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Query: UMLS:C0038454 (stroke)
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Recent data on oral contraceptives (OCs) employing new low-dose formulations appear to indicate that most of the previously reported metabolic effects are minimized, particularly when a product is neigher ovverly estrogenic nor progestational. Evidence suggests that elevated levels of cholesterol and triglycerides in the plasma are correlated with the risk of cardiovascular disease. Epidemiologic students have indicated a correlation between elevation of low denisty lipoprotein (LDL) cholesterol and coronary heart disease, and a correlation between decreases in high density lipoprotein (HDL) cholesterol and arterial disease. Epidemiologic evidence seems to suggest that combination OCs are associated with increased cardiovascular risk, especially risks of venous thrombosis, myocardial infarction, and stroke. There is some debate as to whether OCs themselves are an independent risk factor or whether they increase the effects of other risk factors. Women using combination OCs have been reported to have higher total serum triglyceride and cholesterol concentrations, related primarily to the estrogen dose. While most of the earlier literature associated estrogens with a higher risk of cardiovascular disease, recent studies have increasingly implicated the progestin component. Increasing potencies of progestin have been found to proportionally lower the HDL-cholesterol level. There is a positive association between the estrogen dose and HDL-cholesterol level. Among combination pill users, HDL levels gevverally depend on the relative amounts and potencies of both components. It is generally agreed that there are some high-risk women who should be carefully monitored while using the pill or who should not use it at all. Steroid type and dosage both play a role in affecting carbohydrate metabolism. Ethinyl estradiol (EE), the estrogen component in most OCs, does not seem to have the same biphasic effect on carbohydrate metaolism as most other estrogens. Most of the recent literature suggests that 19-norprogestins alter carbohydrate metabolism in a dose-related manner. The major problems in carbohydrate metabolism have been caused by high dose OCs and the progestin norgestrel. The recent literature confirms the advantages of the new low-dose compounds, with 1 study finding no adverse effects on carbohydrate metabolism and no significant change in plasma insulin levels with a dose of 35 mcg EE and .4-.5 mg norethindrone. The use of OCs in prediabetic and insulin-dependent diabetic women must be weighed against the dangers of pregnancy and the characteristics of the individual patients.
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PMID:Pill formulations and their effect on lipid and carbohydrate metabolism. 648 7

Low dose estrogen tablets, containing less than 50 mcg of ethinyl estradiol, were formulated because of the recognized dose response relationship with the steroid content of the tablet and side effects. These new oral contraceptives (OCs) are as effective as the older high-dose OCs, and available evidence reports fewer side effects. This discussion reviews pharmacology of these new OCs, the mechanism of action, contraindications, side effects, and problems with the low-dose estrogen OC. Ethinyl estradiol is the only estrogen used in the low-dose combination OC. There are several synthetic progestins: norethindrone, norethindrone acetate, norgestrel, levonorgestrel, and ethynodiol diacetate. These progestins have different potencies so the pharmacologic activity cannot be accurately predicted based on the amount present in the tablet. The synthetic steroids in OCs are absorbed in the small intestine, metabolized in the liver, excreted in the bile and feces with a half-life of 24 hours. The low-dose estrogen combination preparation is taken 3 out of every 4 weeks. Its contraceptive effect is primarily a result of hypothalamic mediated gonadotropin suppression with subsequent inhibition of ovulation. Contraindications to taking the low-dose OC are the same as for the higher dose OC: thromboembolic or cardiovascular disease, estrogen dependent neoplasia, markedly impaired liver function, undiagnosed genital bleeding, congenital hyperlipidemia, pregnancy, and women over age 30 who smoke. Relative contraindications include hypertension, diabetes mellitus, migraine headaches, uterine myomas, and epilepsy. The often quoted 2-5-fold increased incidence of thromboembolic disease, myocardial infarction, and stroke is based on large epidemiologic studies involving patients taking the older higher dose OCs. Current data from patients taking the newer low-dose medication demonstrate minimal if any increased incidence of these problems in young women who do not smoke. The low-dose estrogen OCs have minimal effect on lipid levels. Early reports of patients using the low-dose OC have shown little if any increased incidence of hypertension. The low-dose contraceptives have little effect on glucose tolerance, and there is no evidence to show an increased incidence of overt diabetes in OC users. There is no evidence that use of the combination OC causes an increase in cancer of the cervix, uterus, or ovaries. Clinical complaints of nausea, breast discomfort, chloasma, weight changes, and depression are reduced with the low-dose estrogen preparation. Hypomenorrhea while taking the OC occasionally occurs because the lower dose of estrogen is insufficient to stimulate the endometrial growth in face of the predominant progestin-atrophy effect.
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PMID:Oral contraceptives in 1984. 649 Mar 38

The Collaborative Group for the Study of Stroke in Young Women and other similar studies linked oral contraceptives with increased risk of cardiovascular diseases. It is hypothesized that an increased risk for stroke should also be seen among postmenopausal women using estrogens as compared with nonusers. To test this hypothesis, a total of 198 postmenopausal subjects, most of whom were between 50 to 80 years of age, and with a diagnosis of stroke during the period 1972 to 1974, were compared with 396 controls (those who had not had strokes) chosen randomly from the data bank of the Kaiser Foundation Health Plan. The 198 subjects were from the Northern California Kaiser Foundation Hospitals. Both groups were studied for estrogen use and for the associated risk factors of diabetes, hypertension, and coronary artery disease. Of those who had had strokes, 20.7 percent had been taking estrogens, compared to 18.4% in the control group (the difference was insignificant at Chi-Square=0.4396). Relative risk of stroke was calculated by the relative odds method to be 1.16 times as great in estrogen users as nonusers, with 95% confidence limits of 0.75 and 1.77. Estrogen replacement therapy is beneficial for some postmenopausal women. Its risks and benefits must be carefully weighed. This study refutes the association between estrogen use in physiological replacement doses and increased risk of stroke in postmenopausal women.
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PMID:The role of estrogens as a risk factor for stroke in postmenopausal women. 734 44

Estrogen replacement therapy (ERT) has been shown to reduce the risk of cardiovascular disease (CVD) and osteoporosis in postmenopausal women. Studies also indicate a reduced risk of stroke and its consequent mortality among estrogen users, and ERT may also have a role in reducing the risk of Alzheimer's disease and increasing a woman's overall quality of life. On the negative side, some studies show a small duration-related risk of breast cancer with estrogen use and a significant increase in endometrial cancer; the latter is virtually eliminated with the addition of a progestin to the regimen. Although the definitive answer is not yet available, recent epidemiologic data suggest no reduction in protection against CVD and bone fracture with the addition of progestin, which is referred to as hormone replacement therapy, as opposed to using estrogen alone. A woman's potential risks associated with ERT or hormone replacement therapy must be weighed against her lifetime risks of developing CVD, stroke, and bone fracture. The reduction in mortality and morbidity rates with hormone use is generally viewed to be substantial and cost-effective. Health care professionals have an important role in shaping their patients' attitudes. Patients need more information from their physicians about the risks and benefits of estrogen therapy.
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PMID:Benefits and risks of estrogen replacement therapy. 757 95

A women spends about one-third of her life in her postmenopausal years. Some women supplement this period of decreased estrogen production with estrogen replacement therapy (ERT). Many epidemiologic studies have examined the long-term effect of postmenopausal estrogen deprivation and of ERT. Since the 1970s, we have evaluated the risks and benefits of ERT in one population of older women in the California retirement community of Leisure World. ERT is the most effective method for preventing osteoporotic bone loss and fractures in postmenopausal women. In Leisure World, ERT reduced the risk of hip fractures by about 50%. The effect is greatest in longterm users, but may be lost after discontinuation. Postmenopausal osteoporosis affects the bones of the jaws as well as other skeletal bones. Bone loss in the jaws may result in tooth loss. In Leisure World, estrogen users have retained more natural teeth than nonusers. Cardiovascular disease is the leading cause of hospitalization and death in women. In Leisure World, ERT reduced the risk of fatal and nonfatal myocardial infarction, ischemic heart disease, other heart disease, and stroke by 20-40%. The reduction is greatest in long-term and/or current users. ERT is effective in women with and without cardiovascular disease risk factors. One of the most feared aspects of aging is Alzheimer's disease. In Leisure World, women who had used ERT had a reduced risk of Alzheimer's disease. Risk decreased with increasing duration of use. Estrogen use, however, is not without risk. Unopposed estrogen increases risk of endometrial cancer. Risk increases with increasing years of use and remains high after discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The risks and benefits of estrogen replacement therapy: Leisure World. 758 89

Epidemiologic research has correlated current low-dose estrogen oral contraceptives with a low risk of myocardial infarction, stroke, and venous thrombosis or thromboembolism. Nevertheless, misgivings still linger about the effects of low-dose oral contraceptives on the cardiovascular system. Changes in the coagulation system have been linked primarily to the estrogen component; however, the progestin may have an influence on the fibrinolytic system. Oral contraceptives (OCs) containing desogestrel, a new progestin, became commercially available in Europe in 1981. Since that time, more than 30 million women have used the monophasic preparation containing 150 mcg of desogestrel and 30 mcg of ethinyl estradiol. During this widespread clinical use, desogestrel-containing OCs have not been associated with an increase in the risk of thromboembolic disorders. A total of 13 studies from different countries involving different ethnic groups were reviewed concerning the effects of OCs containing novel progestins on coagulation and fibrinolytic variables. The observed changes indicate that a new balance has occurred, increases in both procoagulation and profibrinolysis factors and their inhibitors. With the exception of two studies, all studies were comparative versus a variety of low-dose oral contraceptives. None of the studies observed a notable difference between the desogestrel OC and the comparison OC, and no incidental difference between OCs was confirmed in a subsequent study. This lack of a specific progestin effect confirms an earlier theory that any thrombogenic effect of oral contraceptives is caused by the estrogen component. Desogestrel differs from progestins currently in use in its lower relative androgenicity, which eliminates or reduces adverse effects on lipid and carbohydrate metabolism. The use of the desogestrel-containing OC is associated with minimal changes in the coagulation and fibrinolytic systems. A careful medical and family history rather than the selection of a particular OC combination is an effective means of preventing thromboembolic disorders.
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PMID:The effects on hemostasis of oral contraceptives containing desogestrel. 844 59

A leading patient complaint is headaches which tend to occur more often in women than men. Nonvascular headache is the most common and is caused by tension or muscle contraction. Oral contraceptives (OCs) do not affect nonvascular headaches. They can also be safely used in women who experience common migraines whose symptoms do not become more severe or frequent during OC use. On the other hand, women who have classic migraine (headache accompanied by focal neurologic symptoms) or common migraine with symptoms becoming more severe or frequent during OC use should discontinue OC use. Instead, they should use a barrier method or the IUD. Estradiol treatment appears to be effective in treating menstrual migraine. Since the data are inconclusive about the effect of OCs on young women who have experienced a stroke or transient ischemic attacks, it would be best for them to use a barrier method. Most antiepileptic drugs (phenobarbital, phenytoin, paramethadione, and carbamazepine) cause enzyme induction which may be linked to decreased levels of estrogen and increases in irregular bleeding, thereby increasing the likelihood of an epileptic OC user becoming pregnant. Possible contraceptive failure exposes a developing fetus to the teratogenic properties of the antiepileptic drugs. Thus, physicians should prescribe OCs with 50 mcg of ethinyl estradiol rather than 35 mcg ethinyl estradiol. Epileptic women can also use Depo-Provera, because it is not only effective in preventing pregnancy but reduces seizure frequency. It is important for any contraceptive method chosen for epileptic women to be effective because pregnancy intensifies seizures which in turn can damage the mother and/or fetus and cause neonatal distress.
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PMID:Contraceptive methods for women with neurologic disorders. 851 48

