TRT and Cardiovascular Health: TRAVERSE Trial, Blood Pressure & Hematocrit

Does TRT increase cardiovascular risk?

At replacement doses with proper monitoring, TRT does not increase the risk of major adverse cardiovascular events (MACE). This was definitively established by the TRAVERSE trial, published in the New England Journal of Medicine in June 2023. Prior to TRAVERSE, the cardiovascular question hung over TRT due to conflicting observational data and a controversial 2010 TOM trial that was stopped early for safety concerns in a small, frail elderly population.

The FDA mandated the TRAVERSE trial in 2015 after adding a cardiovascular warning to testosterone product labels based on limited and inconsistent evidence. The resulting study was the gold standard of clinical trials: randomized, double-blind, placebo-controlled, and adequately powered with over 5,000 men. Its conclusion: testosterone therapy is cardiovascularly non-inferior to placebo.

This does not mean TRT has zero cardiovascular impact. It raises hematocrit (increasing blood viscosity), can modestly increase blood pressure, and affects lipid profiles. These changes require monitoring — but they do not translate to increased rates of heart attacks, strokes, or cardiovascular death at replacement doses.

What did the TRAVERSE trial find?

The TRAVERSE trial (Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men) enrolled 5,246 men aged 45-80 with hypogonadism (testosterone below 300 ng/dL) and either pre-existing cardiovascular disease or high cardiovascular risk. Participants were randomized to receive either 1.62% testosterone gel (adjusted to maintain levels of 350-750 ng/dL) or matching placebo for a mean duration of 33 months.

Primary endpoint

The primary composite endpoint was first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (3-point MACE). Results: MACE occurred in 7.0% of the testosterone group versus 7.3% of the placebo group (hazard ratio 0.96, 95% CI 0.78-1.17). The upper bound of the confidence interval (1.17) fell below the pre-specified non-inferiority margin of 1.5, confirming cardiovascular safety.

Key secondary findings

*These secondary endpoints should be interpreted cautiously as the study was not powered for individual secondary outcomes. However, the signals for pulmonary embolism and atrial fibrillation warrant ongoing research and monitoring.

How does TRT affect hematocrit?

Elevated hematocrit (erythrocytosis) is the most common clinically significant cardiovascular-related side effect of TRT, occurring in 20-40% of patients. Testosterone stimulates erythropoiesis (red blood cell production) through multiple mechanisms: it increases erythropoietin (EPO) production, stimulates bone marrow directly, and suppresses hepcidin (which increases iron availability for red blood cell synthesis).

Hematocrit measures the percentage of blood volume occupied by red blood cells. Normal range for adult men is 38.3-48.6%. On TRT, hematocrit typically rises 2-5 percentage points, and in some men can exceed 54% — the threshold at which most guidelines recommend intervention. Elevated hematocrit increases blood viscosity, which theoretically increases the risk of thrombotic events (blood clots, stroke, heart attack), though the TRAVERSE trial did not find increased MACE despite higher hematocrit in the testosterone group.

Management of elevated hematocrit

• Dose reduction: The first intervention. Lowering your testosterone dose directly reduces the erythropoietic stimulus. Even a modest reduction (e.g., 180 mg to 140 mg/week) can bring hematocrit down 2-3 points.
• Therapeutic phlebotomy: Removing a pint of blood (500 mL) reduces hematocrit by approximately 3 percentage points. This can be done through blood donation (if you meet eligibility criteria) or a therapeutic phlebotomy order from your physician.
• Increase injection frequency: More frequent, smaller doses may produce less erythropoietic stimulation than large weekly peaks, though evidence for this specific effect is limited.
• Hydration: Dehydration artificially elevates hematocrit. Ensure adequate hydration before blood draws and in daily life. Hematocrit drawn after a night of poor hydration can read 2-3 points higher than true baseline.
• Switch to topical: Some evidence suggests that topical testosterone produces less hematocrit elevation than injectable formulations, possibly due to more stable serum levels.

Iron depletion concern

Repeated phlebotomy can deplete iron stores. Men who need frequent blood draws (every 2-3 months) should monitor ferritin levels. Symptoms of iron deficiency — fatigue, weakness, brain fog, restless legs — can mimic low testosterone symptoms, creating a frustrating diagnostic overlap. If ferritin drops below 30 ng/mL, iron supplementation may be needed, though this must be balanced against the hematocrit-raising effect of more available iron.

Does TRT raise blood pressure?

TRT can raise blood pressure modestly in some men, typically by 3-5 mmHg systolic. The mechanisms include fluid retention (mediated by both testosterone and estrogen effects on renal sodium handling), increased blood volume from elevated hematocrit, and increased vascular stiffness. The TRAVERSE trial found no significant difference in hypertension incidence between groups, suggesting the effect is clinically modest at replacement doses.

