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.


Elevated hematocrit (Hct) can result in increased risk of major adverse cardiovascular events (MACE) in men receiving testosterone therapy (TTh). However, the impact of the magnitude of the change in Hct from baseline after starting TTh has never been assessed.

Materials and Methods:

To assess whether an increase in Hct after initiating TTh is associated with an increased risk of MACE within 3 and 24 months of initiating TTh, we queried the TriNetX Research network database for men over the age of 18 with Hct values obtained within 6 months before starting TTh, and who had follow-up Hct measurements within 3 and 24 months after beginning TTh from 2010 to 2021. Men with and without a subsequent increase in Hct after initiating TTh were propensity matched. MACE was defined as myocardial infarction, stroke, or death.


After matching, 10,511 men who experienced an any increase in Hct after initiating TTh and an equal number of controls who did have an increase in Hct were included. Compared to controls who did not have an increase in Hct after starting TTh, the men who had an increase in subsequent Hct had a significantly increased risk of MACE compared to men with no change in Hct.


We demonstrate that increases in Hct from baseline are associated with increased risk of MACE, compared to men whose Hct remains stable while receiving TTh.


  • 1. . Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018; 103(5):1715-1744. Crossref, MedlineGoogle Scholar
  • 2. . European Association of Urology guidelines on sexual and reproductive health-2021 update: male sexual dysfunction. Eur Urol. 2021; 80(3):333-357. Crossref, MedlineGoogle Scholar
  • 3. . The relationship between serum total testosterone and free testosterone levels with serum hemoglobin and hematocrit levels: a study in 1221 men. Aging Male. 2016; 19(4):209-214. Crossref, MedlineGoogle Scholar
  • 4. . Effects of testosterone therapy on BMI, blood pressure, and laboratory profile of transgender men: a systematic review. Andrology. 2017; 5:881-888. Crossref, MedlineGoogle Scholar
  • 5. . Testosterone therapy and secondary erythrocytosis. Int J Impot Res. 2022; 34(7):693-697. Crossref, MedlineGoogle Scholar
  • 6. . Erythrocytosis and polycythemia secondary to testosterone replacement therapy in the aging male. Sex Med Rev. 2015; 3(2):101-112. Crossref, MedlineGoogle Scholar
  • 7. . Canadian Urological Association guideline on testosterone deficiency in men: evidence-based Q&A. Can Urol Assoc J. 2021; 15(5):E234-E243. Crossref, MedlineGoogle Scholar
  • 8. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018; 200(2):423-432. LinkGoogle Scholar
  • 9. . 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(6):1295-1301. LinkGoogle Scholar
  • 10. . A U-shaped relationship between haematocrit and mortality in a large prospective cohort study. Int J Epidemiol. 2013; 42(2):601-615. Crossref, MedlineGoogle Scholar
  • 11. . Outcomes of SARS-CoV-2 infection in patients with cystic fibrosis: a multicenter retrospective research network study. Respir Med. 2021; 188:106606. Crossref, MedlineGoogle Scholar
  • 12. Characteristics and outcomes of COVID-19 in patients with HIV: a multicentre research network study. Aids. 2020; 34(13):F3. Crossref, MedlineGoogle Scholar
  • 13. . Outcomes of COVID-19 in solid organ transplant recipients: a propensity-matched analysis of a large research network. Transplantation. 2021; 105(6):1365-1371. Crossref, MedlineGoogle Scholar
  • 14. . Association of testosterone therapy with risk of venous thromboembolism among men with and without hypogonadism. JAMA Intern Med. 2020; 180(2):190-197. Crossref, MedlineGoogle Scholar
  • 15. . Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008; 93(3):914-919. Crossref, MedlineGoogle Scholar
  • 16. . Testosterone therapy, association with age, initiation and mode of therapy with cardiovascular events: a systematic review. Clin Endocrinol (Oxf). 2016; 85(3):436-443. Crossref, MedlineGoogle Scholar
  • 17. . Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews. Lancet Diabetes Endocrinol. 2016; 4(11):943-956. Crossref, MedlineGoogle Scholar
  • 18. . Testosterone lab testing and initiation in the United Kingdom and the United States, 2000 to 2011. J Clin Endocrinol Metab. 2014; 99(3):835-842. Crossref, MedlineGoogle Scholar
  • 19. . Provider and site-level determinants of testosterone prescribing in the Veterans healthcare system. J Clin Endocrinol Metab. 2017; 102(9):3226-3233. Crossref, MedlineGoogle Scholar
  • 20. . Guideline-discordant care among direct-to-consumer testosterone therapy platforms. JAMA Intern Med. 2022; 182(12):1321-1323. Crossref, MedlineGoogle Scholar
  • 21. The effect of route of testosterone on changes in hematocrit: a systematic review and Bayesian network meta-analysis of randomized trials. J Urol. 2022; 207(1):44. LinkGoogle Scholar
  • 22. . Impact of testosterone therapy on hematocrit and polycythemia: evaluation of data from two ongoing open-label randomized single-center clinical trials. J Endocr Soc. 2021; 5(suppl 1):A759-A760. CrossrefGoogle Scholar

Support: None.

Conflict of Interest Disclosures: R.R. is a consultant for Coloplast, Endo, Aytu Biosciences, and Direx; an investigator for Boston Scientific, Endo, Aytu Biosciences, and Direx; and an advisory board member for Endo and Aytu Biosciences. The other authors have nothing to disclose.

Ethics Statement: In lieu of a formal ethics committee, the principles of the Helsinki Declaration were followed.

Author Contributions: All authors listed have contributed sufficiently to the study to be included as authors, and all those who are qualified to be authors are listed. There are no individuals who have contributed to this manuscript or study who are not authors listed. None of the authors has a potential conflict of interest regarding this paper. All authors have agreed to the submission and changes in the manuscript.

Data Availability: Data regarding any of the subjects in the study have not been previously published. Available data will be made available to the editors of the journal for review or query upon request.

Editor's Note: This article is the fifth of 5 published in this issue forwhich Category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 337 and 338.