Title
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
Author
Norris, L.A.
Brosnan, J.
Bonnar, J.
Conard, J.
Kluft, C.
Hellgren, M.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
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.
Subject
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
To reference this document use:
http://resolver.tudelft.nl/uuid:be9308b1-ad9a-4748-af12-18d89fdb1ba4
DOI
https://doi.org/10.1160/th07-12-0746
TNO identifier
240938
ISSN
0340-6245
Source
Thrombosis and Haemostasis, 100 (2), 253-260
Document type
article