Changes in hemostatic variables induced by estrogen replacement therapy: comparison of transdermal and oral administration in a crossover-designed study.

AIM: The purpose of this study was to determine the changes of biochemical risk factors for thromboembolisms using different administration routes of early estrogen replacement therapy.

METHODS: In a 12-week prospective, randomized crossover trial, estradiol was administered orally (2 mg daily) or transdermally (0.05 mg daily). Forty-five healthy early postmenopausal women were included into the study within 12 weeks after hysterectomy and oophorectomy. Forty-one women (age 49 +/- 6 years) completed the study, and their data were analyzed. The hemocoagulation parameters were determined prior to beginning of the study and at the end of each treatment period, separated by a 1-week washout period.

RESULTS: After oral therapy, the average tissue factor pathway inhibitor levels decreased statistically significantly (p < 0.0001) from 87.5 +/- 39.1 to 68 +/- 37.49 ng/ml. The plaminogen activator inhibitor-1 levels also decreased statistically significantly (p = 0.001) after the oral estrogen therapy from 11.39 +/- 12.02 to 5.0 +/- 5.27 IU/l. These changes were also significant when compared with the nonsignificant changes after the transdermal therapy. No significant changes occurred in the levels of D-dimers. After both treatment methods, the antithrombin III and fibrinogen levels decreased, but within their physiological ranges.

CONCLUSIONS: Oral administration of estrogen statistically significantly reduced the tissue factor pathway inhibitor and plasminogen activator inhibitor-1 levels when compared with the transdermal route. These changes cannot be unambiguously considered risky, and the zero change of D-dimers suggests that there was no activation of the coagulation cascade. We consider the neutral effect of the transdermal therapy more beneficial.