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Original Investigation
November 11, 2019

Association of Testosterone Therapy With Risk of Venous Thromboembolism Among Men With and Without Hypogonadism

Author Affiliations
  • 1Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis
  • 2Department of Medicine, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington
  • 3Department of Pathology and Laboratory Medicine, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington
  • 4Department of Biostatistics, Epidemiology, and Environmental Health Sciences, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro
  • 5Department of Pharmaceutical Care and Health Systems, College of Pharmacy, University of Minnesota, Minneapolis
  • 6Department of Epidemiology, Rollins Emory University School of Public Health, Atlanta, Georgia
JAMA Intern Med. 2020;180(2):190-197. doi:10.1001/jamainternmed.2019.5135
Key Points

Question  Is clinical prescription of testosterone therapy associated with short-term risk of venous thromboembolism in men with and without hypogonadism?

Findings  In this case-crossover study comparing 6-month testosterone use for 39 622 men who had a venous thromboembolism with testosterone use 6 to 12 months before the venous thromboembolism, use of testosterone therapy in the 6-month case period was associated with an increased risk of venous thromboembolism among men with and without hypogonadism.

Meaning  The findings suggest that testosterone therapy is associated with increased short-term risk of venous thromboembolism among all men prescribed the therapy.


Importance  Testosterone therapy is increasingly prescribed in patients without a diagnosis of hypogonadism. This therapy may be associated with increased risk of venous thromboembolism (VTE) through several mechanisms, including elevated hematocrit levels, which increase blood viscosity.

Objective  To assess whether short-term testosterone therapy exposure is associated with increased short-term risk of VTE in men with and without evidence of hypogonadism.

Design, Setting, and Participants  This case-crossover study analyzed data on 39 622 men from the IBM MarketScan Commercial Claims and Encounter Database and the Medicare Supplemental Database from January 1, 2011, to December 31, 2017, with 12 months of follow-up. Men with VTE cases who were free of cancer at baseline and had 12 months of continuous enrollment before the VTE event were identified by International Classification of Diseases codes. Men in the case period were matched with themselves in the control period. Case periods of 6 months, 3 months, and 1 month before the VTE events were defined, with equivalent control periods (6 months, 3 months, and 1 month) in the 6 months before the case period.

Exposures  National drug codes were used to identify billed testosterone therapy prescriptions in the case period (0-6 months before the VTE) and the control period (6-12 months before the VTE).

Main Outcomes and Measures  The main outcome in this case-only experiment was first VTE event stratified by the presence or absence of hypogonadism.

Results  A total of 39 622 men (mean [SD] age, 57.4 [14.2] years) were enrolled in the study, and 3110 men (7.8%) had evidence of hypogonadism. In age-adjusted models, testosterone therapy use in all case periods was associated with a higher risk of VTE in men with (odds ratio [OR], 2.32; 95% CI, 1.97-2.74) and without (OR, 2.02; 95% CI, 1.47-2.77) hypogonadism. Among men without hypogonadism, the point estimate for testosterone therapy and VTE risk in the 3-month case period was higher for men younger than 65 years (OR, 2.99; 95% CI, 1.91-4.68) than for older men (OR, 1.68; 95% CI, 0.90-3.14), although this interaction was not statistically significant (P = .14).

Conclusions and Relevance  Testosterone therapy was associated with an increase in short-term risk for VTE among men with and without hypogonadism, with some evidence that the association was more pronounced among younger men. These findings suggest that caution should be used when prescribing testosterone therapy.

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