If you’re considering testosterone replacement therapy, cardiovascular safety is almost certainly one of your first concerns. For over a decade, headlines have warned that TRT might increase the risk of heart attacks and strokes, leaving many men with genuinely low testosterone reluctant to pursue treatment. Some GPs still cite these concerns when declining referrals.
But the evidence has moved on considerably. The landmark TRAVERSE trial, published in 2023, has fundamentally reshaped our understanding of TRT and heart health. The picture that emerges is far more nuanced, and far more reassuring, than the alarming headlines ever suggested.
This article examines the full evidence on TRT and cardiovascular risk: the historical concerns, the modern trial data, why low testosterone itself is a cardiac risk factor, and what responsible monitoring looks like. If you’re weighing up whether TRT is right for you, this is the cardiovascular information you need.
The Historical Concerns: Where the Fear Started
The association between TRT and cardiovascular danger gained traction in 2013 and 2014, following two widely publicised studies. The first, published in JAMA in November 2013, was a retrospective analysis of veterans receiving TRT. It suggested a 29% increased risk of adverse cardiovascular outcomes. The second, published in PLOS ONE in 2014, reported increased heart attack risk in the first 90 days of TRT use, particularly in older men and those with pre-existing heart disease.
These studies generated enormous media attention. The FDA issued a safety warning, and regulatory agencies in the UK and Europe took note. Many prescribers became cautious, and some stopped offering TRT altogether.
However, both studies had significant methodological problems. They were observational (not randomised controlled trials), relied on administrative databases with incomplete data, and used statistical approaches that were widely criticised by endocrinologists and cardiologists. The JAMA study, in particular, contained acknowledged errors that required subsequent correction. Multiple subsequent analyses of the same data failed to reproduce its findings.
These were not bad studies in isolation, but they were preliminary signals that needed proper investigation. What they were not was definitive proof that TRT harms the heart.
The TRAVERSE Trial: The Evidence That Changed Everything
The question of TRT and heart health was settled, as much as any medical question can be, by the TRAVERSE trial (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men). Published in the New England Journal of Medicine in June 2023, it remains the largest and most rigorous randomised controlled trial of TRT ever conducted.
Study Design
TRAVERSE enrolled 5,246 men aged 45 to 80 who had confirmed hypogonadism (low testosterone) and either pre-existing cardiovascular disease or multiple cardiovascular risk factors. This was a deliberately high-risk population: if TRT was going to cause cardiovascular harm, this is the group where you would expect to see it.
Participants were randomised to receive either testosterone gel (1.62%) or a placebo, with doses adjusted to maintain testosterone levels within the normal physiological range. The study followed these men for a mean of 33 months, with some participants followed for up to five years.
The Key Finding
The primary outcome was major adverse cardiovascular events (MACE): a composite of cardiovascular death, non-fatal heart attack, and non-fatal stroke. The result was clear: TRT did not increase the risk of major adverse cardiovascular events. The event rates were nearly identical in both groups (7.0% in the testosterone group versus 7.3% in the placebo group). The hazard ratio was 0.96, with a confidence interval that comfortably excluded meaningful harm.
This was not a study that merely failed to find harm due to insufficient statistical power. It was specifically designed and powered to detect a cardiovascular safety signal if one existed, in a population selected for elevated cardiovascular risk, and it found none.
What TRAVERSE Did Not Show
It is important to be precise about what the study demonstrated. TRAVERSE showed that physiological-dose TRT does not increase cardiovascular risk. It did not demonstrate that TRT is cardioprotective, nor was it designed to. The study also used testosterone gel at doses calibrated to achieve normal testosterone levels. Its findings do not necessarily extend to supraphysiological doses, injectable testosterone at high doses, or anabolic steroid misuse.
Low Testosterone as a Cardiovascular Risk Factor
Here is the part of the conversation that often gets overlooked: low testosterone is itself an independent risk factor for cardiovascular disease. The fear of TRT has historically overshadowed the risks of leaving hypogonadism untreated.
What the Evidence Shows
Multiple large observational studies and meta-analyses have consistently demonstrated that men with low testosterone have:
- Higher rates of coronary artery disease compared to men with normal testosterone levels
- Increased cardiovascular mortality, with some studies showing a 35-50% higher risk of death from cardiovascular causes
- Higher prevalence of metabolic syndrome, including central obesity, insulin resistance, dyslipidaemia, and hypertension
- Increased arterial stiffness, an early marker of atherosclerotic disease
- Higher rates of type 2 diabetes, itself a major cardiovascular risk factor
A 2010 meta-analysis published in the Journal of Clinical Endocrinology & Metabolism found that low testosterone was associated with a 35% increase in overall mortality and a 25% increase in cardiovascular mortality. A subsequent meta-analysis in 2018 confirmed these findings with even larger datasets.
