A randomized, placebo-controlled trial of the effects of continuous combined hormone replacement therapy on coagulation and fibrinolytic systems in healthy postmenopausal women.
OBJECTIVE
To investigate the effects of combined hormone replacement therapy (HRT) on various parameters of coagulation and fibrinolysis that may contribute to increased risk for venous thromboembolic events.


METHODS
Prospective, randomized, double-blind, placebo-controlled study.


METHODS
Academic hospital.


METHODS
Sixty-one healthy postmenopausal women with intact uterus.


METHODS
Patients were randomized to receive continuous combined HRT (estradiol, 2 mg/d, and norethisterone acetate, 1 mg/d) or placebo for 6 months.


METHODS
Markers of coagulation and fibrinolysis were measured before therapy and after 3 and 6 months of therapy.


RESULTS
The groups did not differ significantly in levels of prothrombin fragments 1 and 2 and thrombin-antithrombin III complex after 3 and 6 months of therapy. After 6 months of HRT, significant decreases in activity of antithrombin III and protein C and levels of plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, and euglobulin clot lysis time and a significant increase in D-dimer level were found compared with placebo.


CONCLUSIONS
Continuous combined HRT for several months produced no net activation of coagulation but improved fibrinolysis in healthy postmenopausal women with no risk factors for venous thromboembolic events.
Salobir
Barbara Guzic
BG
University Medical Center, Ljubljana, Slovenia. barbara.guzic@tmovo.kclj.si
Keber
Irena
I
Vrabic
Lucija
L
D001777:Blood Coagulation / Q000187:drug effects*; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077563:Norethindrone Acetate; D017698:Postmenopause / Q000502:physiology*; D012016:Reference Values
D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone