Testosterone therapy is primarily indicated for the management of clinical hypogonadism. After a sharp increase in prescriptions for this treatment from 2001 to 2013-attributed to testosterone therapy being prescribed to men who didn't have hypogonadism, particularly those 18 to 45 years of age-the Food and Drug Administration issued a warning in 2014 about the increased risks of heart attack and stroke associated with this therapy. Although the number of prescriptions has since decreased, evidence suggests that testosterone therapy is still being prescribed to men who do not have hypogonadism. Using a case-crossover design, researchers investigated whether exposure to testosterone therapy is associated with an increased risk of incident venous thromboembolism in men stratified by clinical hypogonadism status.

Data on 39,622 men who were cancer-free at baseline and had at least 12 months of follow-up prior to having venous thromboembolism were included in the analysis. Each man served as his own control. Exposure case periods of six months, three months, and one month before the venous thromboembolism event and equivalent control periods were defined. Of the men enrolled in the study, 3,110 had a diagnosis of hypogonadism.

Men prescribed testosterone had approximately twice the risk of venous thromboembolism within the one-, three-, and six-month case periods compared with the equivalent control periods. The association was stronger among men younger than age 65, but these differences were not statistically significant. Associations were similar whether testosterone was administered transdermally or intramuscularly.

Men who do not have hypogonadism should discuss with their clinicians the cardiovascular risks of testosterone therapy, the authors advise.