The differential effect of estrogen, estrogen-progestin and tibolone on coagulation inhibitors in postmenopausal women.
OBJECTIVE
Hormone therapy increases the risk of venous thromboembolism, possibly through a negative effect on coagulation inhibitors. The aim of the study was to assess the effect of conjugated equine estrogens alone or in combination with medroxyprogesterone acetate, low-dose 17beta-estradiol combined with norethisterone acetate and tibolone on inhibitors of coagulation.


METHODS
Two hundred and sixteen postmenopausal women received orally either conjugated equine estrogens 0.625 mg (CEE, n=24) or tibolone 2.5 mg (n=24) or CEE+medroxyprogesterone acetate 5 mg (CEE/MPA, n=34) or 17beta-estradiol 1 mg+norethisterone acetate 0.5 mg (E2/NETA, n=66) or no therapy (control, n=68) for 12 months. Plasma antithrombin, protein C and total protein S were measured at baseline and at 12 months.


RESULTS
CEE, CEE/MPA and E2/NETA treatment were associated with a significant decrease in antithrombin levels (CEE: baseline 235.6+/-47.6 mg/l, follow-up 221.3+/-48.3 mg/l, p=0.0001; CEE/MPA: baseline 251.1+/-38.6 mg/l, follow-up 225.0+/-42.6 mg/l, p=0.009; E2/NETA: baseline 257.1+/-59.4 mg/l, follow-up 227.1+/-50.4 mg/l, p=0.007; tibolone: baseline 252.6+/-62.4 mg/l, follow-up 261.9+/-59.1 mg/l, p=0.39). Protein C decreased significantly in the CEE and CEE/MPA groups (CEE: baseline 3.64+/-1.17 mg/l, follow-up 2.48+/-1.47 mg/l, p=0.004; CEE/MPA: baseline 3.24+/-1.23 mg/l, follow-up 2.61+/-1.38 mg/l, p=0.001; E2/NETA: baseline 3.24+/-1.10 mg/l, follow-up, 3.15+/-1.11 mg/l, p=0.08; tibolone: baseline 3.26+/-1.25 mg/l, follow-up 3.09+/-1.32 mg/l, p=0.37). Protein S decreased significantly only in the CEE/MPA group (CEE: baseline 19.4+/-2.76 mg/l, follow-up 18.0+/-2.45 mg/l, p=0.56; CEE/MPA: baseline 18.4+/-3.42 mg/l, follow-up 14.5+/-3.43 mg/l, p=0.005; E2/NETA: baseline 19.0+/-3.11 mg/l, follow-up 19.5+/-3.43 mg/l, p=0.18; tibolone: baseline 18.5+/-3.09 mg/l, follow-up 18.0+/-4.09 mg/l, p=0.32).


CONCLUSIONS
Estrogen and estrogen-progestin therapy are associated with a reduction in coagulation inhibitors, the extent of which depends on the regimen administered. Tibolone appears to have no effect on inhibitors of coagulation.
Keramaris
N C
NC
Vascular Clinic, 1st Department of Surgery, University of Athens Medical School, Laikon Hospital, Athens, Greece.
Christodoulakos
G E
GE
Lambrinoudaki
I V
IV
Dalamanga
A
A
Alexandrou
A P
AP
Bramis
J
J
Bastounis
E
E
Creatsas
G C
GC
D000704:Analysis of Variance; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage; D045166:Estradiol Congeners / Q000008:administration & dosage* / Q000494:pharmacology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage* / Q000494:pharmacology; D013923:Thromboembolism / Q000209:etiology; D020246:Venous Thrombosis / Q000209:etiology
D001779:Blood Coagulation Factors; D045166:Estradiol Congeners; D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D004958:Estradiol; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; C027385:tibolone; D009640:Norethindrone