BACKGROUND The purpose of the present study was to determine changes of plasminogen activator inhibitor-1 (PAI-1) as biochemical cardiovascular risk factor during the use of different administration methods in the early estrogen replacement therapy. METHODS AND RESULTS In a 12-week prospective, randomized, interventional, cross-over trial, oestradiol was administered orally in a dose of 2 mg daily or transdermally in a dose of 0.05 mg daily. Forty-five healthy 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. PAI-1 was determined by bioimmunoassay (Chromolyze PAI-1). The PAI-1 level decreased statistically significantly (p = 0.001) after the oral oestrogen therapy from 11.39 +/- 12.02 IU/l to 5.0 +/- 5.27 IU/l. Changes are also significant compared with non-significant changes after the transdermal therapy. CONCLUSIONS The oral therapy reduced statistically significantly PAI-1 levels compared with the transdermal method of administration. This change is beneficial from the view of cardiovascular risk.