Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mechanism of action, indications, side effects and contraindications of oral contraceptive agents (OCA) are reviewed. OCA can be divided into two groups: consecutive and combined agents. Combined OCA contain both estrogens and gestagens and are taken for 3 weeks, while consecutive OCA contain only estrogens and are taken for 2 weeks followed by 1 week of combined OCA until the onset of menstruation. Biological activity of synthetic gestagens is estimated by a dosage which results in a delay of menstruation by 2 weeks. Gestagens norethindrone and norethynodrel were shown to be equally effective, while ethinodiol diacetate and norgestrel were 15-30 times more effective. Estrogen component of OCA is represented by ethinyl estradiol or mestranol. Combined OCA are more effective than consecutive OCA; probability of undesirable pregnancy during administration of combined OCA does not exceed 0.2%. The most frequent side-effects of OCA include nausea, headache, uterine hemorrhage, and changes in libido. OCA can affect the endocrine and reproductive systems. Major endocrine effects of OCA include changes in the cortisol metabolism in the adrenal glands, increase in the level of thyroid-binding globulin in the thyroid gland, changes in the glucose metabolism in the pancreas, inhibition of the luteinizing hormone releasing hormone in the hypothalamus with simultaneous decrease in the production of pituitary gonadotropins and inhibition of the ovulation. The most serious side-effects of OCA include cholelithiasis, thrombophlebitis, thromboembolism, liver adenoma, and myocardial infarction. Absolute contraindications to the use of OCA include hypertension, hyperlipidemia, breast or endometrial cancer, pregnancy, cardio-vascular diseases, liver diseases, and kidney insufficiency.
 ...
PMID:[Principles of the use of oral contraceptive preparations]. 307 80

Adverse and beneficial effects, especially with regard to mortality rates, of oral contraceptives (OC) are reviewed. In 1980 approximately 80 million women used OCs worldwide. OCs were first marketed in the United States in the 1960's, but by the 1980's low-dose combination pills with less estrogen and progesterone content became widespread along with the minipill, injectable preparations depo- medroxyprogesterone DMPA, and norethindrone containing capsules. Relative disease risk estimates are based on cohort studies and case- control studies. The Royal College of General Practitioners RCGP Oral Contraceptive Study of 1974 involved 46,000 women aged over 15 (50% were OC users, 50% were nonusers) the Oxford Family Planning Association Contraceptive Study of 1976 recruited 17,032 women aged 25-39, 56% of whom used OCs, and the Walnut Creek Contraceptive Drug Study of 1981 studied 16,638 women aged 18-54 of whom 28% were OC users and 33% were former users. A somewhat elevated mortality among ever-users of OCs in the order of 20% seems to be indicated by these studies mostly attributable to diseases of the circulatory system. Current OC use is also a risk factor in thrombotic stroke of the order of 4 or 5, but former use of OCs lowers the risk to 2. The effect of OC dose and formulation, duration of use, and predisposing factors on hemorrhagic and thrombotic stroke appears to be inconclusive with varying data from different studies. There is evidence for some increase in ischemic heart disease among current OC users, and also a 2-fold increase of myocardial infarction (MI) when smoking, serum cholesterol, and hypertension is taken into account, moreover higher estrogen dosage also contributes to a higher incidence of MI. There is also a 5-fold increase of venous thromboembolism among OC users induced by duration of use and estrogen potency, as OCs seem to promote atherogenesis, although the roles of progesterone and estrogen are conflicting. combination pills reduce the rate of endometrial cancer, provided protection against ovarian cancer, and do not seem to increase breast cancer incidence, although the relative risk of cervical cancer is elevated. Mortality risks with older OCs outweigh the benefits.
 ...
PMID:On the epidemiology of oral contraceptives and disease. 331 96

Reduced estrogen content has significantly decreased the risks of oral contraceptive (OC) use. However, the systemic effects of OCs, but it is unclear if this change is physiologically significant. Estrogen-mediated inhibition of cortisol levels may contribute to the impairment of glucose tolerance by OCs. Women at high risk for diabetes, older than 35, obese, with family history of diabetes, or who have had glucose intolerance during previous pregnancies should either not take OCs or take pregestin-only pills. OCs raise plasma triglyceride levels 30-50 mg per dl in users of all ages. High density lipoprotein (HDL) cholesterol is also affected, and cholesterol and triglyceride levelshould be measured before and during OC use. The risk of hepatic adenoma rises with duration of OC use; however, most adenomas diagnosed before hemorrhage have regressed with discontinuation of the contraceptive regimen. The most significant adverse effects of OC use involve the arterial and venous vascular systems. OCs appear to raise the blood pressure in nearly all women. Change in systolic pressure is consistently greater than in diastolic, suggestingthat the primary hypertensive effect of OCs is on blood volume and cardiac output. Accumulated data indicate that if OCs are not used by women older than 35 or by women who smoke or who are hypertensive, then risk of subarachnoid hemorrhage or other cerebrovascular complication is very small. The relative risk of myocardial infarction in OC users has been from 0-6 times greater than in nonusers; this may depend on other confounding risk factors. Reduction in estrogen content of OCs decreases risk accordingly. The preponderance of evidence indicates that prolonged use of OCs does not increase risk of breast disease or ovarian and endometrial cancer, and, in fact, may protect users from malignant lesions by suppressing gonadotropins and ovulation.
 ...
PMID:Systemic effects of oral contraceptives. 608 41

