Effect of the cessation of long-term hormone replacement therapy on plasma plasminogen activator inhibitor-1 and fibrinogen.
OBJECTIVE
Hormone replacement therapy (HRT) has generally been documented to reduce plasminogen activator inhibitor-1 (PAI-1) and fibrinogen levels in plasma of postmenopausal women. We used a wash out protocol to study whether stopping long-term HRT with estrogen alone or a combination of estrogen-progestin have different effects on these markers of hemostasis.


METHODS
Thirty healthy postmenopausal women on HRT participated. Fifteen had estradiol valerate, and 15 had estradiol valerate and levonorgestrel. Each was studied after long-term HRT (period 1), four weeks after cessation of the treatment (period 2, wash out), and three weeks after reintroducing the therapy (period 3).


RESULTS
In the estrogen group, PAI-1 increased by 18% during the wash out period (P=0.013) and decreased by 22% after reintroduction of therapy (P=0.001). In the combined therapy group, there was a trend of PAI-1 to increase by 18% when therapy was discontinued (P=0.17), and it decreased by 25% after reintroduction of hormone replacement therapy (P=0.036). Fibrinogen was initially lower in the estrogen group compared with the combined therapy group (p=0.014), and did not change during wash out.


CONCLUSIONS
This wash out study shows that cessation of long-term HRT unfavorably increases PAI-1, but appears to have no adverse effect on fibrinogen.
Kalela
Anne
A
Department of Medical Biochemistry, University of Tampere Medical School, FIN-33014, Tampere, Finland.
Jokela
Hannu
H
Lehtimäki
Terho
T
Uppa
Helena
H
Kunnas
Tarja
T
Teisala
Klaus
K
Punnonen
Reijo
R
Nikkari
Seppo T
ST
D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D017698:Postmenopause / Q000097:blood*
D004338:Drug Combinations; D017395:Plasminogen Activator Inhibitor 1; D004958:Estradiol; D016912:Levonorgestrel; D005340:Fibrinogen