Effects of raloxifene and continuous combined hormone therapy on haemostasis variables: a multicenter, randomized, double-blind study.
BACKGROUND
Hormone replacement therapy is known to increase the risk of thromboembolic events. We compared the effects of HRT and raloxifene on some haemostasis variables.


METHODS
In a multicenter, double-blind study, 54 healthy postmenopausal women were randomized to receive either continuous treatment with 2 mg 17beta-estradiol plus 1 mg norethisterone acetate (n=30) or 60 mg raloxifene (n=24) daily for 12 months. Blood samples were collected at baseline and at 3, 6 and 12 months to evaluate therapy effects on some haemostasis variables (factor VII, factor VIII, prothrombin fragments 1 and 2, protein C, protein C activity, protein S, thrombin-antithrombin complex, D-dimer, antithrombin, fibrinogen and plasminogen activator inhibitor).


RESULTS
Both raloxifene and continuous combined hormone therapy modified the haemostasis variables toward a more prothrombotic profile. Factor VIII (p<0.01) and fibrinogen (p<0.05) plasma levels significantly increased at 6 months, prothrombin fragments 1 and 2 (p<0.05) significantly increased at 12 months, whereas protein C activity (p<0.001) and antithrombin (p<0.01) significantly decreased at 12 months in both groups.


CONCLUSIONS
Our results demonstrate that raloxifene and continuous combined hormone therapy exhibit the same prothrombotic profile. Both treatments induced an increase in procoagulant parameters at 6 months and a decrease in anticoagulant parameters at 12 months.
Sgarabotto
Mariapaola
M
Department of Obstetrics, Gynecologic and Neonatology. Parma University-Italy, v. Gramsci 14, Parma, Italy. M.Sgarabotto@libero.it
Baldini
Monica
M
Dei Cas
Alessandra
A
Manotti
Cesare
C
Luciana Barilli
Angela
A
Rinaldi
Maurizio
M
Benassi
Luigi
L
Bacchi Modena
Alberto
A
D000368:Aged; D015992:Body Mass Index; D003280:Contraceptives, Oral, Synthetic / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D004958:Estradiol / Q000627:therapeutic use*; D004964:Estriol / Q000627:therapeutic use; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077563:Norethindrone Acetate; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013997:Time Factors
D003280:Contraceptives, Oral, Synthetic; D004338:Drug Combinations; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol; C032040:Trisequens; D000077563:Norethindrone Acetate; D004964:Estriol; D009640:Norethindrone