Men on testosterone therapy who experience polycythemia are at increased risk for major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) in the first year of therapy, a new study finds.

Using real-world data from the US TriNetX database, investigators identified 48,671 men with a total testosterone level of less than 350 ng/dL who received testosterone therapy. They propensity-score matched 5887 men who later developed polycythemia, defined as a hematocrit of 52% or more, with 5887 men who did not.

Men with secondary polycythemia had a higher rate of a composite endpoint of MACE/VTE in the first year of testosterone therapy compared with men who had a normal hematocrit: 5.15% vs 3.87%, a team led by Ranjith Ramasamy, MD, of the University of Miami in Florida, reported in The Journal of Urology. Polycythemia while on testosterone therapy significantly increased the odds of MACE/VTE by 35%. In secondary analyses, men with polycythemia had 1.8- and 1.5-fold increased odds of acute myocardial infarction and VTE (including deep vein thrombosis and pulmonary embolism), respectively.

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Testosterone therapy itself did not appear to increase MACE/VTE. In a separate analysis of more than 50,000 patients with hypogonadism and no polycythemia, men on testosterone therapy had no significantly increased risks for the composite outcome compared with untreated men, the investigators reported.

Professional organizations have established guidelines on safe prescribing of testosterone therapy and include an upper safe limit for hematocrit. In the US, the threshold for testosterone therapy cessation is a hematocrit of 50% to 54%.

“Men using testosterone therapy should be aware that they are at a higher risk for MACE/VTE if their hematocrit reaches or exceeds 52% during the first year of therapy,” Dr Ramasamy’s team warned. “This is especially relevant in men with cardiovascular comorbidities.”

The investigators could not analyze hematocrit as a continuous variable, which is a study limitation.

“Hematocrit-based cutoffs should be incorporated into the outcomes of future RCTs investigating MACE/VTE and [testosterone therapy],” the study authors wrote.

More than half of men in the current study had hypertension and/or dyslipidemia, a third were obese, and nearly a quarter had diabetes. Use of cardiovascular medications was common.

Disclosure: This research was partially supported by Acerus Pharmaceuticals. Please see the original reference for a full list of disclosures.


Ory J, Nackeeran S, Balaji NC, Hare JM., Ramasamy R. Secondary polycythemia in men receiving testosterone therapy increases risk for major adverse cardiovascular events and venous thromboembolism in the first year of therapy. J Urol. Published January 20, 2022. doi:10.1097/JU.0000000000002437