For men with well-controlled or borderline hypertension, the increase may push readings above target. For normotensive men, the change is usually within normal variation. The concern is greatest during the first 3 months of TRT, when fluid retention peaks and hematocrit is rising.

Blood pressure management on TRT

• Monitor blood pressure at home weekly for the first 3 months, then monthly once stable
• Reduce sodium intake to under 2,300 mg/day
• Regular aerobic exercise (150+ minutes/week) is one of the most effective antihypertensive interventions
• If water retention is contributing, address estrogen levels and consider injection frequency changes
• If blood pressure remains elevated (>140/90 or above your personal target), discuss antihypertensive medication with your physician — do not simply accept elevated readings because you are on TRT

How does TRT affect cholesterol and lipids?

TRT consistently reduces HDL cholesterol by approximately 5-10%, an effect observed across multiple studies including TRAVERSE. The mechanism involves testosterone's upregulation of hepatic lipase, which accelerates HDL catabolism. Whether this HDL reduction translates to increased cardiovascular risk is debated — HDL-raising drugs (like niacin and CETP inhibitors) have repeatedly failed to improve cardiovascular outcomes in clinical trials, challenging the assumption that any HDL reduction is harmful.

LDL cholesterol and triglycerides show variable responses to TRT. Some studies report modest LDL reductions; others show no change. Triglycerides typically remain stable. The net effect on atherogenic lipid burden appears neutral to slightly favorable in most men.

A fasting lipid panel should be checked at baseline, 6 months after starting TRT, and annually thereafter. Men on statin therapy should continue their statin on TRT — testosterone is not a substitute for lipid-lowering medication in men with established dyslipidemia.

Does TRT increase the risk of blood clots?

The relationship between TRT and venous thromboembolism (VTE) — deep vein thrombosis (DVT) and pulmonary embolism (PE) — has been debated for years. The TRAVERSE trial found a small but statistically significant increase in pulmonary embolism (0.9% vs 0.5%, p=0.04) in the testosterone group. This signal requires careful interpretation: it was a secondary endpoint in a study not powered for this outcome, and the absolute risk increase was small.

The FDA added a warning about VTE risk to testosterone product labels in 2014 based on post-marketing reports. However, the mechanism is unclear. Elevated hematocrit increases blood viscosity, which could promote clot formation. Some researchers have hypothesized that testosterone may directly affect coagulation factors, but the evidence is inconsistent.

Practical risk assessment: the absolute risk of VTE on TRT is low, but men with pre-existing clotting disorders (Factor V Leiden, prothrombin gene mutation), a history of VTE, recent surgery, or prolonged immobility should discuss additional precautions with their physician. Maintaining hematocrit below 54% reduces one of the modifiable risk factors.

What cardiovascular monitoring do you need on TRT?

Cardiovascular monitoring on TRT is straightforward but non-negotiable. The goal is to catch hematocrit elevation, blood pressure changes, and lipid shifts early — before they produce symptoms or complications. Most guidelines recommend the following schedule.

Home blood pressure monitoring is recommended for all men on TRT. An automated cuff used consistently (same arm, same time of day, seated for 5 minutes) provides much more actionable data than occasional clinic readings. Track your readings in a log or app and bring the data to your appointments.

Who should be cautious about TRT and cardiovascular risk?

While the TRAVERSE trial demonstrated overall cardiovascular safety, certain populations merit closer monitoring or additional discussion with their physician before starting or continuing TRT.

• History of VTE or clotting disorders: The small PE signal in TRAVERSE warrants caution. These men should have a thorough discussion of risk-benefit with a hematologist.
• Uncontrolled hypertension: TRT can worsen blood pressure. Get hypertension under control before starting TRT, and monitor closely during the first 3 months.
• Heart failure (NYHA Class III-IV): Fluid retention from TRT can exacerbate heart failure. The Endocrine Society lists severe heart failure as a relative contraindication.
• Baseline hematocrit above 50%: Starting TRT with already-elevated hematocrit increases the likelihood of exceeding 54%. Investigate the cause of baseline elevation before starting.
• Recent cardiovascular event (<6 months): While TRAVERSE enrolled high-risk men, starting TRT immediately after an MI or stroke adds variables during a critical recovery period. Most clinicians recommend waiting 3-6 months.
• Untreated sleep apnea: Severe OSA is an independent cardiovascular risk factor. Treat the apnea before adding TRT. See our sleep apnea guide for screening recommendations.

Return to the TRT side effects overview for the full picture of how cardiovascular monitoring fits into your overall TRT management plan. If fluid retention is contributing to blood pressure changes, review our water retention guide.