Conventional-dose hormone therapy (HT) and tibolone, but not low-dose HT and raloxifene, increase markers of activated coagulation.
OBJECTIVE
Hormone therapy (HT) is associated with a modest, but significantly increased risk for arterial and venous thromboembolism. We have compared the effects of estrogen, tibolone, and raloxifene on relevant markers of coagulation activation and investigated whether there is a dose-response relationship of oral HT.


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


RESULTS
The groups were comparable with regard to demographic characteristics and laboratory variables at baseline. D-dimer increased markedly in the conventional-dose HT group, but remained unchanged in the low-dose HT group. Tibolone was associated with a medium increase, whereas raloxifene was associated with a decrease in D-dimer levels. Changes in prothrombin fragment 1 + 2 showed a similar pattern for all four groups, whereas no significant differences in changes of thrombin-antithrombin complex were observed.


CONCLUSIONS
Our data suggest that low-dose HT is associated with less activation of coagulation than conventional-dose HT. This finding may be of clinical importance since randomized clinical trials showing increased risk of thrombosis have utilized conventional-dose HT.
Eilertsen
A L
AL
Department of Hematology, Ullevaal University Hospital Trust, Hematological Research Laboratory, NO-0407 Oslo, Norway. a.l.eilertsen@medisin.uio.no
Qvigstad
E
E
Andersen
T O
TO
Sandvik
L
L
Sandset
P M
PM
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage*; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D013923:Thromboembolism / Q000209:etiology
D018931:Antineoplastic Agents, Hormonal; D050071:Bone Density Conservation Agents; D009652:Norpregnenes; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone