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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in blood pressure were measured at three-monthly intervals over one year in a prospective study of 704 women using an oral contraceptive (OC) containing levonorgestrel 250 ug with ethinyl estradiol 50 ug and 703 women using an intrauterine device (IUD). The study was conducted in 11 centres in seven developing and three developed countries. Women using OC developed systolic blood pressures which were 3.6-5.0 mmHg higher than those using IUDs; their diastolic pressures became 1.9-2.7 mm higher. The OC-induced change was not affected by climate, age, a family history of hypertension, stroke or heart disease or by a history of hypertension in pregnancy. The life-table rate of hypertension (BP 140/90 or more) in the first year of OC treatment was 0.6 +/- 0.4 in the developing countries and 1.1 +/- 0.8 in the developed ones, per 100 woman-years of use. The vasopressor response to OC varied widely between centres but was not obviously related to the economic development of the country.
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PMID:The WHO multicentre trial of the vasopressor effects of combined oral contraceptives: 1. Comparisons with IUD. Task Force on Oral Contraceptives. WHO Special Programme of Research, Development and Research Training in Human Reproduction. 250 94

The objectives of this article on epidemiological studies of health risks from oral contraceptives (OCs) is to review major studies of the association between OCs and circulatory disease and cancer. It is also to emphasize methodologic limitations of the existing data, and to identify unresolved and important questions. A brief discourse on the nature and imputation of relative risk is provided. Cardiovascular diseases covered include ischemic heart disease, stroke, and thromboembolism. Current studies on low dose pills from 3 large US populations reveal that there is no impact of death from use of OCs. A Great Britain and the Walnut Creek study from the US found a slight but not statistically significant increase in ischemic heart disease. These studies also found a statistically significant 3-fold increase in stroke among OC users and, from another study, a 2-fold increase. These studies were based on high levels of ethinyl estradiol where the risk becomes apparent. The risk for idiopathic venous thromboembolism was 3- 8 fold for current OC users. The accuracy of these findings is questioned when the data reflect such heterogeneity. Cancer is differentiated as breast cancer, endometrial cancer, ovarian cancer, cervical cancer, malignant melanoma, and hepatocellular adenoma. For breast cancer, both case control studies as well as cohort studies found no increase in breast cancer. Future additional research will continue to explore unanswered questions about this association. Beneficial effects of OCs occur for endometrial cancer for as long as 15 years after taking the pill. Only 1 year's use resulted in a 50% reduction in risk of endometrial cancer regardless of pill dose and particularly for nulliparous women, who have an increased risk. The longer duration of use of the OCs results in a protective effect against ovarian cancer, i.e., 5 years of use yields as relative risk of below 0.5 and the results of a protective effect can be seen as early as 3 months after pill use. There is about 40% protection against ovarian cancer even with low dose pills; the effect lasts 15 years after cessation of OC use. Cervical cancer studies have shown mixed results. The human papilloma viruses 16 and 18 have been shown to be related to cervical cancer but further research is needed to identify the association with OCs. Data are inconclusive but lean in the direction of no association with malignant melanoma. Hepatocellular adenoma has not been identified in large vital statistics studies, although several small studies have suggested an increased risk. It has been shown by Fortney et al. that with a 50% increase in cervical cancer risk and a 3-4 fold increase in cardiovascular disease risk that OC use for 5 years before the age of 30 years adds 4 days to a health women's life.
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PMID:Results of oral contraceptive epidemiologic studies regarding neoplastic and cardiovascular effects. 257 54

Health care practitioners are often faced with the dilemma of whether or not to provide oral contraceptives (OCs) to women who have certain chronic medical conditions. Oral contraceptive use among gestational diabetics who use OCs may be at increased risk for developing insulin- dependent diabetes. It appears that progestins are primarily responsible because they decrease the number of insulin receptors on cell membranes. Norgestrel has a more marked effect on carbohydrate metabolism than norethindrone. Estrogen may also play a role by slowing the uptake of glucose. Findings of available studies show that progestin only OCs, combined, low-dose OCs (35 mcg of ethinyl estradiol), or preparations with norethindrone are relatively safe for gestational diabetics. In mitral valve prolapse (MVP) abnormal hemodynamics at the prolapsed valve may promote formation of thrombi and lead to cerebrovascular accidents (CVAs). Oral contraceptives are also known to increase the incidence of thrombi, especially in the lower extremities. A 1986 study of 11 OC users who had had CVAS found that a specific subject of women with MVP are at risk for CVA, perhaps due to persistent clotting abnormalities, however most could safely use a combined, low-dose pill unless headaches, smoking, and MVP symptoms. Oral contraceptive use has usually been avoided in women with sickle cell disease. The major concern has been the possibility of an additive or synergistic effect of OCs on the blood-clotting mechanism. However sickle cell disease is a relative contraindication. Several studies showed that OC use, even up to 54 months, did not increase sickle cell crises, and only 5 cases of thromboses have been reported. The increase of fetal and maternal mortality, however, is a definite risk, therefore a similar low-dose pill may be safe for women with the sickle cell trait.
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PMID:Oral contraceptive use in women with chronic medical conditions. 267 89

