Testosterone therapy increases the short-term risk of venous thromboembolism (VTE) among men regardless of hypogonadism status, according to a new study.

In a case-crossover study, testosterone therapy was associated with significant 2.3- and 2.0-fold increased odds of VTE in men with and without hypogonadism, respectively, after adjusting for age, Rob F. Walker, MPH, and colleagues reported in JAMA Internal Medicine.

Using the IBM MarketScan Commercial Claims and Encounter Database and the Medicare Supplemental Database, the investigators identified 39,622 men with VTE cases who were free of cancer at baseline and had 12 months of continuous enrollment in an insurance plan before the VTE event.

“To our knowledge, we had the largest number of cases included in a study evaluating testosterone therapy as a potential VTE risk factors,” the investigators wrote.

Of the 3110 men with hypogonadism, 1330 (42.8%) were prescribed testosterone in the 12 months before their VTE event. Of the 36,512 men without hypogonadism, 374 (1.0%) were prescribed testosterone in the 12 months prior to their VTE event.

The investigators defined exposure case periods of 6 months, 3 months, and 1 month before the incident VTE event, with equivalent exposure control periods starting 6 months before the corresponding case period. Each case patient served as his own control. Walker and his collaborators defined case periods based on the time that testosterone therapy is thought to affect pathophysiologic factors known to increase VTE risk.

Among men without hypogonadism, testosterone prescriptions were more common in the 6 months immediately before the VTE event (294 men) than in the control period (177 men). Testosterone use in the 1-, 3, and 6-month case periods was significantly associated with 1.96-, 2.02-, and 2.46-fold increased odds of VTE, respectively, compared with testosterone use in the equivalent control periods in adjusted analyses.

Among men with hypogonadism, testosterone use also was higher in during 6-month case period (1069 men) than in the control period (697 men). Testosterone use in the 1-, 3-, and 6-month case periods were significantly associated with approximately 1.66-, 2.28-, and 2.32-fold increased odds of VTE, respectively, compared with the control periods 6 months earlier after adjusting for confounding variables.

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The study found no significant difference in VTE risk among the various routes of testosterone administration.

“Men experiencing common symptoms that result from natural aging have considered testosterone therapy as a treatment; however, men without hypogonadism should assess cardiovascular disease risk with their physicians before prescription to minimize adverse cardiovascular outcomes,” Walker’s team concluded.