Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4 studies involving a combined oral contraceptive devised with norgestimate as the progestin and low-dose ethinyl estradiol as the estrogen, designed to have virtually no androgenic effects, are reviewed. A study of lipid metabolism found that cholesterol rose above desirable limits of 200 mg/dl in only 5% of women and fell within these limits in 25% who surpassed it. Similarly, triglycerides rose above 150 mg/dl in 5% with normal levels and fell in 28% who initially had high levels. 2 other studies documented increases in HDL and decreases in LDL, improving the HDL/LDL ratio. Coagulation factors were followed in a small series: no adverse effects on fibrinopeptide A, antithrombin III, protein C, Fibrinogen, factor VII, or factor VIII were seen in 6 months. No significant changes in mean levels of fasting glucose, insulin, hemoglobin A1C, or glucose tolerance were found. 2% of 2738 women developed abnormal fasting glucose levels after 6 months, while 35% lowered their initially abnormal glucose levels into the normal range after 6 months on the combined pill. Androgenicity was assessed by sex hormone binding globulin (SHBG) and free testosterone levels. The norgestimate pill elevated SHBG about 3-fold, lowering free testosterone. The prevalence of acne in norgestimate pill users is 2%. No change was noted in average blood pressure or weight. Similar results have been reported in studies on a triphasic norgestimate formulation. These results are optimistic for beneficial effects on major risk factors for cardiovascular disease, but large longterm epidemiological studies will have to be done to confirm them.
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PMID:Long-term profile of a new progestin. 136 89

Researchers have found that oral contraceptives (OCs) change carbohydrate and lipoprotein metabolism and these changes are like those linked with increased risk of cardiovascular (CV) disease, especially myocardial infarction and stroke. Since CV disease is the major cause of death in US women, it is important that OCs not induce changes in carbohydrate and lipoprotein metabolism. A new progestin, norgestimate, has an advantage over other progestins in that it tends not to induce male traits. This is beneficial because androgenicity is related to atherosclerosis which increases the risk of myocardial infarction. Further studies show that the new combined OC (250 mcg norgestimate/35 mcg ethinyl estradiol) does not influence serum glucose tolerance levels. It also does not affect the physiologic regulating system of prostacyclin, the inhibitor of platelet aggregation, by high density lipoprotein (HDL). In addition, it increases prostacyclin metabolites and HDL which may indeed decrease the risk of occlusive thrombotic vascular diseases. Moreover a study in Germany demonstrates that it causes no changes in fibrinopeptide A,m the anticoagulation factors antithrombin III and protein C, or coagulation promoting factors fibrinogen, factor VII, and the components of VIII. In women, it is absorbed well and metabolized extensively before the body eliminates it. Moreover this new combined OC has an overall Pearl index of 0.25. Studies to data indicate that norgestimate/ethinyl estradiol may be more advantageous than other OC formulations. Yet only long term epidemiologic studies can determine if it can indeed decrease the risk of CV diseases linked with older OCs.
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PMID:Norgestimate: a clinical overview of a new progestin. 160 87

6 patients with deep vein thrombosis triggered by drug therapy, that is oral contraceptives in 5 and the anticonvulsant tranexamic acid in 1, are described. These cases were among 40 symptomatic patients out of a total group of 81 with congenital coagulation inhibitor defects studied over 10 years at the Institute of Medical Semiotics, Padua, Italy. The 5 women with deep vein thrombosis ranged in age from 20-34, and had typically taken oral contraceptives containing 35 mcg ethinyl estradiol in combined or phasic preparations, for 1 to 8 cycles. One women, however, had been prescribed sequential pills containing 50 mcg mestranol. Another had taken oral contraceptives with impunity for 3 years, but developed deep vein thrombosis after taking tranexamic acid for 10 days. All recovered after heparin or oral anticoagulant therapy, except a 21 year old whose condition evolved into complete ileo-caval obstruction up to the renal veins, and was treated with urokinase. the congenital defects involved were 3 probable heterozygous true deficiencies of antithrombin III (low ATIII antigen and activity); a decreased protein C antigen to factor X antigen ratio; a heparin cofactor II deficiency; and a type I protein S deficiency (low free protein S, with normal total protein S and normal levels of C4B-bp.) While 5 of these 6 women had family histories of thromboembolic disease, the drug was prescribed without knowing that they were heterozygous for a coagulation inhibitor deficiency. The incidence of drug-induced thromboembolism was low in this series overall, where most of the events were triggered by surgery or trauma.
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PMID:The role of drugs, particularly oral contraceptives, in triggering thrombosis in congenital defects of coagulation inhibitors: a study of six patients. 178 39

