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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent cohort and case control studies of low-dose combined oral contraceptives (COCs) containing the new generation of progestogens have allowed classification of adverse effects into those which are rare but serious and should be considered risks and those which are more frequent but are less of a threat to health. Low-dose COCs continue to affect coagulation in a complex way, but the risk is less than with the older preparations, and it can be minimized by screening women for a personal or familial history of early or unusual thrombosis and for levels of protein C, S, and antithrombin III. Women with true migraine with focal signs should also avoid using COCs. The relative risk of myocardial infarction (MI) may increase from 4:1 in women with one risk factor (age, smoking, hypertension, hyperlipidemia, and diabetes) to 20:1 with two risk factors and 128:1 with three or more risk factors. In the absence of all risk factors, a recent study indicated that the relative risk of MI with COC use was 1.9 for current and past use. COC use also causes a slight increase in hypertension in most women, especially those who are older or have a family history of hypertension. While the COC can affect carbohydrate and lipid metabolism, the new generation of progestogens has reduced these effects. The COC may accelerate presentation of gallbladder disease in predisposed women. The COC protects against benign breast disease but may increase the risk of breast cancer and cervical cancer slightly. There is a strong link between hepatocellular adenoma and COC use, but the incidence is low. Return to fertility after use has not been a problem. Both estrogenic adverse effects (nausea, dizziness, irritability, weight gain, bloating) and progestogenic adverse effects (vaginal dryness, acne, hirsutism, weight gain, depression, loss of libido) can occur in 50% of women, but these generally disappear after a few months of use. In conclusion, the low-dose, third generation COCs are associated with minimal risks in the absence of other risk factors and have many beneficial effects such as the prevention of ovarian and endometrial cancer; a decrease in pelvic inflammatory disease and ectopic pregnancies; and protection from anemia, primary dysmenorrhea, functional ovarian cysts, and benign breast disease as well as from the morbidity and mortality associated with pregnancy.
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PMID:The combined oral contraceptive. Risks and adverse effects in perspective. 776 40

The evidence of the effects of combined oral contraceptives (COCs) on mortality and morbidity is reviewed. All the 11 case-control studies published since 1980 reported and approximate halving of endometrial cancer risk among COC users. The CASH study showed that the protective effect was apparent after 12 months' use, and users had 40% of the risk of non-users after 2 years' use. A study showed that 5 patterns of self-perceived prolonged, heavy, frequent, irregular, or painful bleeding during menstruation were reported less frequently in COC users than in users of other methods. Benign breast disease is rarer, and functional ovarian cysts are less frequent in COC users. Lower-dose preparations may carry a lower risk of myocardial infarction. Smoking possibly potentiates the risk associated with oral contraceptive (OC) use, and it is a major risk factor for myocardial infarction. The Oxford/FPA study found a 2-3-fold increase in incidence of non-haemorrhagic stroke among current OC users. The epidemiologic data on the current risk of venous thromboembolism in relation to OC use are equivocal. New lower dose COCs have a smaller adverse effect on the lipid profile: they cause a smaller increase in low density lipoprotein cholesterol (LDL) and a variable but smaller decrease in high density lipoprotein cholesterol (HDL). The large CASH study, based on 2088 cases, found a significantly elevated relative risk (2.7) of breast cancer, but only in women who had used the OC for at least 11 years. Of 6 case-control studies of hepatocellular carcinoma and OC use published since 1983, all but one showed a large elevated relative risk of around 4-fold. Delayed return of fertility has been observed in nulliparous women 30 who had 2 years; continuous exposure to COCs, although this may not be associated with low-dose, modern OCs. Malignant melanoma, pituitary adenoma, gallbladder disease, and chronic inflammatory bowel disease have been possibly associated with adverse side effects, but results are so far inconclusive.
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PMID:Combined oral contraceptives: risks and benefits. 832 3

