Effects of vaginally administered high estradiol doses on hormonal pharmacokinetics and hemostasis in postmenopausal women.
OBJECTIVE
To study the effect of high doses of estradiol released from vaginal rings on the pharmacokinetics of hormones, and the long-term effect on hormones and hemostasis in postmenopausal women.


METHODS
A pilot, nonrandomized study.


METHODS
Healthy volunteers in an academic research environment.


METHODS
Postmenopausal women. Eight women were treated with 17 beta-estradiol from three vaginal rings, releasing 7.5 micro g per ring for a total of 22.5 micro g over 24 hours. The rings were changed every morning for 14 days.


METHODS
Hemostatic changes were recorded.


RESULTS
Estradiol was rapidly absorbed, and statistically significant increases in the levels were found after 15 minutes; C(max) was obtained after 1 hour and a steady state after 24 hours. No statistically significant changes were found in the levels of coagulation factors V, von Willebrand factor, and activated factor VII; nor were any changes observed for activated protein C resistance, coagulation inhibitors protein C, protein S, or plasminogen activator inhibitor-1. No indication of increased thrombin formation was demonstrated by analyses of prothrombin fragment 1+2, fibrin D-dimer, and soluble fibrin. CONCLUSION(S)No statistically significant changes in hemostasis were observed from the vaginal administration of estradiol using a dose equivalent to transdermal administration with a release rate of 100 micro g per 24 hours.
Hall
Gerd
G
Karoliniska Institutet, Stockholm, Sweden.
Blombäck
Margareta
M
Landgren
Britt Marie
BM
Bremme
Katarina
K
D000282:Administration, Intravaginal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D017698:Postmenopause / Q000502:physiology*
D004970:Estrone; D004958:Estradiol; C017296:estrone sulfate