The benefits and risks of both oral contraceptives and estrogen replacement therapy (ERT) are evaluated by summarizing briefly the results of the most evidential studies on breast, ovarian, endometrial, and hepatobiliary cancer, heart attack, stroke and venous thromboembolism. The methods used to estimate risk ratios, prospective random-allocation, double-blind trials, and retrospective case- controlled studies, are explained briefly. The ERT used today resemble sequential oral contraceptives, except that only 10-20 mcg ethinyl estradiol is taken for 25 days, and progestins are used on the last 10 days. Breast cancer risk is not different in pill users from nonusers, based on the U.K. General PRactitioner, Oxford Family Planning, Harvard nurses or U.S. SEER National Cancer Institute studies. Studies on ERT and breast cancer are mixed, but only injected estrogens raised the risks. Ovarian cancer is prevented by pill use in proportion to length of use. No studies were reported for ERT. The risk of hepatic cancer is 3.8 to 7.8 higher in pill users, but the number of cases is so rare that this should not affect prescriptions. Neither pill nor ERT raise the risk of myocardial infarction, and after premature surgical menopause, ERT lowers the risk. Based on studies done in the 1970s, oral contraceptives raise the risk of thrombotic stroke while women are taking them, from 10-13/100,000 to 41/100,000. ERT has no clear association with stroke. Similarly, orals increase the risk of venous thromboembolism, 8-fold in the Oxford Family Planning study published in 1986, although the absolute numbers are very small. ERT had no effects no risk of thromboembolism according to the lipid Research, Framingham and Nachtigall studies.
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PMID:The risks of oral contraceptives and estrogen replacement therapy. 268 99

This third paper from the Persantine Aspirin Trial examines the data to identify risk factors for stroke in persons with a history of carotid territory transient ischemic attacks (TIAs) Fifteen centers in the United States and Canada participated, and 890 subjects were admitted and randomly allocated to either aspirin plus placebo or aspirin plus dipyridamole (Persantine). Persons with the following characteristics were in greater jeopardy for stroke, retinal infarction, or death: older age, history of heart disease, history of peripheral vascular disease, and persisting neurologic deficit from a recent event. Elevated diastolic blood pressure, diabetes, use of estrogen, and smoking were not found to be risk factors. Elevated systolic blood pressure was a risk factor primarily in subjects with a history of heart disease. Estrogen use may actually have had a protective effect for women. This cannot be considered as a report of the natural history of TIA patients; it does identify risk factors in a specific cohort of subjects under treatment.
Stroke
PMID:Persantine aspirin trial in cerebral ischemia--Part III: Risk factors for stroke. The American-Canadian Co-Operative Study Group. 286 49

Estrogen-progestogen oral contraceptives (OCs) have been shown in numerous studies to increase the risk of venous thromboembolic disease, myocardial infarction, and thrombotic stroke. Until recently, it has been assumed that the increased risk of vascular disease was attributable to the estrogen component of the OC. However, available evidence suggests that venous thromboembolic complications are determined by the estrogen component, whereas arterial complications may be due to both the estrogenic and progestogenic components. The authors investigated the comparative effect of different low-dose combined OCs on the hemostatic system. The effects of ethinyl estradiol on coagulation fibrinolysis and platelet function were found to be dose-related: 50 mcg of ethinyl estradiol produced significantly greater changes than 30 mcg, and the effects of 30 mcg ethinyl estradiol were modified by the progestogen used. Further studies compared 50 mcg and 30 mcg estrogen contraceptives and a triphasic formulation containing levonorgestrel. Again, changes in coagulation activity and fibrinolysis were related to the dose of estrogen and progestogen. The absence of significant changes in antithrombin III with monophasic and triphasic levonorgestrel suggests that levonorgestrel counteracts the action of estrogen in depressing this coagulation inhibitor. The fewest changes in coagulation factors and inhibitors occurred among women taking low-dose estrogen combined with levonorgestrel, indicating that progestogen used in combination modifies the estrogenic effects on the coagulation system. Current research is aimed at finding estrogen-progestogen combinations that produce fewer changes in the hemostatic system and in other metabolic processes. The combination of low-dose ethinyl estradiol with levonorgestrel in a triphasic preparation should reduce the risk of vascular complications and contribute to the safety of OCs.
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PMID:Oral contraceptives and blood coagulation. 294 71

In Europe and North America, estrogen/progestogen oral contraception has been associated with an increase in venous thromboembolism, myocardial infarction, and stroke. These hazards are found mainly in smokers and in women over the age of 35. Venous thromboembolism appears to correlate with the estrogen dosage, and the arterial complications with both the estrogen and progestogen components. Blood coagulation and vascular thrombosis are intimately related. Estrogen/progestogen oral contraception affects blood clotting by increasing plasma fibrinogen and the activity of coagulation factors, especially factors VII and X; antithrombin III, the inhibitor of coagulation, is usually decreased. Platelet activity is also enhanced with acceleration of aggregation. These changes create a state of hypercoagulability that, to a large extent, appears to be counterbalanced by increased fibrinolytic activity. Studies of the oral contraceptives in current use show that the coagulation effects depend on the dosage of estrogen and the type of progestogen used in combination. Current research is aimed at finding the estrogen/progestogen formulations that induce the least changes in the coagulation system and other physiologic processes. In this respect, the new low-dose formulations are a major step forward and should reduce the risk of vascular thrombotic complications.
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PMID:Coagulation effects of oral contraception. 296 Feb 41

