What’s The Real Risk Of Blood Clot And Stroke With Testosterone Use?

The other day an ER doctor told me that “you shouldn’t use testosterone replacement because it increases your risk for blood clot and stroke.”  He told me this in context of a patient on testosterone replacement therapy (TRT) who recently had a blood clot.

So, in order to ensure that we’re not doing more harm, I took a really deep dive into blood clot risk and the use of testosterone replacement.

The risk of stroke associated with testosterone replacement therapy (TRT) has been a topic of considerable research, for many years, yet the evidence remains inconclusive based on available scholarly articles. Studies present a mixed picture, with some suggesting an increased risk, others finding no significant association, and a few even indicating potential protective effects. I’ve summarized the key findings from the research sources as of March, 2025.

Several observational studies have explored this relationship. A systematic review published in PubMed examined TRT safety in men with respect to stroke risk. Among seven cohort studies of hypogonadal (low testosterone )men, one reported a significant decrease in ischemic stroke risk (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.52-0.80), and another found a similar reduction (HR 0.64; 95% CI 0.43-0.96) in men achieving normalized testosterone levels. However, these findings were tempered by limitations such as immortal time bias and residual confounding, which could skew results. The remaining studies did not provide clear measures of association, leaving the relationship uncertain.

Randomized controlled trials (RCTs) offer additional insight but are limited by small sample sizes and low event rates. In eight RCTs reviewed in the same PubMed article, stroke events were rare (fewer than five per group), preventing definitive conclusions. A notable RCT, the TRAVERSE trial, published in The New England Journal of Medicine in 2023, enrolled over 5,000 men aged 45-80 with low testosterone and high cardiovascular risk. It found no significant increase in stroke or other major cardiovascular events with TRT compared to placebo over a three-year follow-up, though it noted higher rates of pulmonary embolism and atrial fibrillation in the TRT group.

Conversely, some studies suggest an elevated risk. A cohort study from The American Journal of Medicine analyzed 15,401 men with age-related hypogonadism and found a 21% increased risk of cardiovascular events, including ischemic stroke, during the first two years of TRT use (corresponding to an additional 128 events). This risk appeared transient, declining after two years, possibly due to a “depletion of susceptibles” effect. Similarly, a review in Frontiers in Neurology highlighted case reports and observational data linking testosterone supplementation to stroke in young adults, potentially via mechanisms like erythrocytosis and hypercoagulability, though it emphasized the lack of conclusive evidence.

Other research points to potential benefits or neutrality. A 10-year study presented at the European Association of Urology congress found that men with low testosterone on TRT had no strokes, compared to 59 strokes among untreated men, suggesting a protective effect. However, this was not a peer-reviewed publication, and selection bias could influence results. A meta-analysis in The Lancet also found no short- to medium-term increase in stroke risk with TRT in hypogonadal men, though it stressed the need for long-term data.

These differences in findings may stem from differences in study design, population [e.g., hypogonadal vs. eugonadal (normal testosterone) men], TRT dosage, administration route (e.g., transdermal vs. intramuscular), and follow-up duration. For instance, lower doses of transdermal estradiol (?50 ?g/day) showed no altered stroke risk in some studies, unlike higher-dose oral therapies. Age and baseline health also matter—absolute risk is low in younger men (e.g., two additional strokes per 10,000 person-years in those under 60) but rises in older populations.

In summary, the current research articles do not provide a definitive answer on TRT’s stroke risk. The evidence suggests it neither consistently increases nor decreases risk across all contexts, with outcomes varying by individual factors and study limitations. Large, methodologically robust studies are still needed to clarify this relationship. Men considering TRT should weigh these uncertainties with their healthcare providers, especially if they have any cardiovascular risk factors.