Transdermal estrogen therapy effects on fibrinogen levels in women with a past history of venous thromboembolism: a pilot study.

OBJECTIVE: To evaluate thromboelastographic parameters and fibrinogen levels in women treated with transdermal 17beta estradiol. METHODS: 29 menopausal women with a history of venous thromboembolic disease were included. Nine patients composed the treatment (HT) group and 20 the control group. Coagulation was assessed by thromboelastography in samples of whole blood and platelet-poor plasma (PPP). The following thromboelastographic variables were measured: time for initial coagulation (R), blood clotting speed (K and the alpha angle), clot tensile strength (MA and G), global index of coagulation (CI) and fibrinolysis (LY30) and fibrinogen levels. RESULTS: There were no differences in the other parameters comparing both groups. Fibrinogen levels showed a 13.77 +/- 19.94% reduction in the HT group and a 5.51 +/- 8.09% increase in the control group after 6 months. CONCLUSIONS: Our data suggested that transdermal estrogen may not increase blood coagulability, but that it reduces fibrinogen levels in HT women.

Hormone therapy in Brazilian postmenopausal women with chronic hepatitis C: a pilot study.

OBJECTIVE: To evaluate liver function and hemostatic parameters in postmenopausal women who have chronic infection with the hepatitis C virus and climacteric symptoms and are undergoing hormone therapy (HT) (standard dose of transdermal continuous combined hormone therapy). DESIGN: Fifty out of 336 postmenopausal patients with chronic infection with the hepatitis C virus were selected. The non-inclusion criteria were other chronic or systemic liver diseases, severe vascular diseases, autoimmune diseases or malignant tumors. The patients were randomized into two groups: the HT group with 25 patients to be given transdermal hormone therapy (50 microg estradiol plus 170 microg norethisterone/day) and the control group with the other 25 patients (no medication). Hepatic tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total alkaline phosphatase, albumin, serum bilirubin) and hemostatic parameters (prothrombin time, factor V, fibrinogen) were evaluated at baseline and at 1, 4, 7 and 9 months of treatment. RESULTS: No significant changes in parameters were found in the comparison between the treated group and the controls, except for a decrease in total alkaline phosphatase (p = 0.002), presumably due to changes in bone remodelling. CONCLUSIONS: There were no changes in liver function after a 9-month treatment with transdermal estradiol plus norethisterone in symptomatic postmenopausal patients with hepatitis C.

Effects of lopinavir-ritonavir combined therapy during the rat pregnancy. Morphological and biochemical aspects.

OBJECTIVE: To evaluate the biochemical and morphological effects in rats subjected to three different dose associations of the protease inhibitors lopinavir and ritonavir administered throughout the entire period of pregnancy. STUDY DESIGN: The animals were treated throughout pregnancy with daily oral doses of lopinavir+ritonavir starting at the day one of pregnancy, and were divided into four groups: E1, 13.3+3.3 mg/kg; E2, 39.9+9.9 mg/kg; E3, 119.7+29.9 mg/kg and C, control (drug vehicle, propyleneglycol). The animals were then sacrificed and maternal blood and fetal and maternal organ samples were taken for morphological and biochemical analysis. RESULTS: No major changes were identified in the group treated with the lowest dose as compared with the control. In the group E2, we found hepatocytes with signs of atrophy, eosinophilic cytoplasm, picnotic nuclei and vasodilatation. The proximal convoluted tubules of maternal kidneys showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. In the group treated with the highest dose (group E3), in the maternal kidneys and livers, the morphological changes were similar to those found in E2, although more prominent. Regarding the fetal organs, the single abnormality observed was some liver vasodilation in the group E3 (highest dose). The treatment with lopinavir+ritonavir caused discrete, yet significant, alterations of aspartate aminotransferase activity, blood urea nitrogen and creatinine plasma levels. CONCLUSIONS: Our results showed that the administration of a combination of lopinavir plus ritonavir to pregnant rats can cause morphological as well as functional changes in maternal and fetal liver and kidneys and, in higher than therapeutic doses, might be toxic to those animals.