Human Reproduction, Vol. 17, No. 12, 3235-3241,
December 2002
© 2002 European Society of Human Reproduction and Embryology
Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor
1 Department for Thrombosis Research, University of Southern Denmark and 2 Department of Clinical Biochemistry, Ribe County Hospital in Esbjerg, DK-6700, 3 Department of Obstetrics and Gynecology, Frederiksberg Hospital, DK-2000, 4 Rigshospitalet DK-2100 and 5 Gentofte Hospital DK-2900 and 6 University of Copenhagen, DK-2000, Denmark
BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i) cyclic oral estrogen/progestin (n = 25); (ii) long-cycle oral estrogen/quarterly progestin (n = 32); (iii) continuous oral estrogen/progestin (n = 21); (iv) continuous oral estrogen/intrauterine progestin (n = 22); (v) no HRT (n = 26). Blood was collected at baseline, 3, 6 and 12 months. Additional sampling was done before progestin intake in the long cycle group. RESULTS: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed after progestin intake. The integrated response, AUC, for TFPI was significantly lower in the HRT groups compared with the reference group. CONCLUSION: The observed changes may increase the early thrombotic risk associated with HRT use.
Key words: factor VII/HRT/progestins/randomized study/TFPI
7 To whom correspondence should be addressed at: Department of Clinical Biochemistry, Ribe County Hospital, Østergade 80,DK-6700 Esbjerg, Denmark. E-mail: emb{at}ribeamt.dk
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