Hemostatic markers in healthy postmenopausal women during intranasal and oral hormone therapy: a randomized trial.
OBJECTIVE
To study changes in the hemostatic balance during intranasal compared with oral administration of 17beta-estradiol (E2) and norethisterone (NET) or NET acetate in postmenopausal women. A wide range of markers of coagulation and fibrinolysis associated with coronary artery disease was tested.


METHODS
In a two-center, randomized, double-blind, comparative trial, 90 healthy postmenopausal women (aged 56.6 +/- 4.7 y) received daily continuous combined hormone therapy, either E2/NET 175 microg/275 mug intranasally as a spray (n = 47) or E2/NET acetate 1 mg/0.5 mg orally as a capsule (n = 43) for 1 year. Hemostatic markers were measured in blood samples taken at baseline and after 12, 24, and 52 weeks of treatment.


RESULTS
After 52 weeks of treatment, changes in the intranasal group in markers of coagulation-fibrinogen (-1.3%), factor VII activity (-14.0%), and prothrombin fragment 1 + 2 (+5.8%)-were significantly less (P < 0.05) than the changes in the oral group for these parameters (-6.5%, -20.3%, and +19.0%, respectively). Changes in activated factor VII did not differ between the groups. Neither group showed significant changes in thrombin-antithrombin complex. In the intranasal group, decreases in markers of fibrinolysis-tissue-type plasminogen activator (-10.4%) and plasminogen activator inhibitor-1 antigen (-13.8%)-were significantly less (P < 0.05) than the decreases in the oral group (-17.8% and -38.0%, respectively). A decrease in plasminogen activator inhibitor-1 activity and increases in D-dimer and plasmin-alpha2-antiplasmin complex did not differ between the groups. No differences were found between the groups in homocysteine, which overall was unaltered in both groups.


CONCLUSIONS
During intranasal E2/NET therapy, changes in the coagulatory and fibrinolytic markers were to some extent less than those observed during oral therapy.
Hemelaar
Majoie
M
Vrije Universiteit , Amsterdam, The Netherlands.
Kenemans
Peter
P
Hack
C Erik
CE
Klipping
Christine
C
van der Mooren
Marius J
MJ
D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects*; D013927:Thrombosis / Q000139:chemically induced
D004958:Estradiol; D009640:Norethindrone