Polycythemia during testosterone therapy linked to CV events, VTE in men: Study

USA: Development of polycythemia in men on testosterone therapy (TT) increased the risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) in the first year of therapy, states an article published in the Journal of Urology.

An unsafe hematocrit threshold for men receiving TT has never been tested. The association between testosterone therapy (TT) and major adverse cardiovascular events (MACE) or venous thromboembolic events (VTE) is a puzzle. Understanding the risk of these adverse events is paramount to safe prescribing and counseling. Jesse Ory, University of Miami, USA, and colleagues investigated whether the development of secondary polycythemia vera during testosterone therapy (TT) is associated with an increased risk of MACEs and VTEs

Testosterone replacement therapy (TT) is ideal for men with testosterone levels below 300 ng/dL or having symptoms of low testosterone. Undergoing TT can help to restore normal testosterone levels and improve libido, cognition, mood, bone density, muscle mass, and red blood cell production in men. Secondary polycythemia is one of the most common adverse events associated with TT and has been shown to cause thrombosis in men with idiopathic erythrocytosis. Multiple professional organizations have established guidelines on safe prescribing of TT and include an upper safe limit for hematocrit(48% to 55%) during therapy.

Investigators used a multi-institutional database of 74 million patients and identified 2 cohorts of men with low testosterone who received TT and subsequently either developed polycythemia (5,887) or did not (4,2784). Polycythemia was defined as hematocrit ≥52%. As a secondary objective, investigators identified 2 cohorts of hypogonadal men without polycythemia, who either did (26,880) or did not (27,430) receive TT. The primary outcome was the incidence of MACE and VTE in the first year after starting TT.

Key findings of the study,

• Men with polycythemia had a higher risk of MACE/VTE than men who had normal hematocrit while on TT (p <0.001).

• Among men with hypogonadism, those who received TT had similar rates of MACEs/VTEs compared with those who did not receive TT.

Based on the study findings, the authors conclude that in men on TT, developing polycythemia is an independent risk factor for MACE and VTE in the first year of therapy. Men using TT 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, especially men with cardiovascular comorbidities.

In future studies, hematocrit should be included as an independent variable while assessing the safety of TT and hematocrit-based cutoffs should be incorporated into the outcomes of future RCTs investigating MACE/VTE and TT, the authors wrote.

Reference:

Ory J, Nackeeran S, Balaji NC, Hare JM, Ramasamy AR. 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 Jun;207(6):1295-1301. doi: 10.1097/JU.0000000000002437. Epub 2022 Jan 20. PMID: 35050717.