Treatment with oestrogens in the perimenopause can regulate dysfunctional uterine bleeding and positively influence unpleasant subjective feelings such as sweating, dizziness, nervousness and lack or incapability of concentration. Oestrogens are especially successful in reactive depression and in the therapy of insomnia. Their positive effect on atrophic changes of the genitalia and in combating urge incontinence is also of therapeutic importance. Of particular socio-medical importance is their beneficial effect on postmenopausal osteoporosis. Side effects like weight gain, increase in blood pressure or changes in coagulation parameters are not observed during therapy with natural oestrogens in the usual doses. The incidence of thrombosis, embolism and myocardial infarction is not increased when oestrogens are given in the perimenopause. The controversy with respect to an increased incidence of endometrial carcinoma after long-term therapy with oestrogens may be based on an incorrect mode of administration as used on the Anglo-American scene. Excess dosage, continuous instead of intermittent therapy, lack of addition of progestational agents and a neglect of contraindications and risk factors may have led to the 3- to 8-fold increased incidence of endometrial carcinoma after oestrogen therapy in the studies from these areas.
 ...
PMID:[Advances and risks in estrogen therapy in the perimenopause]. 665 19

The use of estrogen replacement therapy in postmenopausal women is under close scrutiny. The indications and side effects of replacement therapy are reviewed, and recommendations regarding its use are made. Hot flashes, atrophy of the vaginal epithelium, and prevention of osteoporosis have been established as indications for estrogen replacement therapy. Prevention of cardiovascular disease, aging changes of skin, and the occurrence of mental illness have also been suggested as indications, but beneficial effects of estrogen replacement therapy for these problems have not been clearly established. Studies have shown that side effects of estrogen replacement therapy include endometrial cancer, hypertension, gallbladder disease, and angina pectoris. Breast cancer may also be a risk factor, but a consensus of opinion has not been established. Pulmonary embolism, cerebral vascular accident, or myocardial infarction has not been associated with estrogen replacement therapy. The use of progesterone with estrogen replacement therapy has been shown to reduce the occurrence rate of endometrial carcinoma, but it does not prevent all the actions of estrogen. Oral administration of estrogen is the preferred route despite misgivings about portal absorption and liver metabolism. Further studies must examine this question. Various agents have been shown to be effective in treating some climacteric symptoms. These include progesterone for hot flashes and calcium for the prevention of osteoporosis. Other agents may also be effective but have not been tested critically.
 ...
PMID:Estrogen replacement therapy. 702 79

The present level of understanding of the known risks of oral contraceptive (OC) use are summarized. The findings of many investigations in the late 1960s and early 1970s may no longer be totally appropriate because OCs available then had higher dosages than today. Also, early studies enrolled predominantly women in their 20s, who are now almost all more than 35 years old. Thus, the risks observed in these studies may not be applicable to younger women using OCs today. Another consideration has been underscored by the results of the Walnut Creek Study. Behavioral characteristics such as smoking, drinking, and sexual activity are factors which can strongly confound risks of OC use and must be considered when assessing current and future investigations. Many studies have clearly shown that the most serious life threatening danger associated with OC use is that of cardiovascular complications arising from the interaction of OC use and smoking. The increased risks attributable to smoking while using OCs account for a substantial number of the deaths recorded. The Walnut Creek Study showed a somewhat different outcome. Its data suggest no significant risk of myocardial infarction (MI), ischemic heart disease, cerebral thrombosis, or ischemic cerebrovascular disease associated with OC use, but there were nonsignificant increases noted in some cardiovascular diseases which appeared to be explained by a synergism between current use and heavy smoking. Age also has a strong influence on risk for cardiovascular disease. The results of earlier studies seem to indicate that OC use is associated with a risk of subarachnoid hemorrhage. The Walnut Creek Study also noted an increased risk of subarachnoid hemorrhage associated with OC use and found that risk increased with use. Several studies have shown that the incidence of venous thrombosis seems dependent on the dosage of the OC used. An overwhelming majority of studies on the carcinogenicity of OCs have found no increased incidence of cancer of the ovaries, uterus, or breast among users. In regard to both ovaries and endometrium, there is some evidence that OCs may be protective. Several studies have concluded that OC users have a slightly increased risk of developing malignant melanoma. The results of the Oxford/Family Planning Study show that although previous use of OC by nulliparous women may delay future childbearing by several months, it does not impair longterm potential for pregnancy. No increase in risk of clinically apparent diabetes mellitus has been reported in users. In addition to their possible protection against ovarian and endometrial cancer, OCs may reduce the risk of at least 5 other diseases: benign breast disease; deficiency anemia; arthritis, pelvic inflammatory disease; and ovarian cysts.
 ...
PMID:The pill: an evaluation of recent studies. 704 36

