Testosterone Replacement Therapy (TRT) is a medical treatment prescribed to men diagnosed with hypogonadism, a condition characterized by abnormally low testosterone levels accompanied by specific symptoms. This therapy is distinct from using testosterone to treat age-related declines, which is generally not recommended. The relationship between TRT and cardiovascular health has been a subject of extensive research and debate. Early observational studies raised concerns about the hormone’s safety in heart patients, requiring careful consideration before treatment begins.
The Current Medical Stance on Cardiovascular Safety
The safety profile of TRT has undergone a substantial evolution, moving from initial caution to a more nuanced understanding supported by large-scale clinical data. Historically, several large observational studies suggested a possible increased risk of heart attack and stroke, leading the U.S. Food and Drug Administration (FDA) to issue warnings in 2015. These warnings required manufacturers to include information about a possible increased risk of major adverse cardiovascular events (MACE) on product labels.
Recent, robust evidence from a major, randomized, placebo-controlled trial involving over 5,200 men has provided significant clarity. This study included men with confirmed low testosterone who either had established cardiovascular disease or were at high risk. The trial found that TRT was “noninferior” to a placebo, meaning it did not increase the risk of MACE (cardiovascular death, non-fatal heart attack, or non-fatal stroke).
Following the release of these results, the FDA removed the language regarding increased risk of heart attack and stroke from the boxed warning in early 2025. The current medical consensus is that TRT does not appear to increase the overall risk of major cardiovascular events when used to treat confirmed hypogonadism. Regulatory guidance still emphasizes that the drug should only be prescribed for men with clinically diagnosed low testosterone, not for age-related “Low T.”
Physiological Effects on Heart and Blood Vessels
Testosterone exerts biological effects that directly influence the cardiovascular system. One of the most consistent effects is the stimulation of red blood cell production, known as erythrocytosis. This increase in red blood cells elevates the hematocrit level, which increases the blood’s viscosity. Blood that is too thick may flow less efficiently and carry an increased risk of blood clots.
The hormone also impacts blood pressure and vascular function. Testosterone can influence the renin-angiotensin-aldosterone system, a hormonal network that regulates blood pressure and fluid balance. It can promote sodium retention, which may lead to a modest increase in blood pressure. This potential for small blood pressure increases has led to new regulatory warnings for testosterone products.
The influence of testosterone on cholesterol is generally considered beneficial for cardiovascular health, especially in men with hypogonadism. Restoring testosterone levels to a normal range can improve the lipid profile. This often includes a decrease in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, while sometimes increasing the protective high-density lipoprotein (HDL) cholesterol. These systemic metabolic improvements may contribute to the overall cardiovascular safety observed in recent large trials.
Essential Cardiovascular Screening and Monitoring
For heart patients considering TRT, a screening process is required to ensure safety and manage potential side effects. Before starting therapy, a physician must conduct a comprehensive cardiovascular risk assessment and confirm the diagnosis of hypogonadism with at least two morning blood tests showing low testosterone levels. Baseline blood work must also include a lipid panel and a hematocrit measurement to establish a reference point for future monitoring.
Any patient with existing heart disease or multiple risk factors should consult a cardiologist before initiating TRT. This consultation helps ensure that the patient’s cardiac condition is stable enough to begin hormone therapy. TRT is often avoided in men who have had a recent acute cardiac event (within the last three to six months) or those with uncontrolled or severe heart failure due to the risk of fluid retention.
Once therapy begins, monitoring is essential to mitigate risks. Regular checks of testosterone levels are necessary to ensure they remain within the target physiological range and avoid excessively high levels. The primary safety measure is the frequent monitoring of hematocrit, typically checked at the three- and six-month marks and then annually, to detect erythrocytosis. If the hematocrit rises above the acceptable threshold (typically 50% to 54%), the therapy may need to be temporarily stopped, the dose adjusted, or blood donation (therapeutic phlebotomy) may be required to reduce blood viscosity.