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In a recently published paper by Renoux and colleagues [1], the risk of venous thromboembolism (VTE) is evaluated for a number of different hormone replacement therapies (HRT) for postmenopausal women. The analysis was made in the United Kingdom’s General Practice Research database using a nested case–control approach. The cohort of 955,582 postmenopausal women aged 50–79 years included 23,505 cases of VTE (2.46%). The analysis highlighted use of non-oral estrogen and tibolone for which 365 (transdermal) and 148 (tibolone) cases of VTE were present.


The increased risk of VTE for users of oral estrogens and oral estrogen–progestogen preparations (2006 cases; adjusted rate ratio (RR) 1.52; 95% confidence interval (CI) 1.44–1.61) was confirmed. This risk with oral formulations was particularly elevated during the first year of use and disappeared 4 months after discontinuation. A stepwise increase in risk was observed with increasing dosages of the estrogen component. There was no increased risk of VTE for transdermal preparations with estrogens or estrogen–progestogen combinations (RR 1.00; 95% CI 0.89–1.12)) and tibolone (RR 0.92; 95% CI 0.77–1.10).


  • Cornelis Kluft
    Centre for Human Drug Research, Leiden, The Netherlands


  1. Renoux C, Dellaniello S, Suissa S. Hormone replacement therapy and the risk of venous thromboembolism: population-based study. J Thromb Haemost 2010 Mar 4. Epub ahead of print.
  2. Canonico M, Oger E, Plu-Bureau G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007;115:840-5.
  3. Straczek C, Oger E, Yon de Jonage-Canonico MB, et al. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration. Circulation 2005;112:3495-500.
  4. Archer DF, Hendrix S, Gallagher JC, et al. Endometrial effects of tibolone. J Clin Endocrinol Metab 2007;92:911-18
  5. Cummings SR, Ettinger B, Delmas PD, et al. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359:697-708.
  6. Kenemans P, Bundred NJ, Foidart JM, et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol 2009;10:135-46.
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