Does Testosterone Replacement Therapy (TRT) benefit the cardiovascular system?

From the Guidelines

Testosterone Replacement Therapy (TRT) may have a neutral or potentially beneficial effect on the cardiovascular system, as suggested by existing evidence, including a study published in the New England Journal of Medicine 1 and more recent guidelines from the American College of Physicians 1.

Key Considerations

• The impact of TRT on cardiovascular health can vary based on the patient's baseline health status, dose, and formulation of testosterone used.
• Properly administered TRT may offer cardiovascular benefits, including improved insulin sensitivity, reduced body fat, increased lean muscle mass, and better lipid profiles.
• However, TRT may increase the risk of cardiovascular events in older men with pre-existing heart disease, potentially raising hematocrit levels and blood pressure.

Recommendations

• Men considering TRT should undergo comprehensive cardiovascular risk assessment before starting treatment.
• Regular monitoring of hematocrit, blood pressure, lipid profiles, and PSA levels is recommended during therapy.
• The ideal approach involves individualizing treatment based on specific health conditions, using the lowest effective dose, and maintaining testosterone levels within physiological ranges to maximize benefits while minimizing cardiovascular risks.

Formulations and Dosage

• Common TRT formulations include injectable testosterone cypionate (50-200mg every 1-2 weeks), testosterone enanthate (similar dosing), daily transdermal gels (AndroGel, Testim at 50-100mg), or pellet implants (lasting 3-6 months).
• The choice of formulation and dosage should be based on the patient's specific needs and health status, as well as consideration of potential benefits and risks.

Evidence Base

• The evidence base for TRT and cardiovascular health is mixed, with some studies suggesting potential benefits and others indicating potential risks.
• Recent guidelines from the American College of Physicians 1 provide a comprehensive review of the evidence and recommendations for clinical practice.
• A study published in the New England Journal of Medicine 1 found that TRT may have a neutral or potentially beneficial effect on the cardiovascular system, although the evidence is not yet conclusive.

From the FDA Drug Label

1. 5 Cardiovascular Risk Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men.

The FDA drug label does not answer the question of whether TRT benefits the cardiovascular system. In fact, it highlights the uncertainty and potential risks associated with testosterone replacement therapy, stating that long-term clinical safety trials have not been conducted to assess cardiovascular outcomes and that epidemiologic studies and randomized controlled trials have been inconclusive. Therefore, no conclusion can be drawn about the benefits of TRT on the cardiovascular system based on the provided drug label information 2.

From the Research

Cardiovascular Effects of Testosterone Replacement Therapy (TRT)

The relationship between TRT and its effects on the cardiovascular system is complex and has been the subject of numerous studies. Some key points to consider include:

• The potential risks associated with TRT, particularly in relation to cardiovascular events, are still not well established and require further investigation 3, 4, 5.
• Some studies suggest that TRT may increase the risk of cardiovascular events, such as ischemic stroke, transient ischemic attack, and myocardial infarction, particularly in the first 2 years of use 4.
• However, other studies have found no significant association between TRT and adverse cardiovascular events, especially when hypogonadism is properly diagnosed and replacement therapy is correctly performed 6, 7.
• The FDA has released a warning statement about the potential cardiovascular risks of testosterone replacement therapy, but the cardiovascular safety of this therapy remains unclear 5.

Key Findings

Some key findings from the studies include:

• A cohort study of 15,401 men found that current use of TRT was associated with an increased risk of cardiovascular events, particularly in the first 6 months to 2 years of continuous use 4.
• A review of epidemiological data and randomized trials found that the association between serum levels of endogenous testosterone and cardiovascular disease is unclear, and that the cardiovascular safety of TRT remains uncertain 5.
• A meta-analysis of randomized controlled studies and observational investigations found no causal role between TRT and adverse cardiovascular events, especially when hypogonadism is properly diagnosed and replacement therapy is correctly performed 7.

Considerations for TRT Use

When considering TRT, it is essential to:

• Properly diagnose hypogonadism and ensure that replacement therapy is correctly performed 6, 7.
• Discuss potential risks with patients and monitor them regularly to minimize side effects 3, 4.
• Be cautious when prescribing TRT, particularly in aging men with low testosterone levels, and consider the potential risks and benefits 4, 5.