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Recently, Canonico and colleagues published an analysis from the Women’s Health Initiative (WHI) hormone therapy (HT) clinical trial (both estrogen and estrogen + progestin) of venous thromboembolism (VTE) risk and markers of reproductive life related to lifetime endogenous estrogen exposure [1]. These markers included ages at menarche and menopause, number of term pregnancies (parity), bilateral oophorectomy, or time since menopause. Interactions of HT with these characteristics on VTE risk were also evaluated. Postmenopausal women without a history of VTE at baseline ([i]n[/i] = 27,035) were included in the analysis; the mean follow-up was 6.2 years.


There was no interaction between the individual markers and treatment assignment on the risk of a first VTE event found in the analysis. A pooled analysis of first VTE event by individual markers also did not find significant associations. However, pooled analyses restricted to first non-procedure-related VTE event found a significant interaction ([i]p[/i] < 0.01) for age at menopause (a U-shaped relationship). Relative to women having their menopause in their forties, those with early menopause (age < 40 years) or late menopause (age > 55 years) were at significantly greater risk for VTE. Analyses for deep vein thrombosis but not for pulmonary embolism and age at menopause yielded similar results.


  • James H. Pickar
    Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, USA


  1. Canonico M, Plu-Bureau G, OSullivan MJ, et al. Age at menopause, reproductive history, and venous thromboembolism risk among postmenopausal women: the Womens Health Initiative hormone therapy clinical trials. Menopause 2013;21. Epub ahead of print
  2. Grady D, Wenger NK, Herrington D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. Ann Intern Med 2000;132:689-96.
  3. Simon T, De Jonage-Canonico MBY, Oger E, et al. Indicators of lifetime endogenous estrogen exposure and risk of venous thromboembolism. J Thromb Haemostasis 2006;4:71-6.
  4. Lutsey PL, Virnig BA, Durham SB, et al. Correlates and consequences of venous thromboembolism: the Iowa Womens Health Study. Am J Public Health 2010;100:1506-13.
  5. Ohira T, Folsom, AR, Cushman M, et al. Reproductive history, hormone replacement, and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology. Br J Haematol 2010;149:606-12.
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