Testosterone treatment and risk of venous thromboembolism: population based case-control study

Abstract

Objective To determine the risk of venous thromboembolism associated with use of testosterone treatment in men, focusing particularly on the timing of the risk.Design Population based case-control studySetting 370 general practices in UK primary care with linked hospital discharge diagnoses and in-hospital procedures and information on all cause mortality.Participants 19 215 patients with confirmed venous thromboembolism (comprising deep venous thrombosis and pulmonary embolism) and 909 530 age matched controls from source population including more than 2.22 million men between January 2001 and May 2013.Exposure of interest Three mutually exclusive testosterone exposure groups were identified: current treatment, recent (but not current) treatment, and no treatment in the previous two years. Current treatment was subdivided into duration of more or less than six months.Main outcome measure Rate ratios of venous thromboembolism in association with current testosterone treatment compared with no treatment were estimated using conditional logistic regression and adjusted for comorbidities and all matching factors.Results The adjusted rate ratio of venous thromboembolism was 1.25 (95% confidence interval 0.94 to 1.66) for current versus no testosterone treatment. In the first six months of testosterone treatment, the rate ratio of venous thromboembolism was 1.63 (1.12 to 2.37), corresponding to 10.0 (1.9 to 21.6) additional venous thromboembolisms above the base rate of 15.8 per 10 000 person years. The rate ratio after more than six months’ treatment was 1.00 (0.68 to 1.47), and after treatment cessation it was 0.68 (0.43 to 1.07). Increased rate ratios within the first six months of treatment were observed in all strata: the rate ratio was 1.52 (0.94 to 2.46) for patients with pathological hypogonadism and 1.88 (1.02 to 3.45) for those without it, and 1.41 (0.82 to 2.41) for those with a known risk factor for venous thromboembolism and 1.91 (1.13 to 3.23) for those without one.Conclusions Starting testosterone treatment was associated with an increased risk of venous thromboembolism, which peaked within six months and declined thereafter.

Testosterone Treatment and Cardiovascular and Venous Thromboembolism Risk: What is ‘New’?

“…After the adjustment for confounders, TTh was not associated with an increased risk of VTE (adjusted ratio, 0.90 (0.73 to 1.12)) 54. In contrast to this study, a more recent report reached opposite findings 55. In this study, data were derived from 370 general practitioners in UK primary care, including all men aged 20–89 years registered in the Clinical Practice Research Datalink.…”

Thromboembolism Peaking 3 Months after Starting Testosterone Therapy: Testosterone–Thrombophilia Interactions

“…We and others speculate that VTE events peaking around 3 months,28 with a subsequent sharp decline, may reflect TT-induced depletion of susceptible29 thrombophilic patients from the population, leaving a thrombophilia-winnowed residual group with progressively fewer VTE events over time despite continuation of testosterone supplementation.…”

“…Seventy-six per cent of the thrombotic events occurred in a time frame ranging from <1 month to 8 months after starting TT. Martinez et al 28 recently examined relationships of TT and risk of VTE. Participants included 19,215 patients with confirmed VTE (DVT and PE) and 909,530 age-matched controls from a source population including >2.22 million men 28.…”

“…Martinez et al 28 recently examined relationships of TT and risk of VTE. Participants included 19,215 patients with confirmed VTE (DVT and PE) and 909,530 age-matched controls from a source population including >2.22 million men 28. Rate ratios of VTE in association with current TT were compared with no treatment by conditional logistic regression, adjusted for comorbidities and all matching factors 28.…”

“…Participants included 19,215 patients with confirmed VTE (DVT and PE) and 909,530 age-matched controls from a source population including >2.22 million men 28. Rate ratios of VTE in association with current TT were compared with no treatment by conditional logistic regression, adjusted for comorbidities and all matching factors 28. In the first six months of TT, the rate ratio of VTE was 1.63 (95 per cent CI 1.12 to 2.37) corresponding to 10.0 (1.9–21.6) additional VTE events above the base rate of 15.8/10,000 person-years 28.…”