In 1973, McGuire and Chamness (In: O'Malley BW and Means AR (ed) Receptors for Reproductive Hormones, Plenum Press) summarized their work on the estrogen receptor in animal and human breast tumors, and in so doing described a target for therapeutic intervention. At that time there were no clinically useful antiestrogens, but the subsequent development of tamoxifen for breast cancer therapy has revolutionized the approach to treatment. Long-term adjuvant tamoxifen adjuvant therapy (i.e., greater than one year) has proven efficacy to enhance the survival of breast cancer patients. In addition, because there is an associated 40% decrease in contralateral breast cancer during adjuvant tamoxifen therapy and tamoxifen maintains bone density and reduces fatal myocardial infarction, clinical trials to test the worth of tamoxifen as a preventive for breast cancer in high risk women have started in the United States, United Kingdom, and Italy. Initial concerns that long-term tamoxifen causes endometrial cancer have been placed in perspective and analyzed by a review of the literature. Tamoxifen only doubles the normal risk of detecting endometrial cancer (i.e., to 2 per 1,000 tamoxifen-treated women per year), and 80% of these cases are early stage, good prognosis disease. Annual gynecological examinations and education are essential to provide reassurance for patients. The success of tamoxifen has encouraged the development of new antiestrogens to exploit the estrogen receptor as a therapeutic target. Droloxifene and TAT-59 mimic the metabolite 4-hydroxytamoxifen in having a high affinity for the estrogen receptor (Jordan et al, J Endocrinol 75:305, 1977). These drugs appear to have a pharmacological profile similar to tamoxifen. In contrast, the new pure antiestrogens have a distinct mechanism of action and will be valuable either as a first line therapy for advanced breast cancer or as a second line endocrine therapy after the failure of long-term adjuvant tamoxifen therapy. Finally, a new strategy is being developed to exploit the target site specific action of antiestrogens. Raloxifene, an antiestrogen with high affinity for the estrogen receptor but only weak estrogenicity for the uterus, prevents rat mammary tumorigenesis and maintains bone density. The drug is to be evaluated as a treatment for osteoporosis, but may also prevent the development of breast and endometrial cancer in a broad group of treated subjects. The identification of the estrogen receptor as a target for therapeutic opportunities has proved to be extremely beneficial for the control of breast cancer and has the added potential to control osteoporosis and coronary heart disease in women.
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PMID:Third annual William L. McGuire Memorial Lecture. "Studies on the estrogen receptor in breast cancer"--20 years as a target for the treatment and prevention of cancer. 857 10

Some women take an estrogen preparation for as long as several years to ease symptoms of the menopause. Such women appear to have little or no alteration in their risk of endometrial cancer, especially if they are also taking a progestogen, and no alteration in their risk of breast cancer. Similarly, the incidence of fractures is unaffected by relatively short-term hormone use. The risk of ischemic heart disease also is reduced among women who currently take estrogens (with or without a progestogen), but the influence of duration of use on this association is uncertain. Postmenopausal women who take estrogens for an extended period of time (e.g., a decade or more) incur a sharply increased risk of cancer of the endometrium. This is largely abated by use of a progestogen for at least 10 days per month. Such long-term estrogen use, whether accompanied by a progestogen or not, may increase the risk of breast cancer slightly, but this is an area of great controversy, at present unresolved. The incidence of both myocardial infarction and fracture is substantially reduced in long-term users of menopausal hormones.
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PMID:Health consequences of short- and long-term postmenopausal hormone therapy. 869 9

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

Cigarette smoking is an established risk factor for cancer and cardiovascular disease, and is the leading cause of avoidable disease in most industrialized countries. Less well-known are possible beneficial effects, which are briefly considered in this survey. Preliminary data suggest that there may be inverse associations of smoking with uterine fibroids and endometriosis, and protective effects on hypertensive disorders and vomiting of pregnancy are likely. Smoking has consistently been found to be inversely related to the risk of endometrial cancer, but cancers of the breast and colon seem unrelated to smoking. Inverse associations with venous thrombosis and fatality after myocardial infarction are probably not causal, but indications of benefits with regard to recurrent aphthous ulcers, ulcerative colitis, and control of body weight may well reflect a genuine benefit. Evidence is growing that cigarette smoking and nicotine may prevent or ameliorate Parkinson's disease, and could do so in Alzheimer's dementia. A variety of mechanisms for potentially beneficial effects of smoking have been proposed, but three predominate: the 'anti-estrogenic effect' of smoking; alterations in prostaglandin production; and stimulation of nicotinic cholinergic receptors in the central nervous system. Even established inverse associations cannot be used as a rationale for cigarette smoking. These data can be used, however, to clarify mechanisms of disease, and point to productive treatment or preventive options with more narrowly-acting interventions.
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PMID:Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious. 874 97