The Mechanisms
The relationship between low testosterone and cardiovascular risk is mediated through several pathways:
| Mechanism | Effect of Low Testosterone | Cardiovascular Impact |
|---|---|---|
| Visceral adiposity | Increased abdominal fat | Promotes insulin resistance, inflammation, and dyslipidaemia |
| Insulin sensitivity | Reduced glucose uptake | Increases risk of type 2 diabetes and metabolic syndrome |
| Lipid profile | Increased triglycerides, reduced HDL | Promotes atherosclerotic plaque formation |
| Endothelial function | Impaired nitric oxide production | Reduced vasodilation, increased arterial stiffness |
| Inflammatory markers | Elevated CRP and IL-6 | Chronic low-grade inflammation accelerates atherosclerosis |
| Body composition | Reduced lean mass, increased fat mass | Worsens metabolic profile and physical inactivity |
In other words, the question is not only “is TRT safe for the heart?” but also “is leaving low testosterone untreated safe for the heart?” The evidence increasingly suggests that, for men with genuine hypogonadism, untreated low testosterone carries real cardiovascular consequences.
Haematocrit and Polycythaemia: The Risk You Can Manage
If there is one cardiovascular-adjacent risk of TRT that warrants genuine attention, it is polycythaemia: an excessive increase in red blood cells. Testosterone stimulates erythropoiesis (the production of red blood cells in the bone marrow), and in some men, this can push haematocrit levels above safe thresholds.
Why It Matters
Haematocrit is the proportion of your blood volume occupied by red blood cells. Normal male haematocrit ranges from approximately 0.40 to 0.52 (40-52%). When haematocrit rises above 0.54 (54%), blood becomes significantly more viscous. This increased viscosity raises the risk of:
- Deep vein thrombosis (DVT)
- Pulmonary embolism
- Stroke
- Myocardial infarction
This is the most commonly cited cardiovascular concern with TRT, and it is a legitimate one. However, it is entirely manageable with appropriate monitoring.
How We Monitor and Manage It
At Evernu, haematocrit is checked as part of your baseline bloods before commencing TRT and at every subsequent monitoring blood test (typically every 3 to 6 months). Our protocol follows British Society for Sexual Medicine (BSSM) guidelines:
- If haematocrit rises above 0.52, we review the testosterone dose and consider reduction
- If haematocrit rises above 0.54, we reduce the dose or pause treatment
- Therapeutic venesection (blood donation or removal) can be used to lower haematocrit if needed
- In rare cases where haematocrit cannot be controlled, TRT may need to be discontinued
The risk of polycythaemia is higher with injectable testosterone (particularly long-acting esters like testosterone undecanoate) than with transdermal preparations (gels or creams), because injections produce higher peak testosterone levels. This is one reason why the route of administration matters and why treatment should be individualised.
The critical takeaway: polycythaemia becomes dangerous only when it goes unmonitored. This is one of the strongest arguments against obtaining testosterone without proper medical supervision. With regular blood tests, it is a manageable risk, not a reason to avoid treatment.
Blood Pressure and TRT
The relationship between TRT and blood pressure is more nuanced than a simple “it raises blood pressure” or “it lowers blood pressure” summary would suggest.
Some studies have found modest increases in systolic blood pressure with TRT, typically in the range of 2-5 mmHg. Others have found no significant change, or even small reductions, particularly in men who experience significant improvements in body composition (loss of visceral fat, gain of lean mass).
The TRAVERSE trial found a small but statistically significant increase in systolic blood pressure in the testosterone group compared to placebo (approximately 1-2 mmHg). While this is clinically modest, it underscores the importance of monitoring blood pressure during TRT, especially in men with pre-existing hypertension.
Practical Implications
- Blood pressure should be measured at baseline and at each follow-up appointment
- Men with existing hypertension should have their blood pressure well-controlled before starting TRT
- If blood pressure rises significantly during TRT, antihypertensive medication may need adjustment
- Lifestyle measures (regular exercise, sodium reduction, weight management) remain important alongside TRT
Lipid Profile Considerations
TRT has complex effects on blood lipids. The most consistently observed change is a modest reduction in HDL cholesterol (the “good” cholesterol), typically in the range of 5-10%. Some studies also show reductions in total cholesterol and LDL cholesterol, and effects on triglycerides are variable.
