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. Design: A pilot, nonrandomized study. Setting: Healthy volunteers in an academic research environment. Patient(s): Postmenopausal women. Intervention(s): Eight women were treated with 17beta-estradiol from three vaginal rings, releasing 7.5 mug per ring for a total of 22.5 mug over 24 hours. The rings were changed every morning for 14 days. Main Outcome Measure(s): Hemostatic changes were recorded. Result(s): 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 mug per 24 hours.