title: 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.
  
  
  METHODS
  Population based case-control study SETTING:  370 general practices in UK primary care with linked hospital discharge diagnoses and in-hospital procedures and information on all cause mortality.
  
  
  METHODS
  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.
  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.
  
  
  METHODS
  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.
authors.affiliation: Institute for Epidemiology, Statistics and Informatics GmbH, 60388 Frankfurt, Germany carlos.martinez@pharmaepi.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Martinez
authors.affiliation: Centre For Clinical Epidemiology, Lady Davis Research Institute - Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2, Canada.
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
authors.affiliation: Institute for Epidemiology, Statistics and Informatics GmbH, 60388 Frankfurt, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rietbrock
authors.affiliation: Institute for Epidemiology, Statistics and Informatics GmbH, 60388 Frankfurt, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Katholing
authors.affiliation: ANZAC Research Institute, University of Sydney, Concord Hospital, Concord NSW 2139, Australia.|Heart Research Institute, Charles Perkins Centre, University of Sydney, NSW 2006 Australia.|Concord Hospital Dept of Cardiology, Sydney Medical School, University of Sydney, Sidney NSW 2006, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Freedman
authors.affiliation: Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Cohen
authors.affiliation: ANZAC Research Institute, University of Sydney, Concord Hospital, Concord NSW 2139, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000009:adverse effects*; D016022:Case-Control Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012306:Risk; D013739:Testosterone / Q000009:adverse effects*; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D000728:Androgens; D013739:Testosterone