What the largest, most rigorous trial found about heart attack and stroke risk
The most definitive evidence comes from the TRAVERSE trial, a large, randomized, double-blind, placebo-controlled study published in the New England Journal of Medicine in 2023. It enrolled 5,246 men aged 45-80 who had hypogonadism (low testosterone) and either existing heart disease or a high risk for it. Over an average of 33 months of follow-up, major adverse cardiac events (a composite of death from cardiovascular causes, nonfatal heart attack, or nonfatal stroke) occurred in 7.0% of the testosterone group and 7.3% of the placebo group — a statistically non-significant difference (hazard ratio 0.96) [1]. This means TRT was proven to be non-inferior to placebo, i.e., it did not increase the risk of these major events.
This trial was specifically designed to settle the cardiovascular safety question, and its results are considered the strongest evidence available. The Androgen Society, in a 2024 position paper reviewing all the data, concluded that it has now been 'conclusively determined that TTh is not associated with increased risks of heart attack, stroke, or CV death' [5]. In February 2025, the FDA updated testosterone product labels to remove the boxed warning for major cardiovascular events, replacing it with a warning about blood pressure increases [7].
Why some older studies suggested a risk, and why they were misleading
In 2013-2014, two observational studies reported an increased risk of cardiovascular events in men using TRT, which led to widespread media coverage and an FDA warning in 2015 [5]. These studies were retrospective, meaning they looked back at medical records, and they could not fully account for differences between men who chose to take TRT and those who did not. For example, men with low testosterone often have more underlying health problems like obesity, diabetes, and high blood pressure — all of which independently raise cardiovascular risk. The TRAVERSE trial, by randomly assigning treatment, eliminated this 'confounding' and showed that the apparent risk in the older studies was likely due to the underlying health of the men, not the testosterone itself.
Several of the newer studies in this collection support that conclusion. A 2025 study of men with Klinefelter syndrome (a genetic cause of hypogonadism) found that TRT was associated with lower all-cause mortality (hazard ratio 0.56) and no increase in major cardiovascular events compared to untreated men [2]. Similarly, a 2025 study of men with secondary hypogonadism due to pituitary tumors found no increased risk of MACE with TRT, and untreated hypogonadism was actually linked to higher mortality [4]. A 2025 study in men with heart failure and malnutrition even found that TRT reduced the risk of death (HR 0.56) and acute heart failure (HR 0.62) [3]. These findings consistently point in the same direction: when underlying health is accounted for, TRT does not appear to cause harm.
The remaining cautions: specific risks that still need monitoring
While TRT appears safe regarding major events like heart attack and stroke, the TRAVERSE trial did find a higher incidence of three specific conditions in the testosterone group: atrial fibrillation (an irregular heart rhythm), acute kidney injury, and pulmonary embolism (a blood clot in the lung) [1]. A 2026 review confirmed these signals and noted that the risk of venous thromboembolism (blood clots) may be highest in the first 3-6 months after starting TRT [7]. These are not common events, but they are serious enough that doctors should monitor for them, especially in men with existing risk factors.
The evidence also suggests that the effect of TRT may depend on a man's prior cardiovascular history. A 2024 study of men with type 2 diabetes found that TRT reduced the risk of heart attack in those without prior cardiovascular disease (risk ratio 0.765), but increased the risk of both heart attack and stroke in those with a history of cardiovascular disease (risk ratio 1.164 for heart attack) [6]. This highlights the importance of personalized risk assessment: TRT is not a one-size-fits-all treatment, and men with established heart disease may need more careful evaluation and monitoring. Overall, the current picture is that TRT is safe for most men, but it requires a thoughtful discussion with a healthcare provider about individual risks and benefits.
About These Sources
This answer is built on 7 peer-reviewed studies — published from 2023 to 2026, 6 from 2024 or later, 5 in Q1 journals, collectively cited 373 times — selected as the most relevant from 13 studies that passed quality screening, drawn from 70 papers retrieved from a database of over 500 million.
Sources used in this answer
Cardiovascular Safety of Testosterone-Replacement Therapy
The TRAVERSE trial, a large randomized controlled trial in 5,246 men at high cardiovascular risk, found TRT was non-inferior to placebo for MACE (7.0% vs 7.3%), but noted higher rates of atrial fibrillation, acute kidney injury, and pulmonary embolism.
Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort study
In a Danish registry study of men with Klinefelter syndrome, TRT was associated with lower all-cause mortality (HR 0.56) and no increased risk of MACE compared to untreated men.
Testosterone therapy in patients with heart failure and protein-calorie malnutrition: Insights from a propensity-matched cohort study.
In a propensity-matched study of men with heart failure and malnutrition, TRT reduced the risk of all-cause mortality (HR 0.56), acute heart failure (HR 0.62), and MACE (HR 0.77).
Secondary Hypogonadism and Effects of Testosterone Replacement Therapy on Cardiovascular Events
In men with secondary hypogonadism due to pituitary tumors, TRT did not increase MACE risk, and untreated hypogonadism was associated with increased mortality.
Androgen Society Position Paper on Cardiovascular Risk With Testosterone Therapy
The Androgen Society position paper concludes that TTh is not associated with increased risks of heart attack, stroke, or cardiovascular death, based on the TRAVERSE trial and multiple meta-analyses.
12340 Cardiovascular Risks With Testosterone Replacement Therapy In Patients With Type 2 Diabetes Mellitus
In men with type 2 diabetes, TRT reduced heart attack risk in those without prior CVD (RR 0.765) but increased heart attack and stroke risk in those with prior CVD (RR 1.164).
Testosterone replacement therapy and non‑major adverse cardiovascular events safety signals: Atrial fibrillation, acute kidney injury, and pulmonary embolism.
A review of non-MACE safety signals confirms that TRT is associated with increased risks of atrial fibrillation, acute kidney injury, and pulmonary embolism, and notes the FDA removed the boxed warning for MACE in 2025.