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Clin Pharmacol Ther. 2011 Jan;89(1):60-4. doi: 10.1038/clpt.2010.241. Epub 2010 Nov 24.

Effect of NFE2L2 genetic polymorphism on the association between oral estrogen therapy and the risk of venous thromboembolism in postmenopausal women.

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Laboratoire de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Hôpital Bicêtre, AP-HP, Univ Paris-Sud, Le Kremlin Bicêtre, France.


Oral, but not transdermal, estrogen therapy increases the risk of venous thromboembolism (VTE) in women who are past menopause. Data from the Estrogen and Thromboembolism Risk (ESTHER) study were used to investigate the effects of the genetic polymorphism of NFE2L2 rs6721961, which may impair Nrf2-dependent hepatic conjugation of estrogen metabolites. As compared with nonusers, the odds ratio (OR) for VTE in current users of oral estrogens was 2.5 (95% confidence interval (CI): 1.3-4.8) in patients with wild-type NFE2L2 and 17.9 (95% CI: 3.7-85.7) in those with the polymorphism (interaction, P = 0.01).

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