Hum. Reprod. Advance Access published online on January 4, 2007
Human Reproduction, doi:10.1093/humrep/del498
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
A comparative study of the effect of continuous combined conjugated equine estrogen plus medroxyprogesterone acetate and tibolone on blood coagulability
1 Department of Obstetrics and Gynecology, Frederiksberg Hospital 2 Department of Obstetrics and Gynecology, Hvidovre Hospital, University of Copenhagen, Denmark 3 Department for Thrombosis Research, Institute of Public Health, University of Southern Denmark, Esbjerg, Denmark 4 Department of Clinical Biochemistry, Ribe County Hospital, Esbjerg, Denmark
5 To whom correspondence should be addressed at: Department for Thrombosis Research, Institute of Public Health, University of Southern Denmark, Niels Bohrs Vej 9, DK-6700 Esbjerg, Denmark. Tel: +4579182415; Fax: +4579182430; E-mail: jsi{at}ribeamt.dk
BACKGROUND: Hormone therapy (HT) after the menopause is associated with increased risk of venous thromboembolism (VTE). Tibolone has pharmacodynamic properties different from other hormone preparations. We compared the effect of a combined HT and tibolone on the inhibition of haemostasis.
METHODS: Thirty-eight post-menopausal women were randomly assigned to 1.25 or 2.5 mg per day of tibolone or oral continuous combined conjugated equine estrogen plus medroxyprogesterone acetate (CEE/MPA). Inhibitors of haemostasis were measured at baseline and after 12 months.
RESULTS: Results from the two groups of women receiving tibolone were not significantly different and, to improve the power of the study, the two groups were merged. Higher concentration of protein S (1.16 versus 1.00 IU ml–1; P=0.005) and higher activated protein C resistance ratio (APC-R) (4.2 versus 3.65; P=0.04) were observed in the tibolone group than in the CEE/MPA group. Both doses of tibolone increased APC-R significantly (P<0.01). Tissue factor pathway inhibitor (TFPI) was lower in the CEE/MPA group than in the tibolone group (67.8 versus 79.9 ng ml–1; P=0.03). CEE/MPA reduced the concentration of antithrombin (P=0.002), protein S (P<0.001) and TFPI (P<0.001). Both preparations reduced the concentration of plasminogen activator inhibitor 1 (P<0.05).
CONCLUSIONS: Tibolone induces fewer pharmacological alterations on blood coagulability than CEE/MPA and has a potentially favourable effect on APC-R. This may translate into a corresponding low risk of VTE, as also indicated from the existing clinical data.
Key words: coagulation/conjugated equine estrogen/medroxyprogesterone acetate/tibolone/venous thromboembolism