Testosterone therapy is associated with a short-term increased risk for VTE in men with and without hypogonadism, researchers say.

The findings, published in JAMA Internal Medicine, reinforce the need for caution and regulatory restrictions around the prescribing of testosterone, they wrote.

The case-control crossover study comprised almost 40,000 men with at least one inpatient or two outpatient claims for VTE and data for at least 12 months preceding their VTE event. Men with cancer were excluded.

Among the men without hypogonadism, only 1% of the study group had been prescribed testosterone in the year before their VTE.

However 42.8% of the men with hypogonadism had been prescribed testosterone.

“Testosterone prescriptions in the 1-month (OR, 1.66; 95% CI, 1.34-2.04), 3-month (OR, 2.28; 95%CI, 1.91-2.72), and 6-month (OR, 2.32; 95% CI, 1.97-2.74) case periods were also associated with approximately double the risk of VTE compared with the control periods 6 months earlier after adjusting for confounders,” the study found.

Risk of VTE did not differ with route of administration of testosterone.

The researchers said the study provided novel information about the time frame of exposure to testosterone therapy and risk of VTE.

“Our exploratory analysis found evidence that risk estimates were higher in the 1- to 3-month and less than 1-month case periods compared with the 3- to 6-month case periods.”

“This observation is analogous to patterns seen for oral contraceptives and VTE risk, whereby women are at greatest risk shortly after beginning oral contraceptive use, and provides hypothesis-generating information for future research on testosterone therapy and VTE.”

The study also found the association between testosterone and VTE was stronger in men younger than 65 years compared with older men, although the difference was not statistically significant.

Nevertheless the authors said the finding was of potential public health importance because of recent trends in increased testosterone therapy prescriptions among men younger than 65 years.

“Men younger than 65 years who begin testosterone therapy early to deter common health symptoms potentially associated with aging may be exposing themselves to greater risk of early-onset cardiovascular disease outcomes, especially if there is no clinical indication for starting therapy.”

“These findings complement prior work suggesting that testosterone therapy use is associated with greater risk of stroke and myocardial infarction and suggest that practitioners should be cautious when prescribing testosterone therapy,” they concluded.