ABSTRACT
We conducted a dose-response study in 23 postmenopausal women to compare the physiologic effects of transdermal estradiol and oral conjugated equine estrogens. The doses studied were 25, 50, 100, and 200 micrograms of transdermal estradiol per 24 hours, and 0.625 and 1.25 mg of oral conjugated estrogens. Transdermal estradiol increased circulating concentrations of estradiol and estrone. Oral conjugated estrogens also raised the levels of estrogen, particularly estrone. Both preparations lowered gonadotropin levels, decreased the percentages of vaginal parabasal cells, increased the percentage of superficial cells, and lowered urinary calcium excretion. The effects of 0.625 and 1.25 mg of oral estrogens were similar to those of 50 and 100 micrograms of transdermal estradiol per 24 hours, respectively. Oral estrogens significantly increased circulating levels of renin substrate, sex-hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin; transdermal estradiol had no effect. The higher dose of oral estrogens had favorable effects on concentrations of low-density and high-density lipoproteins, but transdermal estradiol did not. Neither preparation affected any of the four clotting factors studied. These data indicate that transdermal estradiol can elicit many of the desirable actions of estrogen while avoiding the pharmacologic effects of oral estrogens on hepatic proteins.
Subject(s)
Estradiol/administration & dosage , Administration, Oral , Administration, Topical , Blood Coagulation Factors/analysis , Calcium/urine , Carrier Proteins/blood , Creatine/urine , Estradiol/blood , Estrogens, Conjugated (USP)/administration & dosage , Estrone/blood , Female , Follicle Stimulating Hormone/blood , Humans , Hydroxyproline/urine , Lipids/blood , Luteinizing Hormone/blood , Menopause , Sex Hormone-Binding Globulin/analysis , Skin , Thyroxine-Binding Proteins/analysis , Vaginal SmearsSubject(s)
Fibrinolytic Agents/pharmacology , Hemorrhage/chemically induced , Animals , Blood Coagulation Factors/analysis , Blood Coagulation Tests , Blood Platelets/drug effects , Drug Evaluation , Fibrin/metabolism , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/metabolism , Fibrinolysin/adverse effects , Fibrinolysin/pharmacology , Fibrinolysin/therapeutic use , Fibrinolytic Agents/adverse effects , Fibrinolytic Agents/therapeutic use , Humans , Myocardial Infarction/drug therapy , Plasminogen Activators/adverse effects , Plasminogen Activators/pharmacology , Plasminogen Activators/therapeutic use , Streptokinase/adverse effects , Streptokinase/immunology , Streptokinase/pharmacology , Streptokinase/therapeutic use , Thrombin/adverse effects , Thrombin/pharmacology , Thrombin/therapeutic use , Thromboembolism/drug therapySubject(s)
Blood Coagulation , Fibrinogen/metabolism , Fibrinolysis , Pregnancy , Chromatography/methods , Female , Fibrin/biosynthesis , Humans , Molecular Weight , Postpartum PeriodABSTRACT
Two hundred twenty patients admitted to a Coronary Care Unit were studied by serial plasma fibrinogen chromatography--a method for quantification of HMWFCs, native fibrinogen, and other fibrinogen derivatives in plasma. Enhanced formation of fibrin (intravascular coagulation/thrombosis) is reflected by elevation of plasma HMWFC. One hundred ten patients suffering from documented acute myocardial infarction showed early, sharp elevation of plasma HMWFC (p less than 0.001 when compared to normal and cardiac control groups), a finding which persisted for 10 to 20 days after infarction. Forty-three of the patients did not receive anticoagulant therapy, and the others received either initial heparin, heparin plus warfarin, or werfarin therapy. Plasma fibrinogen chromatographic findings, days 1 to 5, did not differ between the anticoagulated and nonanticoagulated treatment groups, although there were minor differences in the data for days 6 to 10. The results demonstrate that patients with acute myocardial infarction develop a coagulopathy characterized by enhanced fibrin formation, which is influenced to only a minor degree by conventional dosage anticoagulant therapy.
Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/physiopathology , Myocardial Infarction/physiopathology , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/drug therapy , Fibrinogen/metabolism , Heart Failure/complications , Heart Failure/drug therapy , Heart Failure/physiopathology , Heparin/therapeutic use , Humans , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Warfarin/therapeutic useSubject(s)
Chromatography, Agarose , Chromatography, Gel , Fibrinogen/metabolism , Postoperative Complications/blood , Radionuclide Imaging , Thrombophlebitis/blood , Adolescent , Adult , Aged , Antithrombins/metabolism , Aspirin/administration & dosage , Humans , Iodine Radioisotopes , Middle Aged , Neoplasms/blood , Neoplasms/surgery , Plasminogen/metabolism , alpha 1-Antitrypsin/metabolism , alpha-Macroglobulins/metabolismABSTRACT
A new procedure, plasma fibrinogen chromatography, has been utilized, together with other blood coagulation assays, to quantify fibrin formation in 43 children with acute poststreptococcal glomerulonephritis (AGN) from the time of hospitalization until recovery. During the prediuretic phase of AGN, significant evidence for substantial increase in fibrin formation (intravascular coagulation) included gross increase in plasma high molecular weight fibrinogen complexes (HMWFC), the development of either hypo- or hyperfibrinogenemia and gross depression of coagulation factor XIII concentration and of alpha2-macroglobulin concentration. During the diuretic phase of the disease, these abnormalities regressed and evidence of enhanced plasma fibrinolytic activity, documented by an increase in fibrinogen first derivative, was detected. Concomitantly, urinary excretion of fibrin(ogen) degradation products (FDP) underwent substantial increase. With disease recovery, which occurred in all children, urinary FDP excretion ceased and all coagulation findings normalized.