Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor.
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.


CONCLUSIONS
The observed changes may increase the early thrombotic risk associated with HRT use.
Bladbjerg
E M
EM
Department for Thrombosis Research, University of Southern Denmark, Denmark. emb@ribeamt.dk
Skouby
S O
SO
Andersen
L F
LF
Jespersen
J
J
D008078:Cholesterol, LDL / Q000097:blood; D017373:Cyproterone Acetate / Q000009:adverse effects; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005167:Factor VII / Q000032:analysis*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage; D008074:Lipoproteins / Q000097:blood*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D010919:Placebos; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage* / Q000009:adverse effects*; D012307:Risk Factors; D013927:Thrombosis / Q000139:chemically induced*; D013997:Time Factors; D014599:Uterus / Q000187:drug effects
D008078:Cholesterol, LDL; D008074:Lipoproteins; D010919:Placebos; D011372:Progestins; C051928:lipoprotein-associated coagulation inhibitor; D017373:Cyproterone Acetate; D004958:Estradiol; D016912:Levonorgestrel; D005167:Factor VII; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone