Effects of tibolone and continuous combined hormone replacement therapy on parameters in the clotting cascade: a multicenter, double-blind, randomized study.
OBJECTIVE
To determine the effects of tibolone and continuous combined HRT (ccHRT) on parameters in the clotting cascade.


METHODS
Randomized, double-blind study.


METHODS
Hemostasis unit of a university hospital clinic in Germany.


METHODS
Sixty healthy postmenopausal women.


METHODS
Twenty-nine subjects were treated with tibolone (2.5 mg/d) and 31 with oral ccHRT containing estradiol (2 mg/d) + estriol (1 mg/d) + norethindrone acetate (1 mg/d).


METHODS
Effects on parameters in the clotting cascade at baseline and after 12 and 24 weeks of treatment.


RESULTS
Tibolone increased fibrinolysis parameters without significantly altering coagulation parameters. Treatment with ccHRT resulted in a stimulating effect on parameters of both fibrinolysis and coagulation. Tibolone showed a stronger reduction of factor VII activity; less reduction of AT-III, protein C activity, and protein S activity; stronger increase of the activated partial thromboplastin time, plasminogen and plasminogen-antiplasminogen complexes; and less increase of D-Dimer than ccHRT. Both preparations similarly reduced climacteric complaints, whereas tibolone showed less breast complaints than ccHRT.


CONCLUSIONS
This study confirms that tibolone, and to a lesser extent also ccHRT, changes hemostasis parameters toward a more fibrinolytic profile, which may diminish the risk of venous thrombosis.
Winkler
U H
UH
Hemostasis Unit, University Hospital of Essen, Germany. ulrich-horst.winkler@fek.de
Altkemper
R
R
Kwee
B
B
Helmond
F A
FA
Coelingh Bennink
H J
HJ
D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage / Q000627:therapeutic use*; D013923:Thromboembolism / Q000517:prevention & control*
D009652:Norpregnenes; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone