Attention: Restrictions on use of AUA, AUAER, and UCF content in third party applications, including artificial intelligence technologies, such as large language models and generative AI.
You are prohibited from using or uploading content you accessed through this website into external applications, bots, software, or websites, including those using artificial intelligence technologies and infrastructure, including deep learning, machine learning and large language models and generative AI.

JU INSIGHT: Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy

By: Jesse Ory, MD; Sirpi Nackeeran, BA; Navin C. Balaji, BEng; Joshua M. Hare, MD; Ranjith Ramasamy, MD | Posted on: 01 Jun 2022

Ory J, Nackeeran S, Balaji NC 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. J Urol 2022; 207: 1295.

Study Need and Importance

There is no direct evidence for what constitutes a safe hematocrit in men using testosterone therapy (TT). Guideline-based cutoffs were extrapolated from data from the general population and not in men who were using TT. This is important, as polycythemia in other clinical scenarios has been shown to increase the risk of major adverse cardiovascular events (MACEs) and venous thromboembolism (VTE). Whether or not secondary polycythemia from TT is an independent risk factor for MACE or VTE has never been directly studied.

Figure. Association between TT, MACE/VTE and polycythemia. The levels of evidence of the association or lack thereof are indicated.

“We found that men with polycythemia had a higher risk of MACE and VTE (5.15%) versus men who did not develop polycythemia (3.87%).”

What We Found

From a database of 74 million people, we identified 2 cohorts of men with a low testosterone who received TT and subsequently either developed polycythemia (hematocrit ≥52%, 5,887 patients) or did not develop polycythemia (42,784). After propensity-score matching for multiple risk factors for MACE and VTE, we were able to compare 5,842 men in each group. Our primary outcome was incidence of MACE and VTE in the first year of TT. We found that men with polycythemia had a higher risk of MACE and VTE (5.15%) versus men who did not develop polycythemia (3.87%). We also showed that hypogonadal men on testosterone versus those off testosterone had similar rates of MACE/VTE in the absence of polycythemia (see Figure).

Limitations

The population of men identified was comorbid and largely Caucasian, limiting the generalizability of our results to minorities and healthy men. Additionally, baseline hematocrit was different in the polycythemia group (47.4%) versus the nonpolycythemia group (42.5%).

“Men using testosterone should be aware that they are at a higher risk of MACE and VTE if their hematocrit reaches or exceeds 52% during the first year of therapy.”

Interpretations for Patient Care

Men using testosterone should be aware that they are at a higher risk of MACE and VTE if their hematocrit reaches or exceeds 52% during the first year of therapy. Additionally, in the absence of polycythemia, TT does not appear to increase the risk of MACE and VTE.