madman
Super Moderator
ABSTRACT
Background
The Cardiovascular safety of testosterone replacement therapy (TRT) among men with hypogonadism is not well established to date. Hence, we sought to evaluate the cardiovascular disease (CVD) outcomes among patients receiving testosterone therapy by using all recently published randomized controlled trials.
Methods
We performed a systematic literature search on PubMed, EMBASE, and Clinicalirial.gov for relevant randomized controlled trials (RCTs) from inception until September 30th, 2023.
Results
A total of 30 randomized trials with 11,502 patients were included in the final analysis. The mean age was ranging from 61.61 to 61.82 years, Pooled analysis of primary and secondary outcomes showed that the incidence of any CVD events (OR, 1.12 (95%CI: 0.77-1.62), P = 0.55), stroke (OR, 1.01 (95%CI: 0.68-1.51), P =0.94), myocardial infarction (OR, 1.05 (95%CI: 0.76-1.45), P = 0.77), all-cause mortality (OR, 0.94 (95%CI:0.76-1.17), P = 0.57), and CVD mortality (OR, 0.87 (95%CI: 0.65-1.15), P = 0.31) was comparable between TRT and placebo groups.
Conclusion
Our analysis indicates that for patients with hypogonadism, testosterone replacement therapy does not increase the CVD risk and all-cause mortality.
Introduction
Testosterone replacement therapy (TRT) is commonly used in patients with hypogonadism, often in elderly men who are >50 years old.' Nevertheless, not all individuals with reduced testosterone levels exhibit symptoms.’ For those who do, these symptoms can encompass impairments in sexual and physical functions.’ In addition, obesity, type 2 diabetes mellitus, metabolic syndrome, and cognitive dysfunction are associated with testosterone deficiency (TD). These conditions are widely acknowledged cardiovascular (CV) disease (CVD) risk factors, and with their increased prevalence in patients with TD, it is believed that these patients are at increased CVD risk.°'
Various studies reported poor CV health in those with TD with increased CVD events, including myocardial infarction symptoms, (MI) and stroke. With the indication of TRT for hypogonadism symptoms, such as erectile dysfunction and decreased muscle mass, it seems logical that normalizing testosterone levels with supplementation alleviates some of the adverse events.’ However, conflicting results were reported in retrospective cohort studies and randomized clinical trials (RCTs) of patients receiving TRT and with anabolic steroid abuse.’ '” In March 2015, the Food and Drug Administration (FDA) issued a drug safety communication cautioning about the use of products containing testosterone and highlighting a potential rise in CVD events.
In light of the growing utilization of TRT among individuals with TD in recent years, conflicting results from previous studies, and increased reports of CVD events in those with anabolic steroid abuse, the impact of testosterone on CV health remains a subject of ongoing debate. Hence, we sought to perform an updated meta-analysis evaluating the safety of TRT and CVD outcomes among patients with hypogonadism.
Strengths and Limitations
This meta-analysis included 30 RCTs to evaluate the CV safety of TRT, giving a most comprehensive and robust assessment. There were limitations worth mentioning, including the fact that the RCTs have varying study designs, different races and ethnicities, and endpoints. Hence, a potential for inherent heterogeneity is possible. Different follow-ups are being used to evaluate the outcomes. Hence, a possible fluctuation among the events may be present.
Conclusion
Our analysis indicates that for patients with hypogonadism, TRT does not appear to increase the CVD risk and all-cause mortality (Graphical Abstract). Further, large power multicenter RCTs are needed to strengthen the evidence available by including participants with varying baseline CVD and race and possibly higher levels of on-treatment testosterone levels.
Background
The Cardiovascular safety of testosterone replacement therapy (TRT) among men with hypogonadism is not well established to date. Hence, we sought to evaluate the cardiovascular disease (CVD) outcomes among patients receiving testosterone therapy by using all recently published randomized controlled trials.
Methods
We performed a systematic literature search on PubMed, EMBASE, and Clinicalirial.gov for relevant randomized controlled trials (RCTs) from inception until September 30th, 2023.
Results
A total of 30 randomized trials with 11,502 patients were included in the final analysis. The mean age was ranging from 61.61 to 61.82 years, Pooled analysis of primary and secondary outcomes showed that the incidence of any CVD events (OR, 1.12 (95%CI: 0.77-1.62), P = 0.55), stroke (OR, 1.01 (95%CI: 0.68-1.51), P =0.94), myocardial infarction (OR, 1.05 (95%CI: 0.76-1.45), P = 0.77), all-cause mortality (OR, 0.94 (95%CI:0.76-1.17), P = 0.57), and CVD mortality (OR, 0.87 (95%CI: 0.65-1.15), P = 0.31) was comparable between TRT and placebo groups.
Conclusion
Our analysis indicates that for patients with hypogonadism, testosterone replacement therapy does not increase the CVD risk and all-cause mortality.
Introduction
Testosterone replacement therapy (TRT) is commonly used in patients with hypogonadism, often in elderly men who are >50 years old.' Nevertheless, not all individuals with reduced testosterone levels exhibit symptoms.’ For those who do, these symptoms can encompass impairments in sexual and physical functions.’ In addition, obesity, type 2 diabetes mellitus, metabolic syndrome, and cognitive dysfunction are associated with testosterone deficiency (TD). These conditions are widely acknowledged cardiovascular (CV) disease (CVD) risk factors, and with their increased prevalence in patients with TD, it is believed that these patients are at increased CVD risk.°'
Various studies reported poor CV health in those with TD with increased CVD events, including myocardial infarction symptoms, (MI) and stroke. With the indication of TRT for hypogonadism symptoms, such as erectile dysfunction and decreased muscle mass, it seems logical that normalizing testosterone levels with supplementation alleviates some of the adverse events.’ However, conflicting results were reported in retrospective cohort studies and randomized clinical trials (RCTs) of patients receiving TRT and with anabolic steroid abuse.’ '” In March 2015, the Food and Drug Administration (FDA) issued a drug safety communication cautioning about the use of products containing testosterone and highlighting a potential rise in CVD events.
In light of the growing utilization of TRT among individuals with TD in recent years, conflicting results from previous studies, and increased reports of CVD events in those with anabolic steroid abuse, the impact of testosterone on CV health remains a subject of ongoing debate. Hence, we sought to perform an updated meta-analysis evaluating the safety of TRT and CVD outcomes among patients with hypogonadism.
Strengths and Limitations
This meta-analysis included 30 RCTs to evaluate the CV safety of TRT, giving a most comprehensive and robust assessment. There were limitations worth mentioning, including the fact that the RCTs have varying study designs, different races and ethnicities, and endpoints. Hence, a potential for inherent heterogeneity is possible. Different follow-ups are being used to evaluate the outcomes. Hence, a possible fluctuation among the events may be present.
Conclusion
Our analysis indicates that for patients with hypogonadism, TRT does not appear to increase the CVD risk and all-cause mortality (Graphical Abstract). Further, large power multicenter RCTs are needed to strengthen the evidence available by including participants with varying baseline CVD and race and possibly higher levels of on-treatment testosterone levels.
