TRT-Induced Erythrocytosis and Blood Clot Risk: What Studies Show
It is a well understood fact that testosterone replacement therapy (TRT) can increase muscle mass, bone density, and blood count. We love the strong muscles and bones, but we are no longer hunting saber tooth tigers or doing battle to protect our tribe. Blood loss is largely a concern of the past, and the extra blood production induced by TRT is sometimes seen as a problem. The concern can vary from mild nuisance to hysteria form ill-informed doctors. Let’s did into the data and really assess the risk of this phenomenon, called TRT associated erythrocytosis.
Several studies have investigated whether erythrocytosis caused by testosterone replacement therapy (TRT) increases the risk of blood clots (venous thromboembolism, VTE). The majority of large-scale and systematic studies have not found a direct causal link between TRT-induced erythrocytosis and increased risk of blood clots in otherwise healthy men.
Key Terms and Understanding
TRT induces an increase in red blood cell production. The increase in the percent of your blood that is red blood cells is called the hematocrit (HCT). An increase in HCT with no increase in platelets or white blood cells is labeled correctly as erythrocytosis
An increased HCT associated with TRT should not be labeled as polycythemia, which more correctly defines a condition in which RBC, WBC, and Platelets are increased. Polycythemia is associated with many risk factors.
While clotting risk is theoretically increased with increased viscosity, the slight increases in HCT seen with TRT have never been associated causally with blood clotting.
Platelets are primarily involved in clotting events, along with other clotting factors, none of which are increased above normal physiological levels with TRT. Thus, there is no scientific reason to expect a clinically significant increase in clotting.
Erythrocytosis as been linked to mild increases in blood pressure. It also makes you feel sluggish.
Best practice should seek to normalize the hematocrit with dose reduction, optimal control of testosterone byproducts like DHT and estrogen, and adequate hydration.
Phlebotomy (blood donations) is used as needed, preferably by routine donations (every 8-12 weeks) to blood banks.
Erythrocytosis is not grounds to discontinue TRT and does not present eminent risk. Care should be taken to avoid misinformation which may be anxiety inducing and inappropriate.
Key Studies Showing No Increased Risk
Baillargeon et al., 2015 (Large Comparative Analysis)
This study analyzed over 30,000 men and found no association between testosterone therapy and an increased risk of blood clots or deep vein thrombosis (DVT). The findings were supported by a comprehensive analysis of 71,407 men, which also found no increase in the likelihood of blood clots in men on TRT compared to controls.
Meta-Analysis of Testosterone Trials
An individual participant dataset meta-analysis comprising 3,431 participants reported no increase in thrombotic events among men receiving testosterone therapy.
American Urological Association (AUA) Guidelines
The AUA guideline states: "Patients should be informed that there is no definitive evidence linking testosterone therapy to a higher incidence of VTE" (AUA, 2018).
Cancer Patient Study (Nehra et al., 2012)
In a cohort of cancer patients, who are at higher baseline risk for blood clots, testosterone therapy did not increase the risk of thrombotic events.
BMJ Observational Studies
Research comparing men on TRT with those not on TRT found no association between testosterone treatment and increased risk of blood clots in men without preexisting blood conditions. Most clotting events were confined to patients with previously undiagnosed thrombophilia.
Additional Context from Reviews and Guidelines
Frontiers in Endocrinology (2025)
Recent reviews emphasize that, while TRT can lead to erythrocytosis, the evidence linking this to increased thrombotic risk is weak—particularly in men without other underlying risk factors.
Endocrinology Clinical Practice Guidelines
These guidelines recommend regular monitoring of hematocrit and adjusting testosterone therapy if levels rise. However, they also acknowledge that a direct causal link to thrombotic events remains unproven.
Conclusion
The current body of evidence, including large cohort studies, meta-analyses, and clinical guidelines, does not support a direct causal relationship between TRT-induced erythrocytosis and increased risk of blood clots in otherwise healthy men. Most concerns are theoretical or based on extrapolation from other conditions. Ongoing monitoring of hematocrit is recommended, but the available studies do not show that erythrocytosis from TRT alone causes blood clots.
References
Cervi, A., & Balitsky, A. K. (2017). Testosterone use causing erythrocytosis. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 189(41), E1286–E1288. https://doi.org/10.1503/cmaj.170683
Ohlander, S. J., Varghese, B., & Pastuszak, A. W. (2018). Erythrocytosis Following Testosterone Therapy. Sexual medicine reviews, 6(1), 77–85. https://doi.org/10.1016/j.sxmr.2017.04.001
Bond, P., Verdegaal, T., & Smit, D. L. (2024). Testosterone therapy-induced erythrocytosis: can phlebotomy be justified?. Endocrine Connections, 13(10), e240283. Retrieved Apr 21, 2025, from https://doi.org/10.1530/EC-24-0283
Ory, J., Nackeeran, S., Balaji, N. C., Hare, J. M., & Ramasamy, and R. (2022). 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, 207(6), 1295–1301. https://doi.org/10.1097/JU.0000000000002437 (Original work published June 1, 2022)
Neidhart, A., von Wyl, V., Käslin, B., Henzen, C., & Fischli, S. (2025). Prevalence and predictive factors of testosterone-induced erythrocytosis: A retrospective single center study. Frontiers in Endocrinology, 15. https://doi.org/10.3389/fendo.2024.1496906
Sharma, R., Oni, O. A., Chen, G., Sharma, M., Dawn, B., Sharma, R., Parashara, D., Savin, V. J., Barua, R. S., & Gupta, K. (2016). Association Between Testosterone Replacement Therapy and the Incidence of DVT and Pulmonary Embolism: A Retrospective Cohort Study of the Veterans Administration Database. Chest, 150(3), 563–571. https://doi.org/10.1016/j.chest.2016.05.007
Glueck CJ, Goldenberg N, Wang P. Testosterone Therapy, Thrombophilia, Venous Thromboembolism, and Thrombotic Events. J Clin Med. 2018 Dec 21;8(1):11. doi: 10.3390/jcm8010011. PMID: 30577621; PMCID: PMC6352146.
Baillargeon, J., Urban, R. J., Morgentaler, A., Baillargeon, G., Sharma, G., & Kuo, Y.-F. (2015). Risk of venous thromboembolism in men receiving testosterone therapy. Mayo Clinic Proceedings, 90(8), 1038–1045. https://doi.org/10.1016/j.mayocp.2015.05.012
Martinez, C., Suissa, S., Rietbrock, S., Katholing, A., Freedman, B., Cohen, A. T., et al. (2016). Testosterone treatment and risk of venous thromboembolism: Population based case-control study. BMJ, 355, i5968. https://doi.org/10.1136/bmj.i5968
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