Testosterone Replacement Therapy in Hypogonadal Men and Myocardial Infarction Risk: Systematic Review & Meta-Analysis

Testosterone replacement therapy (TRT) has become increasingly popular over the years and there has been an increasing debate on whether testosterone replacement should be offered to older men due to its association with cardiovascular events. In this study, we evaluated the risk of myocardial infarction (MI) associated with TRT in hypogonadal men through a meta-analysis. We carried out the analysis by following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: Google Scholar, PubMed, Science Direct, Cochrane Library trials, and ClinicalTrials.gov. The search strategy resulted in a total of 782 articles, after applying our inclusion and exclusion criteria. Six observational studies and two randomized controlled trials (RCTs) were included for the analysis. A total of 55,806 hypogonadal men with baseline testosterone levels <300ng/mL were included in the analysis. The intervention group received testosterone in various routes including transdermal patches, gels, mouth patches, testosterone injections, and deposits. The incidence of MI was taken to be the primary measure outcomes. The pooled data from eight studies showed MI incidence in 249 out of 11,720 (2.1%) in the TRT group and 1420 out of 33,086 (4.3%) in the control group. The pooled OD showed no statistically significant association of TRT and MI compared to the control group (OR = 0.76, 95% CI 0.36-1.31; p=0.48). The model revealed high heterogeneity with I(2) =79%. With sensitivity analysis and, excluding two studies out of the eight, the pooled data was able to achieve low heterogeneity with I(2) = 0%. The newly pooled data from six studies showed MI incidence in 226 out of 10,137 (2.2%) in the TRT group and 969 out of 36,304 (2.7%) in the control group. The pooled OD shows no statistical significance in the association between TRT treatment and MI compared to the control group. (OR =0.87, 95% CI 0.75-1.01; P =0.08). It appears that TRT does not increase the risk of MI as compared to the non-intervention group. Further RCTs with greater population size are needed that could produce more solid results, allowing more definitive conclusions to be made on this topic.