What are the cardiovascular effects of Testosterone Replacement Therapy (TRT)?

From the Guidelines

Testosterone replacement therapy does not appear to have a significant harmful effect on the heart, with the most recent and highest quality study suggesting a neutral or possibly beneficial effect on cardiovascular disease. According to the study by 1, the pooled risk for adverse cardiovascular outcomes did not differ between groups, with a Peto OR of 1.22 (CI, 0.66 to 2.23) and low-certainty evidence. The incidence of cardiovascular events was 2.3% (CI, 0.9% to 4.1%) in the testosterone group, compared with 1.5% (CI, 0.8% to 2.5%) in the placebo group.

Some potential benefits of testosterone replacement therapy on the heart include:

• Increased angina-free exercise tolerance in men with chronic stable angina, as found by English et al. in the study 1
• Improved coronary-artery diameter and blood flow, as observed in a study where physiologic levels of testosterone were directly injected into the coronary arteries 1
• A possible beneficial effect on lipid profiles, with numerous controlled studies showing no change or only a minimal reduction in HDL, often accompanied by a reduction in total cholesterol 1

However, it is essential to note that:

• Testosterone replacement therapy may increase the risk of erythrocytosis, which can lead to thickened blood and strain the heart 1
• The risk of cardiovascular events may be higher in older men and those with established cardiovascular disease
• Men on TRT should have regular monitoring of hematocrit levels, blood pressure, and lipid profiles, and those with cardiovascular risk factors should discuss these concerns thoroughly with their healthcare provider before starting treatment.

In terms of specific monitoring and management, the study by 1 suggests that:

• Erythrocytosis is a potential risk, with a wide range of risk depending on the mode of administration, and requires monitoring
• Lipid profiles should be monitored, as the effects of testosterone replacement therapy on lipids are inconsistent
• Blood pressure should be monitored, as testosterone may affect blood pressure levels.

From the FDA Drug Label

There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as testosterone enanthate injection. 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. Due to sodium and water retention, edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease

The harmful effects of testosterone replacement on the heart include:

• Venous thromboembolic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Major adverse cardiovascular events (MACE), including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, although the evidence is inconclusive
• Edema with or without congestive heart failure, particularly in patients with preexisting cardiac, renal, or hepatic disease 2

From the Research

Harmful Effects of Testosterone Replacement on the Heart

• The current evidence on the harmful effects of testosterone replacement therapy (TRT) on the heart is mixed and often contradictory 3, 4, 5, 6, 7.
• Some studies suggest that TRT may increase the risk of cardiovascular disease, particularly in elderly men or those with pre-existing cardiovascular conditions 4, 7.
• However, other studies have found that TRT may have a beneficial or neutral effect on cardiovascular risk, particularly when used to achieve physiologic testosterone concentrations in hypogonadal men 3, 5, 6.
• The use of TRT has been shown to improve myocardial ischemia in men with coronary artery disease, improve exercise capacity in patients with congestive heart failure, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes 5.
• A recent review found that TRT in hypogonadal men can improve many cardiovascular disease risk factors, reduce QT interval prolongation, lead to better outcomes in heart failure patients, and slow the progression of atherosclerosis 6.

Key Findings

• Hypogonadism is associated with increased mortality in men with cardiovascular disease, and TRT may have a cardioprotective effect in these men 6.
• The cardiovascular safety of TRT remains unclear, and more research is needed to fully understand its effects on the heart 4, 7.
• Testosterone replacement therapy should be used with caution in older patients and those who are susceptible to cardiovascular diseases, as they may be at increased risk of adverse cardiovascular events 7.