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

Lucy A. Norris; Jeanette Brosnan; John Bonnar; Jacqueline Conard; Cornelius Kluft; Margareta Hellgren

doi:10.1160/TH07-12-0746

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(02): 253-260
DOI: 10.1160/TH07-12-0746

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

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

Lucy A. Norris

¹Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St James’s Hospital, Dublin, Ireland

,

Jeanette Brosnan

¹Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St James’s Hospital, Dublin, Ireland

,

John Bonnar

¹Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St James’s Hospital, Dublin, Ireland

,

Jacqueline Conard

²Hopital Hotel-Dieu, Service d’Hematologie Biologique, Notre Dame, Paris Cedex, France

,

Cornelius Kluft

³Gaubius Laboratory, TNO-PG, Leiden, The Netherlands

,

Margareta Hellgren

⁴Sahlgrenska Hospital, Dept. Obstetrics and Gynaecology, Goteburg and Bohus Count Primary Health Care Authority, Sweden

› Author Affiliations

Abstract

Summary

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 dydro-gesterone 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 tri-megestone 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.

Keywords

Hormones - haemostasis - venous thrombosis

Full Text

References

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