Does TRT Cause Blood Clots? What TRAVERSE, the FDA Label and the Cohort Studies Show About DVT and Pulmonary Embolism

In TRAVERSE, venous blood clots occurred in 1.7% of men on testosterone gel and 1.2% on placebo, and pulmonary embolism in 0.9% vs 0.5%. Here is what that means, what the cohort studies add, and how hematocrit fits in.

Does TRT cause blood clots? The honest answer is that testosterone therapy appears to raise the risk of venous blood clots a little, and the absolute numbers are small. In the TRAVERSE trial, the largest placebo-controlled study of testosterone ever run, venous thromboembolism (VTE) occurred in 1.7% of men on testosterone gel and 1.2% of men on placebo, according to the FDA-approved AndroGel 1.62% label. Pulmonary embolism, the dangerous kind of clot that lodges in the lungs, occurred in 0.9% vs 0.5%.

Those figures were described as numerically higher, not as a proven difference. But they line up with several large observational studies that also found more clots in men using testosterone. This article walks through the trial data, the cohort studies, the meta-analyses that disagree, and what the label now tells doctors and patients to do.

Testosterone therapy is linked to a small increase in venous blood clots, but the evidence falls short of proof that TRT causes them. The best randomized data, from TRAVERSE, showed more deep vein thrombosis (DVT) and pulmonary embolism (PE) in the testosterone group, and the FDA label for AndroGel 1.62% reports those rates directly. Large observational studies agree in direction. Meta-analyses of smaller randomized trials found no statistically significant increase, yet their confidence intervals are wide enough that a meaningful risk cannot be excluded.

Venous thromboembolism is the umbrella term for clots in the veins. A DVT usually forms in the deep veins of the leg. If part of that clot breaks off and travels to the lungs, it becomes a pulmonary embolism. These are different from the arterial clots behind most heart attacks and strokes, which TRAVERSE examined separately and which did not increase on testosterone.

The TRAVERSE trial found a higher incidence of pulmonary embolism in men on testosterone than in men on placebo. TRAVERSE (Lincoff and colleagues, New England Journal of Medicine, 2023) enrolled 5246 men aged 45 to 80 who had heart disease or a high risk of it, symptoms of hypogonadism and two fasting testosterone readings under 300 ng/dL. They used daily 1.62% testosterone gel, adjusted to keep levels between 350 and 750 ng/dL, or a placebo gel. Mean treatment lasted 21.7 months and mean follow-up was 33.0 months.

TRAVERSE was designed to test heart attacks, strokes and cardiovascular death. On that question testosterone was noninferior to placebo: a major cardiac event occurred in 7.0% of the testosterone group and 7.3% of the placebo group (hazard ratio 0.96). The NEJM abstract added that a higher incidence of atrial fibrillation, acute kidney injury and pulmonary embolism was observed in the testosterone group. Our full guide to TRAVERSE and heart attack and stroke risk covers the cardiac results in detail.

The FDA label is the most precise public source for the clot numbers. It states that in TRAVERSE, AndroGel 1.62% was associated with a numerically higher incidence of VTE (1.7% vs 1.2%), which included DVT (0.6% vs 0.5%) and PE (0.9% vs 0.5%). The word numerically matters. The trial was not built to test clots, and the label does not claim a statistically proven difference. Most of the gap came from pulmonary embolism rather than leg clots.

Large observational studies of insurance and health records have found more venous blood clots in men using testosterone. Walker and colleagues (JAMA Internal Medicine, 2020) used a case-crossover design on 39,622 men with a VTE, comparing each man's testosterone use in the 6 months before the clot with his own earlier use. Testosterone use was associated with higher VTE risk in men with hypogonadism (odds ratio 2.32) and in men without a hypogonadism diagnosis (odds ratio 2.02).

Walker's team also looked at age. Among men without hypogonadism, the odds ratio over a 3-month window was 2.99 for men under 65 and 1.68 for older men. That difference was not statistically significant (P = .14), so it suggests rather than proves that younger men without a clear deficiency may carry more short-term risk. The authors concluded that caution should be used when prescribing testosterone.

Bonnet and colleagues (European Journal of Endocrinology, 2025) used the TriNetX network to compare 117,908 hypogonadal men treated with testosterone against matched untreated men. Over 5 years, testosterone was associated with a higher risk of pulmonary embolism or DVT (hazard ratio 1.26) and of atrial fibrillation (hazard ratio 1.27), alongside a slightly lower risk of heart attack (hazard ratio 0.94). Cohort studies like these can show association but cannot rule out that men who get prescribed testosterone differ in other ways.

Meta-analyses of randomized trials have found no statistically significant link between TRT and blood clots because the trials were small and clots are rare. Ayele and colleagues (Thrombosis Research, 2021) pooled 13 randomized trials with 5050 men and found a relative risk of 1.03, with a 95% confidence interval of 0.49 to 2.14. The authors rated the evidence low quality and wrote that a clinically important increased risk cannot be ruled out.

Houghton and colleagues (Thrombosis Research, 2018) combined 6 randomized trials with 2236 men and 5 observational studies with 1,249,640 men. The pooled odds ratio was 1.41 (95% CI 0.96 to 2.07), short of statistical significance, with high heterogeneity (84.4%). Cannarella and colleagues (Asian Journal of Andrology, 2024) restricted their analysis to men with total testosterone under 12 nmol/L. In randomized data the VTE odds ratio was 1.42 with a very wide interval (0.22 to 9.03), and they wrote that DVT risk remains uncertain because so few trials measured it.

