Testosterone Replacement Therapy (TRT) and blood clots

Men often ask a straight question: if I start testosterone replacement therapy, do I raise my risk of a blood clot? The fair answer is measured. When TRT is used to restore testosterone to a normal physiologic range in men with true hypogonadism, the overall risk appears low. A small, mostly early signal has shown up in a few modern studies after treatment begins, and the risk concentrates in men who already lean pro-thrombotic (meaning more likely to form blood clots). That’s the frame to keep in mind.

Why clots are even on the table

Testosterone can raise red blood cell mass. If hematocrit climbs too high, blood gets thicker and flow slows down but this is one piece of the clotting puzzle. Peaks from large, frequent injections push hematocrit more than steady transdermal dosing or longer-interval injections. Aromatization to estradiol at supraphysiologic levels may add a minor push, but that’s a performance enhancement discussion issue, not a replacement-dose (TRT) issue. The bigger multipliers are familiar: recent surgery or long immobility, obesity, smoking, dehydration on travel, active cancer, and inherited or acquired thrombophilia. Stack a few of those with a rising hematocrit / hemoglobin; and you’ve built a risk profile that TRT alone wouldn’t have created.

What the newest studies actually show

A large randomized trial in 2023 followed middle-aged and older hypogonadal men at cardiovascular risk on testosterone gel versus placebo. The primary cardiac outcome was similar between groups, which is reassuring. A safety table showed more pulmonary embolism in the testosterone arm. That doesn’t prove causation, but it keeps venous thromboembolism (blood clots) on the radar, especially in the first months. This is one contrast point between TRT and use of oral contraceptive therapy for birth control. The risk profile seems to be mostly present during early TRT whereas birth control's blood clot risk is long lasting.

Observational work in 2020 used a case-crossover design where each man served as his own control. The risk of a clot was modestly higher shortly after starting therapy and faded with time. That pattern matches what many clinicians see: if a problem is going to appear, it tends to show up near initiation or a rapid dose increase.

When researchers pooled trials and cohorts in 2021, they found no clear overall increase in clots with TRT, but the confidence bounds were wide enough that a small excess couldn’t be ruled out. A 2024 update kept the same theme: randomized trials look neutral; some real-world cohorts suggest a modest deep-vein thrombosis signal. A recent physiological study followed hypogonadal men for six months and did not find a worsening in global coagulation on thrombin-generation testing after restoring testosterone.

Put together, modern data support a small, mostly theoretical risk that’s time-limited and amplified by individual factors. It is not a blanket “no,” and it is certainly not a reason to ignore symptoms.

Who needs extra caution

Men with prior unprovoked DVT or PE, a strong family history of early clots, or a known thrombophilia (ex. Factor V Leiden, prothrombin G20210A, antithrombin deficiency, protein C or S deficiency, antiphospholipid antibodies etc.) deserve a slower, tighter plan or perhaps should avoid TRT altogether. So do men with severe obesity, active cancer, recent major surgery or trauma, prolonged immobility, smoking, untreated sleep apnea, or baseline hematocrit that already runs high. TRT isn't an absolute contraindication but it can be a relative contraindication.

Bottom line

For men with clear hypogonadism, testosterone replacement has a small, mostly time-limited clotting risk that concentrates in the first months and in those with stacked risk factors. Keep dosing physiologic, avoid peaks, control hematocrit, fix the modifiable risks, and teach the warning signs. That approach matches the best modern evidence and keeps therapy safe for the men who truly need it.

Our Kitchener and Waterloo TRT Clinic serves patients in Kitchener, Waterloo, Guelph and Cambridge, Ontario.

References (recent)

1. Lincoff AM, et al. Cardiovascular safety of testosterone-replacement therapy: TRAVERSE randomized trial. New England Journal of Medicine. 2023.

2. Walker RF, et al. Short-term risk of venous thromboembolism after initiation of testosterone therapy: case-crossover analysis. JAMA Internal Medicine. 2020.

3. Ayele HT, et al. Testosterone therapy and venous thromboembolism: systematic review and meta-analysis. 2021.

4. Cannarella R, Calogero AE, et al. Testosterone therapy and VTE risk: updated review of randomized and observational evidence. 2024.

5. Lanzi V, et al. Effects of testosterone replacement on global coagulation (thrombin-generation) in hypogonadal men. Journal of Clinical Endocrinology & Metabolism. 2024.