [CI], 0.69 – 1.02).
"In this matched double-cohort study of more than 24,000 Medicare beneficiaries, we found that use of intramuscular testosterone therapy was not associated with an increased risk of MI," say the authors.
Furthermore, "a dose–response analysis demonstrated no increased risk in MI according to estimated cumulative dose of testosterone. These findings were robust across a range of sensitivity analyses that addressed eligibility criteria, exposure thresholds, follow-up periods, and covariate adjustment," they add.
In fact, testosterone was associated with a possible protective effect — a reduced risk of heart attack in patients with the highest prognostic risk index for MI (HR, 0.69; 95 percent CI, 0.53 – 0.92), and there were no differences in risk in patients in the lower quartiles of MI prognostic score.
First author Jacques Baillargeon, PhD, of the University of Texas Medical Branch in Galveston, noted that various potential mechanisms could explain the protective effect. "Certainly there is some literature showing plausible biologic mechanisms where testosterone could in theory confer a protective effect, such as by decreasing fat mass, increasing lean body mass, and decreasing insulin sensitivity and the lipid profile," he told Medscape Medical News.
"Testosterone may also possess anti-inflammatory and anticoagulant properties, but likewise, there are also plausible pathways whereby it could increase cardiovascular risk, so there are arguments to be made both ways," he said.
No Increased MI Risk With Intramuscular Testosterone "Reassuring"
Patients in the study were over aged 65, and testosterone-treated patients were matched 1:3 with nontreated patients according to their composite MI prognostic index score.
Reasons for initiation of testosterone therapy included hypogonadism, sexual dysfunction, fatigue, and osteoporosis.
The men were followed until December 2005 or they lost their Medicare coverage, experienced an MI, or died. Those receiving testosterone therapy had an average follow-up of 1495 days; the average follow-up for those not receiving therapy was 1193 days.
Because the treatments were all given before 2005, testosterone was administered in the form of intramuscular injections. Patients receiving the therapy had an average of 8.2 injections over the study period, including 4.4 injections in the first year, and were more likely to have a high degree of comorbid disease compared with nonusers.