Several examples of the use of vital statistics in drug epidemiology are described. The death rates for asthma remained stable from about 1860-1960 in the UK, about 0.5/100,000. In 1961 the rates began to rise, and after 1967 they declined; in the 1970s the rates almost approached pre-epidemic levels. The rates were found to vary with the use of isoproterenol-containing nebulizers. Investigations into the relationship between thromboembolism pulmonary embolism, and myocardial infarction and oral contraceptive (OC) usage showed an increase in death rates beginning after the introduction of OCs in 1960-61 in women at risk. Subacute myelo-optic neuropathy was an unexplained disease until Japanese investigators linked its occurrence to ingestion of the halogenated hydroxyquinoline drugs used to treat nonspecific gastroenteritis; seasonal outbreaks of the disease were linked to seasonal gastroenteritis. Animal experiments conclusively linked the drug to the disease. A Swedish report implicated the antihypertensive drug methyldopa as a possible cause of cancer of the biliary ducts. Links between thalidomide and phocomelia, saccharin or cyclamates and bladder cancer, diethylstilbestrol and vaginal cancer, and estrogens and endometrial cancer are discussed. Drug-monitoring systems, the collection of vital statistics and observations by clinicians all contribute to understanding drug-induced disease. Changes in disease incidence or emergency of new syndromes in areas where certain drugs are heavily used should be compared to areas where they are seldom used.
 ...
PMID:The use of vital and morbidity statistics for the detection of adverse drug reactions and for monitoring of drug safety. 716 6

During the 20 years since the oral contraceptive was introduced, it has been used by some 150 million women around the world, and is perhaps the most carefully monitored medication in history. This vast body of research shows that for the overwhelming majority of healthy women under 30, the benefits of the pill continue to outweigh the risks. The most serious life threatening risks are those involving the cardiovascular system: heart attack, stroke, and throboembolism. However, deaths from these causes would be reduced by 1/2 if women using the pill did not smoke; further reductions would result if women with high blood pressure, high chloresterol levels and diabetes millitus did not use the pill. There is no evidence thus far to justify fears that the pill might be associated with an increased risk of cancer. Most studies show that not only is there no association between pill use and cancer of the ovaries, uterus and breast, but pill use may protect against ovarian and endometrial cancer. Women taking the pill are 1/4 as likely to develop benign breast lumps as nonusers, 1/14 as likely to develop ovarian cysts, 2/3 as likely to develop iron deficiency anemia, and 1/2 as likely to develop rheumatoid arthritis -- all relatively common conditions. In addition, pelvic inflammatory disease, a major cause of infertility, appears to occur only 1/2 as often among pill users as among nonusers. The risk to life among pill users younger than 30 who do not smoke is very small (virtually the same as that of users of the IUD, diaphragm, or condom) and is much lower than the risk of birth-related deaths among women who use no birth control.
 ...
PMID:The pill at 20: an assessment. 720 90

Among the many sources of bias that can affect the results of case-control research, protopathic bias occurs when a pharmaceutical agent is inadvertently prescribed for an early manifestation of a disease that has not yet been diagnostically detected. In a case-control study of estrogens and endometrial cancer, approximately 10 per cent of the patients exposed to estrogens specifically stated that oral estrogens had been prescribed by their physician to treat an episode of uterine bleeding. This result was consistent with another study in which seven of 23 estrogen users were given the medication for the treatment of uterine bleeding before the diagnosis of cancer was made. Protopathic bias, which may account for much of the allegedly protective effect of oral contraceptives on the development of benign breast disease, can also occur in studies of aspirin and myocardial infarction, sex steroids and birth defects, and bronchodilators and death from asthma. This empiric demonstration of protopathic bias helps to indicate the need for careful precautions against its effects.
 ...
PMID:The problem of "protopathic bias" in case-control studies. 735 96

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)
 ...
PMID:The risks and benefits of estrogen replacement therapy: Leisure World. 758 89


<< Previous 1 2 3 4 5 6 Next >>