The influence of low-dose oral contraceptives (OCs) on plasma levels of proteins C and S was investigated i 20 healthy women. These proteins, along with antithrombin III, are the most significant inhibitors of coagulation. Blood samples were collected after 6 months of treatment with an OC containing 30 mcg of ethinyl estradiol and either 150 mcg of desogestrel or 75 mcg of gestodene. A significant increase in functional protein C concentrations (from 55.70 + or - 9.84 to 117.48 + or - 21.29 in the desogestrel group and 68.80 + or - 19.11 to 135.60 + or - 28.66 in the gestodene group) was recorded between baseline and the 6-month measurement. There was a corresponding decrease in plasma concentrations of free protein S (from 98.48 + or - 9.64 to 73.96 + or - 12.07 in the desogestrel group and 104.79 + or - 31.52 to 83.14 + or - 18.28 in the gestodene group). Although these OC-induced changes were statistically significant, all values remained within the normal range. The differences between the 2 OC formulations were not significant. It is hypothesized that the changes in the active fraction of protein S recorded in OC users produce a procoagulant state and increases in protein C reflect an effort to compensate for this change. The findings that OC use increases protein C and decreases protein S values suggests that the two proteins differ in the regulation of their synthesis.
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PMID:Changes in the plasma levels of proteins C and S in young women on low-dose oestrogen oral contraceptives. 182 30

Several reports have appeared on the increased risk of thromboembolic diseases associated with the use of oral contraceptives (OCs). The increased risk of thromboembolism has been related to increased circulating blood levels of certain factors of both the clotting and fibrinolytic systems seen in OC users. These changes have been associated primarily with the estrogen component of the OC preparations. The two new oral contraceptives under study contain reduced levels of ethinyl estradiol, 30 micrograms and each utilizes a new progestogen--75 micrograms gestodene or 150 micrograms desogestrel. A prospective randomized study was performed with 50 women over one year in which several factors of the hemostatic system were investigated; blood samples were taken in treatment cycles 1, 3, 6 and 12 and 6-8 weeks after cessation of therapy. During treatment with both preparations, factors II, VII, IX, X, XI, XII, VIII clotting activity, and prekallikrein were elevated; factor V was not elevated. Antithrombin III which controls these factors, was decreased by 8-10% after 12 months; Protein C which controls factors V and VIII was not changed. Markedly elevated levels of plasminogen and its unaffected inhibitor alpha antiplasmin were seen in the first and all subsequent treatment cycles; this represents increased potency of the lytic system, which can be looked upon as a compensatory mechanism. There were no differences seen between the gestodene and desogestrel preparations regarding changes in the hemostatic system. As with all other low-dose pills, a history of thromboembolism is a contraindication to their use.
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PMID:Influence of modern low-dose oral contraceptives on hemostasis. 214 6

The effects of parenterally given polyestradiol phosphate (80 or 160 mg i.m. monthly) and bilateral subcapsular orchiectomy on blood coagulation and fibrinolytic parameters were compared in 11 patients with prostatic carcinoma. Estrogen therapy lowered antithrombin III, plasminogen and plasminogen activator inhibitor activities, whereas these parameters remained unchanged in orchiectomized patients. There were no significant changes in platelet count, fibrinogen, factor VII, protein C and alpha 2-antiplasmin in either group. Estrogen had unfavorable effects on hemostatic laboratory parameters in the direction of a hypercoagulable state. However, no thromboembolic complications were encountered.
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PMID:The effect of parenteral estrogen versus orchiectomy on blood coagulation and fibrinolysis in prostatic cancer patients. 217 41

The authors report their experience with 45 cases of inferior vena cava thrombosis. Diagnosis was delayed for an average of 55 days. One-third of cases were revealed by an embolic complication. Inflammatory diseases were the most common causes (Behcet disease: seven cases, systemic lupus erythematosus: 5 cases). Malignancies accounted for 20% of cases. Abnormalities of coagulation were uncommon: antithrombin III deficiency in one patient and protein C deficiency in another. Estrogen-progestogen combinations could be incriminated in 4 cases. Outcome was fatal in 20% of cases, usually as a result of the underlying disease. Functional status was good in two-thirds of patients without malignancy followed up for an average of 27 months. In 14 patients a clip was inserted to ensure total (3 cases) or partial (11 cases) interruption of vena cava blood flow because of a free thrombus and/or recurrent pulmonary embolism. Three patients had thrombectomy. After clip insertion two embolisms were recorded, one of which occurred in the immediate post-operative period.
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PMID:[Inferior caval syndromes. Apropos of 45 cases]. 632 Apr 31