The effects of oral contraceptives and estrogen replacement drugs on blood lipids that affect cardiovascular disease (atherogenic effects) are reviewed by comparing their androgenicity and progestin potency. Although early oral contraceptives with high doses of estrogen were indicted for increasing risk of thromboembolic disorders and heart attacks, today's pills low in estrogen still bear the same risk for cardiovascular events. A brief explanation of the lipoproteins is presented, emphasizing the importance of High Density Lipoprotein (HDL) in protecting against heart disease and stroke. Menstruating women have naturally high HDL. The estrogen in oral contraceptives and postmenopausal estrogen replacements increases HDL as much as 30%, while decreasing LDL, the component carrying most of the cholesterol. It seems that the progestin in oral contraceptives will lower HDL, and studies show that this action is related to androgenicity and dose of the progestin. Progestins such as levonorgestrel and norgestrel are more androgenic, while norethynodrel, ethynodiol diacetate and norethindrone are less so. When used in combination with estrogens, progestins are less androgenic, but when used alone, the androgenic and atherogenic effects dominate. The lower the estrogen dose in the combination, say around 20-35 mcg ethinyl estradiol, the more atherogenic the progestin. These actions are confirmed theoretically by measurements of sex hormone binding globulin, a blood protein that reflects estrogen activity, as well as by epidemiologic studies in Sweden and Great Britain, where rates of heart attack and stroke in pill users remain as high as they were when pills contained high doses of estrogen.
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PMID:Low-dose oral contraceptives: progestin potency, androgenicity, and atherogenic potential. 353 47

Three studies directly evaluated the effects of oral contraceptive (OC) use on migraine headache frequency. The Walnut Creek Study in 1980 was unable to demonstrate a higher frequency of migraine headache in OC users discharged from the hospital as compared with nonusers. Another study in 1978 evaluated the effect of 0.5 mg of norgestrel and 50 mcg of ethinyl estradiol (Ovral) on 40 migraine sufferers. 20 patients received this preparation for the first 2 months of the study, the other 20 did not. 29 patients experienced worsening of their headaches with OC use. However, one-third of the patients did note improvement in their headaches. A third study in 1976 of women suffering from migraine suggested that about one-third of women noted worsening of their headaches while taking OCs. The risks of cerebrovascular accident (CVA) include advancing age, smoking, and the use of high-dose pills. Increase in blood pressure, platelet aggregatability, and cholesterol deposition are the three known mechanisms of the risk of stroke. No blind study of the subject has even been made, and a significant minority of OC users reported improvements in their migraine headaches. Circumstantial evidence suggests that there is an increased risk of stroke in OC users, although these case control studies differed with regard to the degree of relative risk. Two of three cohort studies were unable to demonstrate the increased risk of CVA among these women. The absolute risk of thrombotic stroke remains small for OC users, and the absolute risk is probably very small even for those taking OCs. However, the risk of hemorrhagic stroke may increase fivefold in those smoking. For nonsmokers, OC use is probably safer in all age groups than no contraception. A 1977 study showed that 40-44 year old nonsmokers taking OCs had an estimated death rate of 7/100,000. In contrast, those who used no method of contraception had a higher mortality rate of 23/100,000.
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PMID:Relationship of migraine headache and stroke to oral contraceptive use. 354 Feb 97

This paper presents a state-of-the-art review of oral contraceptives (OCs), termed one of the epochal developments of modern times. OCs have had both direct and indirect influences on moral, social, and cultural values and on the interaction of population resources and the environment. In recent years there has been a trend away from OC use because of increased mortality rates, especially in women over 35 years of age and smokers. However, epidemiologic studies have indicated that the incidence of death from cardiovascular disease, thromboembolic disease, and stroke was greatly reduced when newer preparations with lower steroidal doses became available. The reduction of the estrogen content from 150 mcg of ethinyl estradiol-3-methylether to 30-35 mcg of ethinyl estradiol and of the progestin component from 10 mg of norethindrone to 1 mg or less has not interefered with effective conception control. The progestin component of the pill was linked to high blood pressure, lipid changes, and cardiovascular changes with an unfavorable impact on arterial disease. Although many insist that the question of whether OCs cause or predispose to cardiovascular problems cannot be answered at this time, the potential risks involved in OC use are generally regarded to be outweighed by the benefits. Reductions in OC dosages have also reduced the incidence of galactorrhea, amenorrhea, and on-pill amenorrhea. New triphasic formulations that more closely imitate the hormonal fluctuations of the menstrual cycle are considered to hold much promise in terms of safety and effectiveness.
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PMID:Oral contraceptives: the state of the art. 391 70


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