A woman spends about one-third of her life in her postmenopausal years. Some women supplement this period of decreased estrogen production with estrogen replacement therapy (ERT). Since the 1970s, we have evaluated the long-term risks and benefits of ERT in one population of women, the Leisure World retirement community. ERT is the most effective method for preventing osteoporotic bone loss and fractures in postmenopausal women. In Leisure World, ERT reduced the risk of hip fractures about 50 %. The effect is greatest in long-term users but may be lost after discontinuation. Postmenopausal osteoporosis affects the bones of the jaws as well as other skeletal bones. Bone loss in the jaws may result in tooth loss. In Leisure World, estrogen users retain more natural teeth than nonusers. Cardiovascular disease is the leading cause of hospitalization and death in women. In Leisure World, ERT reduced the risk of fatal and nonfatal myocardial infarction, ischemic heart disease, other heart disease, and stroke by 20-40 %. The reduction is greatest in long-term and/or current users. ERT is effective in women with and without cardiovascular disease risk factors. A most feared aspect of aging is Alzheimer's disease. In Leisure World, women who had used ERT had a reduced risk of Alzheimer's disease. Risk both increaseng dose and decreased with increasing duration of use. Estrogen use, however, is not without risk. Unopposed estrogen increases risk of endometrial cancer. Risk increases with increasing years of use and remains high after discontinuation. The most important potential risk of ERT is breast cancer. In Leisure World, women who had used a total accumulated estrogen dose of 1500 mg or more had nearly twice the risk of breast cancer compared with nonusers. Short-term low-dose users showed no substantial increased risk. The Leisure World Study shows risks and benefits of ERT similar to other reports in the literature. For postmenopausal women generally, the benefits of ERT--preventing osteoporotic fractures, reducing heart disease, decreasing mortality, and possibly reducing risk of Alzheimer's disease-out-weigh the risks of endometrial and breast cancers. A woman must be fully informed of the risks and benefits of hormone therapy and play an important role in deciding whether to take hormones and which regimen to use.
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PMID:Estrogen replacement therapy in the elderly. 870 21

Onset of acute atherothrombotic events (acute myocardial infarction, unstable angina, ischemic stroke) exhibit a circadian pattern that parallels the diurnal pattern of endogenous fibrinolytic activity. Hormone replacement therapy in postmenopausal women has been shown to enhance fibrinolytic capacity by lowering plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator inhibitor (tPA) antigen values. We evaluated the impact of 4 weeks of estrogen alone (Premarin 0.625 mg/day) and 2 weeks of estrogen plus progesterone (Provera 2.5 mg/day) on PAI-1 and tPA in 17 postmenopausal women at multiple time points to assess hormone impact on the diurnal pattern of fibrinolytic potential. At baseline, both PAI-1 and tPA exhibited circadian variability. Estrogen alone selectively lowered 8 A.M. PAI-1 (35.8 +/- 7.1 ng/ml at baseline, 19.8 +/- 3.7 ng/ml on estrogen; p = 0.0002 vs baseline). There was no significant change in the noon or 4 P.M. values, and the diurnal pattern was attenuated. The 8 A.M. PAI-1 remained low at 17.1 +/- 3.6 ng/ml (p = 0.0001 vs baseline) with total loss of the circadian rhythm. Estrogen supplementation reduced tPA antigen at all time points, and the diurnal pattern, although blunted, persisted. Addition of progesterone to estrogen did not reverse effects of the estrogen alone phase of either PAI-1 or tPA values. This hormone-associated reduction of PAI-1 was observed despite increased triglycerides, a known inducer of PAI-1 levels. These observations suggest that hormone replacement therapy may protect postmenopausal women from excess early morning acute ischemic events.
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PMID:Effects of hormone replacement therapy on the circadian pattern of atherothrombotic risk factors. 888 58

A review of the recent epidemiologic evidence indicates that use of low-dose combined oral contraceptives (OCs) is not associated with any clinically significant increase in risk of myocardial infarction (MI) or stroke, including for smokers under 35 years of age. Even if the small elevation in risk for these diseases is assumed to be causal, the incidence of both MI and stroke associated with use of OCs containing under 50 mcg of ethinyl estradiol would be only 2 per 100,000 events per year. This risk would be even lower for women under 35 years of age who do not smoke and have no history of hypertension. Two new reports have identified even lower relative risks of MI and stroke among users of OCs containing the progestins desogestrel and gestodene compared with users of second-generation OCs. However, four additional epidemiologic studies have revealed a two-fold increased risk of non-fatal venous thromboembolism for OCs containing desogestrel or gestodene compared to levonorgestrel; the excess risk is about 15 per 100,000 events per year. Until there is a biologic explanation of the greater thromboembolism risk in users of third-generation OCs, this association should not be viewed as causal and no change in OC prescribing practices is warranted for either current or new acceptors. However, smokers over 35 years of age should not use any combination OCs.
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PMID:Estrogen and progestin components of oral contraceptives: relationship to vascular disease. 922 Feb 22


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