Most of these pooled estimates sit above 1.0, which points toward more clots, while their intervals also cross 1.0, which means chance cannot be excluded. TRAVERSE alone enrolled more men than the randomized trials pooled in any of these meta-analyses, which is why its clot data, even as a secondary finding, now shapes the label.

High hematocrit on TRT is linked to more cardiovascular events and blood clots, and the FDA label treats it as a clot risk. Testosterone stimulates red blood cell production, which raises hematocrit, the share of blood volume made up of red cells. The AndroGel 1.62% label states that an increase in red blood cell mass may increase the risk of thromboembolic events, and it tells prescribers to stop therapy if hematocrit becomes elevated until it falls to an acceptable level.

Ory and colleagues (Journal of Urology, 2022) tested this in a database study. They compared 5,842 men on testosterone who developed polycythemia, defined as hematocrit of 52% or higher, with 5,842 matched men on testosterone whose hematocrit stayed normal. In the first year, major cardiovascular events or VTE occurred in 5.15% of the polycythemia group and 3.87% of the normal group (odds ratio 1.35). In the same paper, hypogonadal men on testosterone overall showed no increased risk compared with untreated hypogonadal men. Our guide to hematocrit on TRT explains how dose, delivery method and blood donation affect the number.

The FDA label for AndroGel 1.62% lists venous thromboembolism as a warning, cites the TRAVERSE rates and tells doctors to stop treatment if a clot is suspected. The label's revision history shows the VTE warning updated in 07/2025, a new blood pressure warning added the same month, and the older cardiovascular risk warning removed. In other words, after TRAVERSE the label became less worried about heart attacks and more specific about venous clots and blood pressure.

The label instructs clinicians to evaluate leg pain, swelling, warmth and redness for DVT, and acute shortness of breath for PE. If a venous clot is suspected, treatment with the gel should be discontinued and a workup started. The patient counseling section repeats this in plain terms and adds chest pain to the list of warning signs.

Men with a past clot, a known clotting disorder or rising hematocrit are the groups most worth discussing with a doctor before starting testosterone. That guidance is partly drawn from the studies above and partly from general clot medicine, because no trial has tested testosterone specifically in men with a prior DVT or PE. The Walker data also hint that younger men without documented hypogonadism may see a larger short-term jump, though that comparison was not statistically significant.

• A personal history of DVT or pulmonary embolism. The evidence here is limited, so this needs an individual decision with a clinician.
• A known inherited or acquired clotting disorder, or a family history of unexplained clots.
• Hematocrit that climbs on therapy. In the Ory study, 52% or higher was linked to more events in year one.
• Testosterone use without a confirmed deficiency. Walker found raised odds in men without a hypogonadism diagnosis too.
• The first months of therapy. Both the Walker and Ory analyses focused on short-term windows of 6 months and one year.

For men over 40, the clot data are a reason to start TRT with monitoring rather than a reason to avoid it outright. TRAVERSE showed that testosterone did not raise heart attacks or strokes in a high-risk group, and the venous clot gap was about half a percentage point. Confirming a true deficiency with repeated morning tests, keeping hematocrit in range and knowing the warning signs address most of what the research points to.

• Confirm low testosterone before treating; see our guide to testing testosterone accurately.
• Get a baseline hematocrit, a recheck at 3 to 6 months and annual checks after that.
• Tell your prescriber about any past clot, clotting disorder or long periods of immobility.
• Know the signs: one-sided leg pain or swelling, sudden breathlessness or chest pain.
• Ask about estradiol and hematocrit together; our guide to estradiol on TRT covers how they interact.

This article is for educational purposes only and is not medical advice. It does not diagnose, treat, cure or prevent any disease. Sudden shortness of breath, chest pain, or a painful swollen leg needs urgent medical care, whether or not you use testosterone.

• Lincoff AM et al. Cardiovascular Safety of Testosterone-Replacement Therapy (TRAVERSE). New England Journal of Medicine, 2023. https://doi.org/10.1056/NEJMoa2215025
• AndroGel (testosterone gel) 1.62% prescribing information, sections 5.2, 5.3 and 17.3. DailyMed, US National Library of Medicine, 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4e8d29b-8707-4d47-e053-2a95a90aecee
• Walker RF et al. Association of Testosterone Therapy With Risk of Venous Thromboembolism Among Men With and Without Hypogonadism. JAMA Internal Medicine, 2020. https://doi.org/10.1001/jamainternmed.2019.5135
• Bonnet F et al. Testosterone therapy and the risk of atrial fibrillation, venous thromboembolism and cardiovascular events in cis men with hypogonadism and trans men. European Journal of Endocrinology, 2025. https://doi.org/10.1093/ejendo/lvaf183
• Houghton DE et al. Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis. Thrombosis Research, 2018. https://doi.org/10.1016/j.thromres.2018.10.023
• Ayele HT et al. Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials. Thrombosis Research, 2021. https://doi.org/10.1016/j.thromres.2020.12.029
• Cannarella R et al. Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis. Asian Journal of Andrology, 2024. https://doi.org/10.4103/aja202352
• Ory J et al. Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy. Journal of Urology, 2022. https://doi.org/10.1097/JU.0000000000002437

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