In the TRAVERSE trial, the testosterone group had a small reduction in HDL cholesterol compared to placebo, but this did not translate into increased cardiovascular events. The clinical significance of the HDL reduction in the context of overall cardiovascular risk remains debated.
Regular lipid profile monitoring during TRT ensures that any changes are detected early and can be managed with lifestyle modifications or, if necessary, lipid-lowering medication.
Who Should Be Cautious?
While the evidence is broadly reassuring for most men, there are specific groups who require extra caution or for whom TRT may be contraindicated:
- Men with recent cardiovascular events: If you have had a heart attack or stroke within the past 6 months, most guidelines recommend waiting before starting TRT. The TRAVERSE trial excluded men with very recent events.
- Uncontrolled heart failure: Testosterone can cause fluid retention, which may worsen heart failure symptoms. TRT is not absolutely contraindicated in heart failure, but careful assessment is essential.
- Severe untreated sleep apnoea: Obstructive sleep apnoea is both a cardiovascular risk factor in its own right and can be worsened by TRT. Sleep apnoea should be treated (typically with CPAP) before starting testosterone.
- Very high baseline haematocrit: Men who already have elevated haematocrit (above 0.50) are at higher risk of developing polycythaemia on TRT and require especially careful monitoring.
- Uncontrolled hypertension: Blood pressure should be adequately managed before commencing TRT.
None of these represent absolute contraindications in every case. They represent situations where an experienced clinician needs to weigh the benefits against the risks on an individual basis.
The Importance of Monitoring
The common thread running through every cardiovascular consideration of TRT is the same: monitoring makes the difference. The cardiovascular risks associated with TRT, such as they are, are almost entirely risks of unmonitored treatment. With regular blood tests and clinical reviews, they are detectable and manageable.
A comprehensive monitoring protocol for cardiovascular safety during TRT includes:
| Test | Baseline | Follow-up Frequency | Purpose |
|---|---|---|---|
| Full blood count (including haematocrit) | Yes | Every 3-6 months | Detect polycythaemia |
| Lipid profile | Yes | Every 6-12 months | Monitor HDL, LDL, triglycerides |
| Blood pressure | Yes | Every visit | Detect hypertension changes |
| HbA1c / fasting glucose | Yes | Every 6-12 months | Monitor metabolic health |
| Liver function tests | Yes | Every 6-12 months | General health monitoring |
| Testosterone levels | Yes | Every 3-6 months | Ensure physiological dosing |
This is not optional. Regular monitoring is a fundamental part of safe TRT, and any provider who does not include it as standard is not providing adequate care.
What Should You Do?
If you suspect you have low testosterone and are concerned about cardiovascular risk, here is a practical approach:
- Get tested properly. A testosterone blood test will confirm whether your levels are genuinely low. Symptoms alone are not sufficient for diagnosis, and treatment should never be started without confirmed biochemical deficiency.
- Take the ADAM questionnaire. Our online testosterone screening questionnaire can help you identify whether your symptoms are consistent with low testosterone and whether further investigation is warranted.
- Discuss your cardiovascular history. When you consult with our clinicians, be open about any cardiovascular conditions, risk factors, or family history. This allows us to tailor your treatment plan and monitoring schedule appropriately.
- Don’t avoid treatment out of outdated fear. The TRAVERSE trial has provided the highest level of evidence that physiological TRT does not increase cardiovascular risk. If you have symptomatic hypogonadism, avoiding treatment based on fears that the evidence no longer supports may be doing you more harm than good.
- Commit to monitoring. If you start TRT, commit to the monitoring schedule your clinician recommends. This is how cardiovascular safety is maintained in practice.
The Bottom Line
The evidence on TRT and heart health has evolved significantly. The TRAVERSE trial, the most rigorous study ever conducted on this question, found no increased cardiovascular risk with appropriately dosed TRT, even in men at elevated cardiovascular risk. Meanwhile, the evidence that low testosterone itself is a cardiovascular risk factor continues to accumulate.
TRT is not without any cardiovascular considerations. Haematocrit can rise, blood pressure may change modestly, and HDL cholesterol can decrease slightly. But these are monitoring issues, not reasons to withhold treatment from men who need it.
The real cardiovascular risk of TRT is not the therapy itself. It is unmonitored therapy: testosterone obtained without medical oversight, without blood tests, and without clinical follow-up. With proper care, TRT is one of the most evidence-supported and safely monitored treatments available for men with symptomatic low testosterone.
If you’re ready to take the first step, complete our free testosterone screening questionnaire or order a testosterone blood test to find out where you stand. Our clinicians are here to help you make an informed decision based on the best available evidence.
