title: Sex difference in risk of second but not of first venous thrombosis: paradox explained.
abstract: BACKGROUND
  The risk of recurrent venous thrombosis is 2-fold higher in men than in women. In contrast, no such sex difference in the risk of first venous thrombosis has been reported. We hypothesized that, for a first event, a risk difference between the sexes is masked by female exposure to reproductive factors (oral contraception, pregnancy/puerperium, and postmenopausal hormone therapy).
  
  
  RESULTS
  From the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study, a population-based case-control study on risk factors for venous thrombosis, 2915 patients with a first venous thrombosis and their partners as control subjects were included. Odds ratios and 95% confidence intervals for first venous thrombosis were assessed in men compared with women without reproductive risk factors by use of conditional logistic regression. Analyses were stratified in 10-year age categories to account for the variation in exposure to reproductive risk factors over different age groups and adjusted for body mass index and smoking. Overall, men had a 2.1-fold (95% confidence interval, 1.9-2.4) increased risk of first venous thrombosis compared with women without reproductive risk factors. Similar results were found when 10-year age categories were viewed separately. Adjustment for body mass index and smoking and exclusion of cancer patients did not materially affect the results.
  
  
  CONCLUSIONS
  When female reproductive risk factors are taken into account, the risk of a first venous thrombosis is twice as high in men as in women. These findings are in line with previous studies on recurrent venous thrombosis and may have implications for future treatment and prevention strategies.
authors.affiliation: Department of Clinical Epidemiology (R.E.J.R., W.M.L., F.R.R., S.C.C., S.l.C.), Einthoven Laboratory for Experimental Vascular Medicine (W.M.L., F.R.R., S.C.C.), Thrombosis and Hemostasis Research Center (F.R.R.), and Department of Medical Statistics and Bioinformatics (S.l.C.), Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rachel E J
authors.initials: RE
authors.lastname: Roach
authors.forename: Willem M
authors.initials: WM
authors.lastname: Lijfering
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Cannegieter
authors.forename: Saskia
authors.initials: S
authors.lastname: le Cessie
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D012008:Recurrence; D012307:Risk Factors; D012727:Sex Characteristics; D017678:Sex Distribution; D020246:Venous Thrombosis / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D003276:Contraceptives, Oral
keywords: epidemiology; hormones; risk factors; sex; venous thrombosis