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Testosterone Therapy and Risk of Venous Thromboembolism
Study Questions:
What is the associated risk of short-term testosterone therapy and venous thromboembolism (VTE) in men with and without evidence of hypogonadism?
Methods:
Using a case-crossover study design, the authors analyzed data on 39,622 men from the IBM MarketScan Commercial Claims Database and the Medicare Supplemental Database between 2011 and 2017. Patients were identified if they were free of cancer at baseline and with 12 months of continuous enrollment before an index VTE event. The exposure of interest was use of testosterone therapy in the 0-6 months prior to index VTE event as compared to use of testosterone therapy in the 6-12 months prior to index VTE.
Results:
Among the 39,622 men in the study, 3,110 (7.8%) had a diagnosis of hypogonadism. Testosterone therapy use was associated with a higher risk of VTE both in men with (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.97-2.74) and without (OR, 2.02; 95% CI, 1.47-2.77) a diagnosis of hypogonadism. Among the men without a diagnosis of hypogonadism, testosterone therapy was more common in the 6 months immediately before an index VTE event than in the period 6-12 months prior to a VTE event (OR, 2.02; 95% CI, 1.47-2.77). In this group, use of testosterone therapy was associated with a nonsignificantly higher risk of VTE in younger (age <65 years) patients (OR, 2.33; 95% CI, 1.91-4.68) as compared to older (age ≥65 years) patients (OR, 1.41; 95% CI, 0.77-2.56). Among men with a diagnosis of hypogonadism, use of testosterone therapy was more common in the 6 months immediately before an index VTE event than in the 6-12 months prior (OR, 2.33; 95% CI, 1.97-2.74).
Conclusions:
The authors concluded that testosterone therapy is associated with an increased short-term risk for VTE among men with and without hypogonadism.
Perspective:
There is strong evidence linking the use of estrogen therapy with an increased risk of VTE among women. However, the connection between testosterone therapy and VTE risk has not been consistently linked. Due to its association with elevated hematocrit, platelet accumulation, and thromboxane A2 concentrations, it is hypothesized that VTE risk could be elevated after testosterone therapy. This case-crossover study suggests a significant link between testosterone use and short-term (6-month) VTE risk. This risk is similar in men with and without a diagnosis of hypogonadism. This is a particularly important finding given that up to 3% of American men are prescribed this therapy, even without a formal diagnosis of hypogonadism. Clinicians should be cautious about the use of testosterone therapy due to potential complications (e.g., VTE risk), especially for patients without a formal diagnosis of hypogonadism.
Keywords: Blood Platelets, Hematocrit, Hypogonadism, Primary Prevention, Risk, Testosterone, Thromboxane A2, Vascular Diseases, Venous Thromboembolism
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