Changes in hemostatic variables induced by estrogen replacement therapy: comparison of transdermal and oral administration in a crossover-designed study.
OBJECTIVE
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.
Fait
Tomas
T
Department of Obstetrics and Gynecology, General Faculty Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic. tfait@seznam.cz
Vrablik
Michal
M
Zizka
Zdenek
Z
Kostirova
Milada
M
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D018592:Cross-Over Studies; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006487:Hemostasis; D006801:Humans; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood*
D004967:Estrogens; D017395:Plasminogen Activator Inhibitor 1; D004958:Estradiol; D000990:Antithrombin III; D005340:Fibrinogen