Testosterone replacement therapy (TRT) is used to treat hypogonadism, a condition characterized by low testosterone levels and specific symptoms. Hypogonadism is prevalent, particularly among men with existing cardiovascular disease (CVD), where the incidence of low testosterone is significantly higher than in the general population. TRT restores testosterone levels to a normal range, improving symptoms like low libido, reduced energy, and decreased muscle mass. The primary question for patients and clinicians is whether this therapy is safe for individuals with a pre-existing heart condition.
The Historical Controversy Surrounding Testosterone Therapy
The idea of a heart risk associated with TRT gained traction in the early 2010s following several retrospective analyses and observational studies. These reports, often involving older men, suggested a possible link between the use of exogenous testosterone and an increased incidence of Major Adverse Cardiovascular Events (MACE).
Concerns were amplified by other studies that were criticized for methodological flaws, such as not adequately screening patients for pre-existing cardiac conditions or confirming true hypogonadism. This conflicting data led to significant public and regulatory concern. In 2015, the U.S. Food and Drug Administration (FDA) responded by requiring manufacturers to update the labeling on all approved testosterone products. This change included a warning about a possible increased risk of heart attack and stroke associated with TRT, fundamentally altering the drug’s safety perception for years.
Current Medical Consensus on Cardiovascular Safety
The historical controversy prompted the need for large-scale, rigorous research, culminating in the TRAVERSE trial. This landmark study was a randomized, placebo-controlled trial involving over 5,200 men with documented hypogonadism and either pre-existing cardiovascular disease or multiple risk factors. The goal was to definitively assess the cardiovascular safety of TRT.
The trial’s 2023 results demonstrated that TRT was noninferior to placebo concerning the incidence of MACE (Major Adverse Cardiovascular Events), which includes cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The rates of a first MACE event were statistically similar between the testosterone and placebo groups over a mean follow-up of 33 months. This provides robust evidence that, for appropriately screened hypogonadal men, TRT does not increase the overall risk of these severe cardiovascular outcomes.
Based on this data, the FDA updated the labeling for testosterone products in 2025, removing the language about an increased risk of heart attack and stroke from the Boxed Warning. This reflects the current clinical understanding that the previously feared broad cardiovascular risk is unsupported. However, the TRAVERSE trial did note a statistically higher incidence of specific adverse events, including non-fatal arrhythmias (like atrial fibrillation) and venous thromboembolic events (VTE), such as pulmonary embolism.
Physiological Mechanisms: How Testosterone Interacts with the Heart
Testosterone influences the cardiovascular system through several distinct physiological pathways, some beneficial and others requiring careful monitoring. On the positive side, testosterone acts as a vasodilator, meaning it helps relax and widen blood vessels. This effect is thought to occur rapidly and independently of the vessel lining.
Testosterone may also contribute to a healthier metabolic profile, showing an ability to improve indices of glycemic control in men with diabetes. Furthermore, low endogenous testosterone levels have been associated with increased inflammatory markers, and TRT may help decrease the production of inflammatory cytokines, which are implicated in the development of atherosclerosis. These actions suggest a potential anti-atherosclerotic effect, where the hormone may help prevent the buildup of plaque in arteries.
A well-known and expected side effect of testosterone administration is its impact on the blood’s composition, specifically an increase in hematocrit, which is the volume percentage of red blood cells in the blood. This increase, known as polycythemia, can thicken the blood, raising the risk of clotting and venous thromboembolic events. Monitoring hematocrit is an ongoing part of TRT management. Additionally, while TRT can improve vascular function, some testosterone products have been observed to increase blood pressure, leading to a new FDA requirement for specific blood pressure monitoring information on product labels.
Clinical Guidelines for Prescribing to Cardiac Patients
The decision to prescribe TRT to a man with heart disease begins with a thorough screening process to confirm a true deficiency. This requires the patient to present with classic symptoms of hypogonadism and to have low total testosterone levels, typically below 300 nanograms per deciliter, confirmed by two separate morning blood draws. Clinicians must rule out other causes for the symptoms and ensure the patient is not acutely ill, as illness can temporarily suppress testosterone levels.
For patients with established heart conditions, specific cautions govern the initiation of therapy. TRT should be delayed for three to six months following any acute cardiovascular event, such as a myocardial infarction or stroke, to ensure cardiac stability. Therapy should be used with caution or avoided entirely in patients with severe, uncontrolled congestive heart failure, as testosterone can lead to fluid retention and edema, worsening heart failure symptoms.
Ongoing monitoring is mandatory for all patients, especially those with pre-existing CVD. The goal of treatment is to use the lowest effective dose to restore testosterone levels to the mid-normal range, generally between 450 and 600 nanograms per deciliter, while avoiding supraphysiologic (above normal) levels that may increase risks. Monitoring includes:
- Checking the hematocrit level at baseline, then again at three to six months, and annually thereafter, to mitigate the risk of polycythemia.
- Regularly assessing blood pressure and the patient’s cardiac status.
- Counseling the patient to report any symptoms of clotting, such as leg pain or swelling.
- Counseling the patient to report signs of heart rhythm changes, like palpitations.