The authors investigated sensitivity to activated protein C (APC) in 43 men, 42 women not using oral contraceptives (OCs), and 38 women using OCs containing 30.0-37.5 mcg ethinyl estradiol. A commercially available kit was used. Men were more sensitive to APC as compared with women not using OCs (p 0.005), but this difference seems not to be of clinical importance. Women using OCs were found to be significantly less sensitive to APC, reflected by a lower APC ratio, as compared with men (p 0.005) and women not using OCs (p 0.05). So, in normal individuals the APC sensitivity differs according to sex and estrogen intake. This should be taken into account when interpreting APC ratios.
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PMID:Sensitivity to activated protein C; influence of oral contraceptives and sex. 766 23

Clinicians followed 30 women, 18-37 years old, attending the family planning clinic of Falu Hospital in Sweden to compare the effect of a long interval of an oral contraceptive (OC) (30 mcg ethinyl estradiol + 150 mcg desogestrel) on the hemostasis system, lipid metabolism, and hormone binding proteins with that of a traditional 3-week regimen. They randomly allocated 20 women to the long-interval group (group I) and 10 to the 3-week group (group II). The long-interval consisted of 9 weeks taking the OC and 1 week not taking the OC. Between baseline and 12 months, sex hormone binding globulin (SHBG) levels increased 409% in group I (p .001) and 341% in group II (p .01). Corticosteroid binding globulin (CBG) levels increased 294% (p .001) for group I and 173% for group II. SHBG and CBG levels (markers of estrogenicity) were not significantly different between the 2 groups, however. Limited, insignificant changes took place with lipoprotein cholesterol fractions. VLDL-triglycerides and LDL-triglycerides increased significantly in group I (0.31-0.57 mmol/l) and group II (0.21-0.27 mmol/l) (p .05). Fibrinogen, factor VII, and thrombin/antithrombin III complex increased significantly in group I at 3 and 12 months. They had also increased in group II but not significantly. The coagulation inhibitors (i.e., antithrombin III, protein C, and protein S) remained virtually the same. Levels of tissue plasminogen activator antigen and tissue plasminogen activator inhibitor activity, both of the fibrinolytic system, fell (significant decrease only in group I). These findings show that the desogestrel-containing low-dose OC has limited effects on lipid metabolism, particularly the cholesterol subfractions, regardless of the regimen. It does increase minimally coagulation parameters, but the fibrinolytic system offsets this increase. In conclusion, the long-interval regimen is as safe as the 3-week regimen.
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PMID:Hemostasis profile and lipid metabolism with long-interval use of a desogestrel-containing oral contraceptive. 795 14

34 healthy women aged 21-30 years were assigned to 12 consecutive menstrual cycles of treatment with monophasic combinations. 15 women with a median age of 24 years received 20 mcg ethinyl estradiol (EE) and 150 mcg desogestrel (DSG) and 19 women with a median age of 23 years were treated with 30 mcg EE and 75 mcg gestodene (GST). Three women from the EE+DSG group and four women from the EE+GST group quit after six months because of personal reasons. Two more women from the EE+GST group quit after six months because of mammary tension and weight gain. Two women in each group smoked between one and ten cigarettes daily, the rest were nonsmokers. The evaluation of the hemostatic system was carried out in the luteal phase before the treatment began and within the last ten days in the third, sixth, and twelfth treatment cycle. In both groups plasma levels of fibrinogen (7.2 mcmol/l pretreatment to 8.7 mcmol/l posttreatment) and factor VIIc (80% pretreatment to 126% posttreatment) increased significantly under treatment, while the capacity of coagulation inhibition was affected after three months by increased protein C concentrations (15% in the EE+DSG group and 14% in the EE+GST group) and significantly decreased levels of protein C's cofactor, protein S levels by 11% and 15%, respectively. Increased fibrinolytic capacity was indicated by elevated activity and reduced antigen levels of tissue plasminogen activator and reduced activity and concentration of tissue plasminogen activator inhibitor. The ratio between thrombin antithrombin-III-complexes (TAT) and fibrin degradation products were unchanged, signifying no effect of hormonal intake on the balance between thrombin formation and fibrinolysis. The dynamic balance between coagulation and fibrinolysis was undisturbed during treatment with both hormonal compounds, and findings do not provide evidence for increased risk of thrombosis in normal women.
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PMID:[Hemostatic balance during treatment with the newest contraceptives]. 829 9


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