Conventional-dose hormone therapy (HT) and tibolone, but not low-dose HT and raloxifene, increase markers of activated coagulation

Abstract 

Objectives

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 1mg 17β-estradiol+0.5mg norethisterone acetate (NETA) (n=50), conventional-dose HT containing 2mg 17β-estradiol and 1mg NETA (n=50), 2.5mg tibolone (n=51), or 60mg 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.

Keywords: Hormone therapy (HT), Tibolone, Raloxifene, Venous thromboembolism (VTE), Coagulation, Clinical trial