Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2022 Jun;207(6):1295-1301.
doi: 10.1097/JU.0000000000002437. Epub 2022 Jan 20.

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

Jesse Ory  1   2 , Sirpi Nackeeran  3 , Navin C Balaji  3 , Joshua M Hare  4 , And Ranjith Ramasamy  1
Affiliations
Multicenter Study

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

Jesse Ory et al. J Urol. 2022 Jun.

Abstract

Purpose: An unsafe hematocrit threshold for men receiving testosterone therapy (TT) has never been tested. This study seeks to determine whether secondary polycythemia among men receiving TT confers an increased risk of major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE).

Materials and methods: Using a multi-institutional database of 74 million patients, we identified 2 cohorts of men with low testosterone (total testosterone <350 ng/dl) 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, we identified 2 cohorts of hypogonadal men without polycythemia, who either did (26,880) or did not (27,430) receive TT. Our primary outcome was the incidence of MACE and VTE in the first year after starting TT. We conducted a Kaplan-Meier survival analysis to assess differences in MACE and VTE survival time, and measured associations following propensity score matching.

Results: A total of 5,842 men who received TT and developed polycythemia were matched and compared to 5,842 men who did not develop polycythemia. Men with polycythemia had a higher risk of MACE/VTE (number of outcomes: 301, 5.15%) than men who had normal hematocrit (226, 3.87%) while on TT (OR 1.35, 95% CI 1.13-1.61, p <0.001). In hypogonadal men who received testosterone, no increased risk of MACE and VTE was identified as compared to hypogonadal men naïve to TT.

Conclusions: Developing polycythemia while on TT is an independent risk factor for MACE and VTE in the first year of therapy. Future research on the safety of TT should include hematocrit as an independent variable.

Keywords: adverse effects; hypogonadism; polycythemia; testosterone; thromboembolism.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: RR: consultant and grant recipient for Acerus, Boston Scientific, Endo Pharmaceuticals and Coloplast; grant recipient from Empower Pharmacy and Olympus; consultant for Nestle Health; advisory board of Hims, Inc.; Recipient of NIH funding (1R01DK130991-01). JMH: consultant, shareholder and board member for Longeveron, Vestion and Heart Genomics; grant recipient from NHLBI.

Figures

Figure.
Figure.
Kaplan-Meier curves displaying the probability of MACE/VTE in the main (A) and secondary (B) comparison arms. A, men on testosterone who developed secondary polycythemia (hematocrit >52%, blue line) versus men with a normal hematocrit (hematocrit <52%, orange line). B, hypogonadal men who did (orange line) and did not (blue line) receive testosterone. Men who developed hematocrit over 52% were excluded in this analysis.
See this image and copyright information in PMC

Comment in

References

    1. Corona G, Rastrelli G, Di Pasquale G, et al. : Testosterone and cardiovascular risk: meta-analysis of interventional studies. J Sex Med 2018; 15: 820. - PubMed
    1. Walker RF, Zakai NA, MacLehose RF, et al. : Association of testosterone therapy with risk of venous thromboembolism among men with and without hypogonadism. JAMA Intern Med 2020; 180: 190. - PMC - PubMed
    1. Maggi M, Wu FCW, Jones TH, et al. : Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME). Int J Clin Pract 2016; 70: 843. - PubMed
    1. Zhang X, Huang K, Saad F, et al. : Testosterone therapy reduces cardiovascular risk among hypogonadal men: a prospective cohort study in Germany. Androg Clin Res Ther 2021; 2: 64.
    1. Bhasin S, Brito JP, Cunningham GR, et al. : Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2018; 103: 1715. - PubMed

Publication types