title: Differential effects of conventional and low dose oral hormone therapy (HT), tibolone, and raloxifene on coagulation and fibrinolysis.
abstract: 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.
authors.affiliation: Department of Hematology, Ullevål University Hospital Trust, Oslo, Norway. a.l.eilertsen@medisin.uio.no
authors.forename: Anette Løken
authors.initials: AL
authors.lastname: Eilertsen
authors.forename: Leiv
authors.initials: L
authors.lastname: Sandvik
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Mowinckel
authors.forename: Trine Opstad
authors.initials: TO
authors.lastname: Andersen
authors.forename: Erik
authors.initials: E
authors.lastname: Qvigstad
authors.forename: Per Morten
authors.initials: PM
authors.lastname: Sandset
mesh_terms: 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
chemical_list: D004338:Drug Combinations; D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone