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Inhibitors and activation markers of the haemostatic system during hormone therapy: A comparative study of oral estradiol (2 mg)/ dydrogesterone and estradiol (2 mg)/ trimegestone

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Author: Norris, L.A. · Brosnan, J. · Bonnar, J. · Conard, J. · Kluft, C. · Hellgren, M.
Institution: TNO Kwaliteit van Leven
Source:Thrombosis and Haemostasis, 2, 100, 253-260
Identifier: 240938
doi: doi:10.1160/TH07-12-0746
Keywords: Health · Haemostasis · Hormones · Venous thrombosis · Activated protein C · Antiplasmin · Antithrombin · Blood clotting factor 5 Leiden · Dydrogesterone plus estradiol · Estradiol plus trimegestone · Estrogen derivative · Plasmin · Protein S · Prothrombin · Adult · Aged · Clinical trial · Controlled clinical trial · Controlled study · Double blind procedure · Drug effect · Drug inhibition · Female · Fibrinolysis · Gene mutation · Hormonal therapy · Human · Medical assessment · Multicenter study · Multiple cycle treatment · Postmenopause · Protein blood level · Protein function · Randomized controlled trial · Administration, Oral · Estrogen Replacement Therapy · Factor V · Hemostasis · Humans · Middle Aged · Progestins · Promegestone · Protein C · Protein S · Risk Factors · Venous Thrombosis


Epidemiological studies have shown that hormone therapy (HT) increases the risk of venous thromboembolism in post menopausal women. The mechanism of this increased risk is unknown; however, activation of the haemostatic system is known to contribute to the pathogenesis of venous thromboembolism. In post-menopausal women the estrogen /progestogen composition of the HT can influence the level of haemostatic activation. It was the objective of this study to compare changes in inhibitors and activation markers of the haemostatic system in healthy post-menopausal women taking estradiol (2 mg) combined with dydrogesterone or a new progestin, trimegestone. A multicentre study of 186 women randomised to six months therapy with either estradiol (2 mg) +trimegestone (0.5 mg) or estradiol (2 mg) +dydrogesterone (10 mg) was performed. Antithrombin and protein S activity was decreased and activated protein C (APC) resistance, D-dimer and prothrombin fragment 1.2, were increased in both groups on treatment. Protein C activity was decreased and plasmin-antiplasmin complex was increased in the trimegestone group only. The increase in plasmin-antiplasmin complex and D-dimer was greater after six cycles of treatment in the trimegestone group compared with the dydrogesterone group. In conclusion, decreased levels of inhibitors of blood coagulation and increased thrombin production were found in both groups however a greater increase in the levels of plasmin-antiplasmin complex and D-dimer was found in the trimegestone group. This suggests an enhanced fibrinolytic response in this group. Further studies are required to determine the significance of this finding with respect to venous thrombosis risk. © 2008 Schattauer GmbH.