Does intravenous (IV) testosterone use increase the risk of cardiac disease?

From the Guidelines

Intravenous testosterone administration is not a standard or approved method of testosterone replacement therapy and may increase the risk of cardiac disease. Testosterone therapy is typically administered via intramuscular injections, transdermal patches, gels, or pellets—never through IV routes. Using testosterone intravenously would cause dangerous spikes in hormone levels, potentially leading to serious cardiovascular complications including increased blood pressure, altered cholesterol levels, increased red blood cell production (polycythemia), and heightened risk of blood clots, heart attacks, and strokes. These rapid fluctuations in testosterone levels bypass the body's natural regulatory mechanisms and can place excessive strain on the cardiovascular system. Additionally, IV testosterone would have a very short half-life in the bloodstream, making it impractical for hormone replacement purposes. Some key points to consider include:

• The potential for increased cardiovascular risk with testosterone therapy, particularly in men with pre-existing cardiovascular disease 1
• The importance of proper medical supervision and monitoring of cardiovascular parameters, complete blood count, and hormone levels to ensure safety 1
• The lack of evidence supporting the use of IV testosterone for hormone replacement therapy, and the potential for serious adverse effects 1 If testosterone therapy is medically indicated, patients should only use FDA-approved formulations under proper medical supervision with regular monitoring of cardiovascular parameters, complete blood count, and hormone levels to ensure safety. It is essential to prioritize the patient's safety and well-being, and to carefully weigh the potential benefits and risks of testosterone therapy, particularly in men with pre-existing cardiovascular disease. The most recent and highest quality study on this topic is from 2020, which found that testosterone treatment in adult men with age-related low testosterone did not increase the risk of adverse cardiovascular events, but did improve vitality and fatigue 1. However, this study did not specifically address the use of IV testosterone, and the results should be interpreted with caution. In general, the use of IV testosterone is not recommended, and patients should be advised of the potential risks and benefits of testosterone therapy, and closely monitored for any adverse effects.

From the FDA Drug Label

5.5 Cardiovascular Risk

The FDA drug label mentions Cardiovascular Risk as a warning and precaution for testosterone use. However, it does not specifically address the risk of cardiac disease associated with intravenous (IV) testosterone use.

• The label does mention that testosterone can increase the risk of venous thromboembolism and polycythemia, which can be related to cardiovascular risk, but it does not provide direct information on the risk of cardiac disease with IV use.
• Given the lack of direct information, no conclusion can be drawn about the specific risk of cardiac disease with IV testosterone use 2.

From the Research

IV Testosterone Use and Cardiac Disease Risk

The relationship between intravenous (IV) testosterone use and the risk of cardiac disease is complex and has been the subject of numerous studies.

• The use of testosterone therapy in men with hypogonadism and cardiac disease has been shown to be safe when achieving physiological levels, with adequate monitoring of prostate-specific antigen and hematocrit levels during the course of treatment per established clinical guidelines 3.
• A multicenter, randomized, double-blind, placebo-controlled, noninferiority trial found that testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events in men with hypogonadism and preexisting or a high risk of cardiovascular disease 4.
• However, some studies have suggested that testosterone replacement therapy may increase the risk of cardiovascular disease, which has led to a warning statement from the FDA about the potential cardiovascular risks of testosterone replacement therapy 5.
• A retrospective national cohort study found that the use of testosterone therapy was associated with increased risk of adverse outcomes, including all-cause mortality, myocardial infarction, and stroke, among male veterans with low testosterone levels 6.
• A literature review found that the evidence on the cardiovascular safety of testosterone is limited and that a large, long-term, prospective, placebo-controlled, double-blind trial is needed to determine the safety of testosterone therapy 7.

Key Findings

• Testosterone therapy may have niche roles in certain conditions, such as advanced heart failure and cardiac cachexia 3.
• Testosterone-replacement therapy was found to be noninferior to placebo with respect to the incidence of major adverse cardiac events in men with hypogonadism and preexisting or a high risk of cardiovascular disease 4.
• The use of testosterone therapy was associated with increased risk of adverse outcomes, including all-cause mortality, myocardial infarction, and stroke, among male veterans with low testosterone levels 6.
• The evidence on the cardiovascular safety of testosterone is limited, and more research is needed to determine the safety of testosterone therapy 5, 7.