TRT and heart health: What the latest meta-analyses (2024/25) show

The question of whether testosterone replacement therapy (TRT) increases cardiovascular risk has plagued patients and physicians for over a decade. While the TRAVERSE study (2023) already gave the all-clear, four new meta-analyses have been published since then, which significantly strengthen the data situation. We summarize the most important findings — and explain what they mean for your treatment.

Why cardiovascular safety matters

The debate around TRT and heart health dates back to 2010, when a small trial (the TOM trial) was halted prematurely due to cardiovascular events in older, frail men receiving testosterone. Two observational studies published in 2013 and 2014 further fueled concerns. These publications triggered FDA warnings and years of uncertainty — despite critical methodological flaws in the original studies (including data corrections, small sample sizes, and conflicting results).

The landmark TRAVERSE trial (NEJM, 2023) was the first large-scale, placebo-controlled RCT designed specifically to evaluate cardiovascular safety of TRT. With over 5,000 men aged 45–80 who had pre-existing cardiovascular disease or elevated cardiovascular risk, participants were followed for a median of 33 months. The trial demonstrated no increased risk of major adverse cardiovascular events (MACE), including heart attack, stroke, and cardiovascular death [5]. The four meta-analyses published since then consolidate and extend this finding across even larger patient populations.

The four meta-analyses at a glance

1. Braga et al. (2025) — Long-term safety

The most recent meta-analysis examined long-term cardiovascular safety in middle-aged and older men. The evaluation of randomized controlled trials (RCTs) concluded that TRT is not associated with an increased cardiac risk, even over longer treatment periods [1]. This is particularly important because earlier concerns focused on cumulative effects that might only emerge after years of treatment. By pooling long-term follow-up data from multiple RCTs, Braga and colleagues provide the strongest evidence yet that prolonged TRT does not harm the cardiovascular system.

2. Corona et al. (2024) — Systematic evaluation

An Italian research group led by Giovanni Corona evaluated 106 studies with a total of 15,436 participants (8,126 TRT, 7,310 placebo). The result [2]:

• No increased risk of major cardiovascular events (heart attack, stroke, cardiac death)
• No increased risk of atrial fibrillation (despite concerns from individual studies)
• Conclusion of the authors: «Available data confirms that TRT is safe and it is not related to an increased CV risk.»

This is currently the largest and most comprehensive meta-analysis on TRT cardiovascular safety.

3. Jaiswal et al. (2024) — 30 randomized trials

This meta-analysis included 30 RCTs with 11,502 patients and analyzed several outcomes separately [3]:

No single analysis showed an increased risk with TRT. The trend toward lower cardiovascular mortality with TRT (OR 0.87) is consistent with observational data suggesting potential cardiovascular benefits of testosterone normalization.

4. Cannarella et al. (2024) — Thromboembolism

Specifically on the question of whether TRT increases the risk of blood clots (thrombosis, pulmonary embolism), a Sicilian team led by Cannarella evaluated data from over 310,000 patients across 24 studies [4]:

• No increased risk of arterial thrombosis (OR 1.27, p = 0.64)
• No increased risk of stroke (OR 1.34, p = 0.83)
• No increased risk of heart attack (OR 0.51, p = 0.39)
• No increased risk of venous thromboembolism (OR 1.42, p = 0.71)

The observational studies even showed a significant reduction in the risk of thrombosis and mortality with TRT. The authors concluded that TRT in men with total testosterone below 12 nmol/L appears safe regarding arterial and venous cardiovascular endpoints. However, the risk of deep vein thrombosis specifically warrants further investigation due to limited RCT data in this area.

Limitations to keep in mind

Despite the reassuring data, some limitations deserve mention:

1. Study populations: Most trials enrolled men with moderate testosterone deficiency. It is unclear whether results apply equally to men with borderline levels.
2. Follow-up duration: Even the TRAVERSE trial followed patients for a median of under 3 years. Effects that emerge only after 5–10 years cannot yet be confirmed or excluded.
3. Dose and formulation: Meta-analyses pool data from various testosterone preparations (gels, injections, patches) and dosing regimens. Safety may differ between supraphysiological dosing and guideline-conforming TRT.
4. Exclusion criteria: High-risk patients (recent stroke, unstable angina, severe heart failure) were excluded from most trials, so safety in these populations remains uncertain.

Who should exercise extra caution?

While the overall evidence is reassuring, certain patient groups warrant closer cardiovascular monitoring during TRT:

• Men over 65: Although the TRAVERSE trial included older men and found no increased risk, the absolute cardiovascular event rate is naturally higher in older populations, making close monitoring imperative.
• Men with pre-existing heart conditions: Patients with a history of myocardial infarction, coronary artery disease, or heart failure should undergo TRT only after thorough risk-benefit assessment with their cardiologist.
• Men with polycythemia risk: TRT increases red blood cell production. An elevated hematocrit above 54% raises the risk of thromboembolic events. Regular blood count monitoring identifies this complication early, before it becomes dangerous.
• Men with untreated sleep apnea: Obstructive sleep apnea may worsen with TRT in some patients, and sleep apnea itself is an independent cardiovascular risk factor.

These precautions are not contraindications to TRT — they call for individualized treatment decisions and more frequent monitoring intervals.

What does this mean for patients?

The data for 2024/25 is clearer than ever before:

TRT for proven testosterone deficiency, under medical supervision and with regular blood checks, is cardiovascularly safe. Four independent research groups arrive at the same conclusion based on over 15,000 study participants.

This doesn't mean that TRT is risk-free — regular checks of hematocrit, PSA, liver function tests and blood pressure remain essential. But the long-feared serious cardiovascular complications cannot be confirmed by current evidence.

What we do with it at Swiss TRT

These findings flow directly into our treatment protocol:

1. Close monitoring — Full blood count, lipid profile and cardiovascular markers every 3 months for the first 12 months
2. Individual dosing — Target range within the physiological normal range, no supraphysiological doses
3. Risk stratification — Particularly careful consideration and monitoring of pre-existing cardiovascular diseases
4. Transparent information — Patients are informed about the current study situation, not about outdated fears

FAQ

Does testosterone replacement therapy cause heart attacks? According to four major meta-analyses published in 2024–2025—covering over 15,000 participants—there is no evidence that TRT increases the risk of heart attack. The largest study (Corona et al., 106 studies) explicitly concluded that TRT is cardiovascularly safe.

Is TRT safe for older men with heart disease? The TRAVERSE trial (2023) specifically enrolled men aged 45–80 with pre-existing cardiovascular risk factors and found no increase in major adverse cardiovascular events. However, men with unstable heart conditions were excluded, so decisions should be made individually with your doctor.

Do I still need cardiovascular monitoring during TRT? Yes. Even though the data is reassuring, regular monitoring of hematocrit, blood pressure, and lipid profile is essential during TRT—both as a safety precaution and to optimize your treatment outcomes. Guidelines recommend checks every three months during the first year and every six months thereafter. Talk to your doctor about establishing an individualized monitoring plan that is tailored to your specific cardiovascular risk profile and medical history.

How is TRT different from anabolic steroid abuse regarding heart risk? TRT aims to restore testosterone to normal physiological levels (typically 15–25 nmol/L), whereas anabolic steroid abuse involves supraphysiological doses 5–100 times higher. The cardiovascular safety data applies only to medically supervised, guideline-conforming TRT, not to steroid misuse.

Further Reading

• Is TRT safe? What science really says
• TRT side effects: What you really need to know
• At what testosterone level does therapy make sense?