Differential effects of conventional and low dose oral hormone therapy (HT), tibolone, and raloxifene on coagulation and fibrinolysis.
BACKGROUND
We have recently reported that different hormone regimens given to healthy post-menopausal women had markedly different effects on activation of coagulation. Low-dose hormone therapy (HT) and raloxifene, as opposed to conventional-dose HT and tibolone, were associated with no or minor activation of coagulation. The aim of this study was to elucidate the mechanism(s) for differences in coagulation activation by analysing clotting and fibrinolytic factors and coagulation inhibitors.


METHODS
202 healthy women were randomly assigned to receive treatment for 12 weeks with either low dose HT containing 1 mg 17 beta-estradiol+0.5 mg norethisterone acetate (NETA) (n=50), conventional dose HT containing 2 mg 17 beta-estradiol and 1 mg NETA (n=50), 2.5 mg tibolone (n=51), or 60 mg raloxifene (n=51) in an open-label design.


RESULTS
The conventional-and low-dose HT groups generally showed similar effects, i.e., reductions in both clotting factors and inhibitors, but the effects were markedly more pronounced in the conventional-dose HT group. Compared with the low-dose HT group those treated with tibolone showed more pronounced decreases in factor VII, less reduction of antithrombin and protein C and even increased levels in protein S and tissue factor pathway inhibitor. As opposed to the low-dose HT group the reductions in inhibitors in the raloxifene group were smaller. Moreover in those allocated to raloxifene reduced levels of fibrinogen were seen.


CONCLUSIONS
Our study demonstrates that the different HT regimens and raloxifene exert differential effects on coagulation factors, inhibitors and fibrinolytic factors.
Eilertsen
Anette Løken
AL
Department of Hematology, Ullevål University Hospital Trust, Oslo, Norway. a.l.eilertsen@medisin.uio.no
Sandvik
Leiv
L
Mowinckel
Marie Christine
MC
Andersen
Trine Opstad
TO
Qvigstad
Erik
E
Sandset
Per Morten
PM
D000284:Administration, Oral; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage* / Q000009:adverse effects; D017698:Postmenopause / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D013997:Time Factors
D004338:Drug Combinations; D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone