Effects of isoflavones on the coagulation and fibrinolytic system of postmenopausal women.

OBJECTIVE: We evaluated the effects of soy isoflavone supplementation on hemostasis in healthy postmenopausal women. METHODS: In this double-blinded, placebo-controlled study, 47 postmenopausal women 47-66 y of age received 40 mg of soy isoflavone (n = 25) or 40 mg of casein placebo (n = 22) once a day for 6 mo. Levels of factors VII and X, fibrinogen, thrombin-antithrombin complex, prothrombin fragments 1 plus 2, antithrombin, protein C, total and free protein S, plasminogen, plasminogen activator inhibitor-1, and D-dimers were measured at baseline and 6 mo. Urinary isoflavone concentrations (genistein and daidzein) were measured as a marker of compliance and absorption using high-performance liquid chromatography. Baseline characteristics were compared by unpaired Student's t test. Within-group changes and comparison between the isoflavone and casein placebo groups were determined by a mixed effects model. RESULTS: The levels of hemostatic variables did not change significantly throughout the study in the isoflavone group; however, the isoflavone group showed a statistically significant reduction in plasma concentration of prothrombin fragments 1 plus 2; both groups showed a statistically significant reduction in antithrombin, protein C, and free protein S levels. A significant increase in D-dimers was observed only in the isoflavone group. Plasminogen activator inhibitor-1 levels increased significantly in the placebo group. However, these changes were not statistically different between groups. CONCLUSION: The results of the present study do not support a biologically significant estrogenic effect of soy isoflavone on coagulation and fibrinolysis in postmenopausal women. However, further research will be necessary to definitively assess the safety and efficacy of isoflavone.

Hormone replacement therapy and hemostasis: effects in Brazilian postmenopausal women.

OBJECTIVE: To evaluate the impact that administration of transdermal estradiol gel combined with medroxyprogesterone acetate (MPA) has on hemostasis. METHODS: In this open prospective longitudinal study, thirty postmenopausal women received transdermal estradiol gel (1 mg/day) continuously combined with oral MPA (5 mg/day) for 12 days/month. The following parameters were determined: prothrombin time (PT), activated partial thromboplastin time (aPTT), factors VII, X, and XII activity, fibrinogen levels, thrombin-antithrombin complex levels, protein C and S antigen, antithrombin activity, plasminogen activator inhibitor type 1 (PAI-1) antigen, tissue-type plasminogen activator (t-PA) antigen, plasminogen activity and fibrin degradation products (FbDP) antigen. They were evaluated before and after 6 months of treatment. RESULTS: There was a significant decrease in factor VII activity (P=0.001), factor X activity (P=0.016), protein C antigen (P=0.022), antithrombin activity (P=0.025), plasminogen activity (P=0.023), t-PA antigen (P=0.043) and FbDP antigen (P=0.048) compared with baseline values. CONCLUSION: The results suggest that the treatment with transdermal estradiol gel combined with MPA avoids any major activation of coagulation and does not produce any overall effect on fibrinolysis. Therefore, this treatment might provide interesting effects on hemostasis in postmenopausal Brazilian women.

Efeitos do contraceptivo oral contendo 20ug de etinilestradiol e 150ug de desogestrel sobre os sistemas de coagulaçäo e fibrinóllise / Effects of the oral contendo 20ug of etinilestradiol e 150 ug of desogestral on the coagulation and fibrinolise systems

O uso de contraceptivos orais está associado a um risco aumentado de doenças tromboembólicas, o que pode ser explicado pelos seus efeitos sobre o sistema hemostático. Tem sido descrito que o uso de contraceptivos orais promovem alteraçöes pró-coagulantes, e que essas alteraçöes säo acompanhadas dos aumentos da atividade fibrinolítica e dos inibidores naturais da coagulaçäo, o que causaria um restabelecimento do equilíbrio hemostático. O objetivo deste estudo foi avaliar os efeitos do contraceptivo oral contendo 20 ug de etinilestradiol e 150 ug de desogestrelsobre os sistemas de coagulaçäo e fibrinólise. Participaram do estudo 11 voluntárias que foram avaliadas antes e após seis meses de uso do contraceptivo oral. Os parâmetros analisados foram: atividades dos fatores VII, VIII, IX, X e XII (plasmas deficientes em fatores com detecçäo foto-óptica do coágulo), atividades da antitrombina, plasminogênio e a2-antiplasmina (ensaios cromogênicos), quantificaçäo dos antígenos t-PA, produtos de degradaçäo da fibrina e proteínas C e S(ELISA), TP, TTPA e concentraçäo plasmática de fibrinogênico (detecçäo fotoóptica do coágulo). Observamos as seguintes alteraçöes estatisticamente significantes (nível de significância de p<0,05): aumento das atividades dos fatores VIII, IX, X e XII, reduçäo do TTPA, aumento da atividade do plasminogênio, aumento de proteína C e diminuiçäo de proteína S. Com esses resultados sugerimos que o uso do contraceptivo oral testado promove um estado pró-coagulante. Entretanto, os mecanismos de restabelecimento do equilíbrio hemostático näo podem ser garantidos, já que näo observamos alteraçöes suficientes que indiquem isso. Näo observamos aumento nos níveis dos produtos de degradaçäo da fibrina, o que indica que näo ocorreram alteraçöes na gênese e degradaçäo da fibrina. Portanto, sugerimos que o uso do contraceptivo oral pode aumentar o risco de doenças tromboembólicas, principalmente em associaçäo com outros fatores de riscos genéticos e/ou adquiridos.