Introduction
Background and significance
Hypogonadism, characterized by low testosterone levels, is a significant clinical condition affecting a substantial proportion of the male population, particularly older men. The management of hypogonadism often involves testosterone replacement therapy (TRT), which can be administered through various routes, including intramuscular injections, transdermal patches, and oral formulations. While injectable and transdermal options have been extensively studied, oral testosterone therapy, particularly using testosterone undecanoate (TU), has garnered increasing interest due to its non-invasive nature and ease of administration.
Objectives
This systematic review and meta-analysis aim to synthesize the current evidence on the safety and efficacy of oral testosterone therapy in hypogonadal men, with a primary focus on cardiovascular safety, liver toxicity, and prostate safety. Secondary objectives include assessing the impact of oral testosterone on bone mass, cardiovascular health, cognitive function, and mortality.
Primary outcomes: safety of oral testosterone therapy
▪ Cardiovascular risks
▪ Liver toxicity
▪ Prostate safety
Secondary outcomes: efficacy of oral testosterone therapy
▪ Bone mass
▪ Cardiovascular benefits
▪ Cognitive function
▪ Mortality reduction
Discussion
Interpretation of findings
The findings from this meta-analysis suggest that oral testosterone therapy is a safe and effective option for treating hypogonadism in men, with a safety profile comparable to other TRT forms. The absence of significant liver toxicity and minimal cardiovascular risks makes oral testosterone a viable alternative for men who prefer non-invasive treatment options. Studies have consistently shown that oral testosterone therapy does not significantly increase the risk of MACE or liver toxicity, offering a safety profile that is comparable to other forms of testosterone therapy [1,4].
Additionally, the small but statistically significant increase in SBP observed in some studies should be monitored,especially in patients with pre-existing cardiovascular conditions [3, 5]. In terms of prostate safety, minor increases in PSA levels were noted, but no significant increase in the risk of prostate cancer was observed, indicating a comparable safety profile for prostate health [6, 7, 9].
Clinical implications
Clinicians should consider oral testosterone therapy as a potential treatment option for hypogonadal men, particularly for those who are concerned about the invasiveness of injectable or transdermal testosterone therapies. Given the favorable safety profile, oral testosterone offers a less invasive alternative without compromising efficacy [8, 11].
However, it is recommended that clinicians regularly monitor cardiovascular health and prostate safety in patients undergoing oral testosterone therapy, especially in men with pre-existing conditions such as hypertension or prostate issues. Monitoring should include regular blood pressure checks, PSA level assessments, and evaluations for any cardiovascular events [1, 10]. Careful patient selection and follow-up will help ensure that the benefits of oral testosterone therapy are maximized while minimizing potential risks.
Limitations and Future Research
This meta-analysis is limited by the variability in study designs and the relatively short follow-up periods of some studies. Further long-term studies are necessary to fully understand the potential benefits and risks of oral testosterone, particularly regarding mortality and long-term cardiovascular outcomes (Figure 4).
Conclusion
Oral testosterone therapy is a promising treatment option for hypogonadal men, demonstrating a favorable safety and efficacy profile. While it offers potential benefits in terms of bone health and cognitive function, clinicians must remain vigilant in monitoring for cardiovascular and prostate-related risks. The current evidence supports the use of oral testosterone as a safe alternative to traditional TRT forms, though further research is warranted to confirm its long-term benefits and safety.
Background and significance
Hypogonadism, characterized by low testosterone levels, is a significant clinical condition affecting a substantial proportion of the male population, particularly older men. The management of hypogonadism often involves testosterone replacement therapy (TRT), which can be administered through various routes, including intramuscular injections, transdermal patches, and oral formulations. While injectable and transdermal options have been extensively studied, oral testosterone therapy, particularly using testosterone undecanoate (TU), has garnered increasing interest due to its non-invasive nature and ease of administration.
Objectives
This systematic review and meta-analysis aim to synthesize the current evidence on the safety and efficacy of oral testosterone therapy in hypogonadal men, with a primary focus on cardiovascular safety, liver toxicity, and prostate safety. Secondary objectives include assessing the impact of oral testosterone on bone mass, cardiovascular health, cognitive function, and mortality.
Primary outcomes: safety of oral testosterone therapy
▪ Cardiovascular risks
▪ Liver toxicity
▪ Prostate safety
Secondary outcomes: efficacy of oral testosterone therapy
▪ Bone mass
▪ Cardiovascular benefits
▪ Cognitive function
▪ Mortality reduction
Discussion
Interpretation of findings
The findings from this meta-analysis suggest that oral testosterone therapy is a safe and effective option for treating hypogonadism in men, with a safety profile comparable to other TRT forms. The absence of significant liver toxicity and minimal cardiovascular risks makes oral testosterone a viable alternative for men who prefer non-invasive treatment options. Studies have consistently shown that oral testosterone therapy does not significantly increase the risk of MACE or liver toxicity, offering a safety profile that is comparable to other forms of testosterone therapy [1,4].
Additionally, the small but statistically significant increase in SBP observed in some studies should be monitored,especially in patients with pre-existing cardiovascular conditions [3, 5]. In terms of prostate safety, minor increases in PSA levels were noted, but no significant increase in the risk of prostate cancer was observed, indicating a comparable safety profile for prostate health [6, 7, 9].
Clinical implications
Clinicians should consider oral testosterone therapy as a potential treatment option for hypogonadal men, particularly for those who are concerned about the invasiveness of injectable or transdermal testosterone therapies. Given the favorable safety profile, oral testosterone offers a less invasive alternative without compromising efficacy [8, 11].
However, it is recommended that clinicians regularly monitor cardiovascular health and prostate safety in patients undergoing oral testosterone therapy, especially in men with pre-existing conditions such as hypertension or prostate issues. Monitoring should include regular blood pressure checks, PSA level assessments, and evaluations for any cardiovascular events [1, 10]. Careful patient selection and follow-up will help ensure that the benefits of oral testosterone therapy are maximized while minimizing potential risks.
Limitations and Future Research
This meta-analysis is limited by the variability in study designs and the relatively short follow-up periods of some studies. Further long-term studies are necessary to fully understand the potential benefits and risks of oral testosterone, particularly regarding mortality and long-term cardiovascular outcomes (Figure 4).
Conclusion
Oral testosterone therapy is a promising treatment option for hypogonadal men, demonstrating a favorable safety and efficacy profile. While it offers potential benefits in terms of bone health and cognitive function, clinicians must remain vigilant in monitoring for cardiovascular and prostate-related risks. The current evidence supports the use of oral testosterone as a safe alternative to traditional TRT forms, though further research is warranted to confirm its long-term benefits and safety.
