Oral but not transdermal estrogen replacement therapy reduced level of tissue factor pathway inhibitor: cross-over designed study.

OBJECTIVES: The purpose of the present study was to determine changes of biochemical risk factors of thromboembolism especially of TFPI during the use of oral versus transdermal administration of early estrogen replacement therapy.

METHODS: In a 12-week prospective, randomized, cross-over trial, oestradiol was administered orally in a dose of 2 mg daily or transdermally in an equivalent dose of 0.05 mg daily. Forty-five healthy early postmenopausal women were included into the study within 12 weeks after the hysterectomy and ovariectomy (surgical castration). Forty-one women completed the study and their data were analyzed. The average age was of 49+/- 6 years.

RESULTS: After an oral therapy, the average value of TFPI decreased significantly (p < 0.0001) from 87.5 +/- 38.5 ng/ml to 68 +/- 37 ng/ml but remained stable in transdermal group (81.9 +/- 36.8 ng/ml). No significant changes occurred in D-dimers. In both groups AT-III and fibrinogen decreased without exceeding their physiological ranges.

CONCLUSIONS: The oral therapy reduced significantly TFPI levels compared to transdermal route of administration. The results confirm more pronounced impact of oral estrogen on hemostasis variables.