Cardiovascular safety on TRT

For a decade, the question of whether TRT raises cardiovascular risk has been genuinely unresolved. Observational studies suggested concern. A controversial 2013 cohort study prompted an FDA warning. Competing meta-analyses concluded opposite things. The question was only resolved in 2023 when the TRAVERSE trial, specifically designed to answer it, reported. This article explains what the evidence now says, what the residual concerns are, and how we monitor cardiovascular safety on TRT.

The headline: TRAVERSE showed no increase in MACE

TRAVERSE (Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE) was a 5,200-patient, 5-year, randomised, placebo-controlled trial of TRT in hypogonadal men aged 45 to 80 with pre-existing cardiovascular disease or high risk. Primary endpoint was major adverse cardiovascular events (MACE): cardiovascular death, non-fatal myocardial infarction, non-fatal stroke.

Result: TRT was non-inferior to placebo for MACE. There was no increase in cardiovascular death, no increase in stroke, no increase in MI. This is the largest and highest-quality evidence we have on the question.

This settles the primary concern. Giving TRT to a hypogonadal man does not raise his risk of heart attack, stroke, or cardiovascular death.

The residual concerns TRAVERSE raised

TRAVERSE did identify modest signals for increased risks that matter:

- Increased risk of atrial fibrillation (roughly 30 percent relative risk increase) - Increased risk of pulmonary embolism (roughly 50 percent relative risk increase, absolute rates remained low) - Increased risk of acute kidney injury - No signal for prostate cancer - No signal for all-cause mortality

These secondary signals are small in absolute terms but real. We watch for them particularly in men with baseline atrial fibrillation risk, personal or strong family history of venous thromboembolism, and existing kidney disease.

What this means in practice for us

Absolute CV contraindications to starting TRT. Active unstable cardiovascular disease, recent MI or stroke (within 6 months), severe uncontrolled heart failure (NYHA class IV), severe uncontrolled hypertension (above 180/110 despite medication), active venous thromboembolism, recent pulmonary embolism.

Caution and specialist input. Known coronary disease with reasonable control, recent stented coronary disease, controlled heart failure, atrial fibrillation history, recurrent DVT history.

Proceed with routine monitoring for most men. Controlled cardiovascular risk factors (hypertension managed, diabetes managed), normal baseline ECG, no active symptoms.

Haematocrit and cardiovascular risk

The mechanism most often cited for TRT cardiovascular risk is raised haematocrit causing blood viscosity and thrombotic potential. The evidence here is clearer than for other mechanisms.

Haematocrit rises reliably on TRT by roughly 3 to 5 percentage points over the first 6 to 12 months and then plateaus. Haematocrit above 0.52 is concerning; above 0.54 needs intervention (dose reduction, spreading injection doses, or therapeutic venesection).

Men with untreated sleep apnoea are particularly prone to large haematocrit rises on TRT. Treating the apnoea with CPAP usually controls this. We screen for apnoea at baseline and again if haematocrit rises unexpectedly.

See the dedicated haematocrit article for the detail.

Blood pressure on TRT

Blood pressure does not typically rise on TRT in the absence of fluid retention or supraphysiological dosing. A small percentage of men on supraphysiological doses develop raised blood pressure that resolves on dose reduction.

We monitor blood pressure at every review. A sustained rise of more than 10 mmHg systolic triggers a medication review and dose reconsideration.

Lipids on TRT

Lipid changes on TRT are usually modest and in some cases favourable. Total cholesterol and LDL tend to drop slightly in hypogonadal men receiving TRT. HDL changes are variable; a small minority see HDL fall, particularly on higher doses or orally.

We monitor lipids annually. Adverse lipid trajectory triggers a review but usually does not require stopping TRT.

Atrial fibrillation

TRAVERSE's atrial fibrillation signal is small but real. Men with a history of atrial fibrillation or atrial flutter who start TRT should be aware of a modest increased risk of recurrence. Men with no AF history do not need specific screening beyond routine.

We ask about palpitations, episodic irregular heartbeat, breathlessness on exertion. If AF is suspected, we arrange ECG and Holter monitoring via cardiology referral.

Venous thromboembolism

The PE signal in TRAVERSE is small but consistent with older observational data that TRT may modestly raise VTE risk, particularly in the first few months. Men with a personal history of DVT or PE, men with thrombophilia, or men with recent hospitalisation or surgery need careful assessment before starting TRT.

We do not prescribe TRT to men with active VTE. We proceed with caution in men with remote history of VTE who are no longer anticoagulated. We discuss the specific risk and monitoring plan.

Integration with cardiovascular risk management

Men on TRT benefit from active cardiovascular risk management. QRISK3 assessment, ApoB, Lp(a), CAC scoring where available, blood pressure management, lipid management, lifestyle interventions. Our cardiovascular prevention service integrates with TRT care; most men on TRT have their annual comprehensive review cover both.

When we stop or reduce TRT for CV reasons

Significant rise in haematocrit not controllable by dose adjustment. New diagnosis of unstable coronary disease or heart failure. New diagnosis of atrial fibrillation with recurrent episodes. New VTE event. Sustained significant rise in blood pressure not responsive to medication. Significant lipid deterioration.

In each of these cases, the decision is made with the patient, with cardiology or haematology input where appropriate, and with the alternatives considered (dose change, form switch, adjunct addition, temporary pause).

What we do not do

We do not ignore cardiovascular risk markers. We do not treat TRT as cosmetic where serious CV disease is present. We do not prescribe TRT as a "cardiovascular preventive" (it is not; TRT treats hypogonadism, not cardiovascular disease).

The honest bottom line

TRT is cardiovascularly safe for most hypogonadal men, including those with cardiovascular risk factors. TRAVERSE settled the major concern. Small residual concerns (AF, VTE) are managed with appropriate patient selection and monitoring. Men with active or unstable cardiovascular disease should not start TRT until their cardiovascular situation is stable.

Ready to start?

If this article has made you think an assessment might help, the next step is a short consultation with one of our men's health doctors.

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