The estrogen receptor has been successfully targeted with the anti-estrogen tamoxifen to treat all stages of breast cancer. Because tamoxifen is a partial agonist, it exhibits target-site specificity: it acts as an anti-estrogen in the breast to inhibit tumor growth, while exhibiting estrogenic effects on bones and lipid metabolism. Therefore, tamoxifen has the added benefit of maintaining bone density and reducing the risk of myocardial infarction in postmenopausal women. However, undesirable side effects of tamoxifen preclude its use as a hormone replacement therapy for otherwise healthy women. New anti-estrogens are currently being developed that may prevent osteoporosis, breast and endometrial cancer, and reduce the risk of myocardial infarction.
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PMID:Targeted anti-estrogens to treat and prevent diseases in women. 879 91

The main adverse effects of tamoxifen, aspirin, oral contraceptives (OCs) and retinoids used as chemopreventive agents in humans are reviewed and quantified here. With regard to tamoxifen, there are suggestions of some excess risk of liver, and perhaps gastrointestinal, cancers. The public health impact of such associations, if any, is still unclear. Tamoxifen use is associated with endometrial and myometrial hyperplasia. Data from five studies based on 174 cases indicate that the overall relative risk (RR) of endometrial cancer in ever tamoxifen users is 1.73 (95% confidence interval = 1.1-2.6). However, there is a significant difference between the results of American and European studies, so the relationship between tamoxifen and endometrial cancer remains open to debate. The major side-effect of aspirin is gastrointestinal lesions; the risk of these is increased two- to tenfold, depending on the dose. Aspirin is also associated with an increased risk of haemorrhagic stroke, although its protection against other types of stroke and against myocardial infarction leads to a favourable pattern of risk for all cardiovascular conditions. Short-term side-effects of OCs include vascular diseases and a moderately increased risk of breast cancer. The RR of cervical cancer and hepatocellular carcinoma are also increased in OC users, although the public health impact of such associations is small. Toxicity associated with retinoid treatment is rarely serious as most effects observed are reversible on stopping use. Side-effects include changes in the skin and mucous membranes (dry skin, hair loss, dry nose, conjunctivitis), musculoskeletal symptoms, ophthalmological effects, changes in transaminase activity, changes in clinical chemistry markers (increase in serum triglycerides and decrease in high-density lipoproteins) and, rarely, central nervous system effects. A serious toxicological aspect of retinoid treatment is teratogenesis; its use should therefore be avoided in women with childbearing potential, and, in cases of use, conception should be delayed for a long time after stopping treatment. Thus, when considering side-effects of chemoprevention, the major issues of concern are the rare long-term effects (chiefly neoplasms), and the need for more precise overall risk-and cost-benefit assessment, particularly for healthy people.
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PMID:Adverse effects of preventive therapy in humans. 892 25

The failure of follicular development that characterizes the menopause leads to a marked reduction in serum levels of estradiol and progesterone. As a result, the majority of women develop symptoms, including hot flushes, sleep disturbance, and vaginal dryness. Long-term consequences of ovarian insufficiency include genital atrophy, osteoporosis, and increased rates of myocardial infarction. Estradiol replacement (ERT) has proved effective in treating and preventing these problems. ERT has, however, led to increased risk of endometrial carcinoma. Consequently, treatment regimens now include progestins (HRT) to protect women who have a uterus. Progestins act by down-regulation of estradiol receptor activity, which is an advantage for preventing endometrial hyperstimulation, but a potential disadvantage when beneficial effects of estradiol are opposed. Current menopause health care includes assessment, treatment, and follow-up. Signs and symptoms of estradiol deficiency are evaluated during initial history-taking and physical examination. The MENSI (Menopause Symptom Index) has proved an efficient questionnaire for both initial assessment and monitoring of treatment effects. Vaginal cell maturation index (M.I.) can be helpful in determining need for hormonal treatment and for assessing response to treatment. A "therapeutic range" for ERT can be achieved with the availability of a variety of hormone preparations administered in different ways (oral, transdermal, skin gel, implants, etc.), thus avoiding the problems of both inadequate and excessive hormonal doses. This paper will describe a structured approach to the delivery of health care in the menopause.
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PMID:Hormone replacement therapy in the menopause. 916 Feb 17

Toxifen, a nonsteroidal antiestrogen, is currently the most widely used adjuvant therapy for the treatment of breast cancer. Though the efficacy of tamoxifen has been well documented in clinical trials, the certainty over the duration of therapy is less clear. Clinical and laboratory evidence suggests that longer therapy is better; however, whether this means 5 years, 10 years, or indefinite therapy has not been established in clinical trials. Essential to any study of long-term tamoxifen therapy is consideration of its effects not only on breast cancer but also on other estrogen target tissues. The estrogenic effect of tamoxifen that lowers serum lipids results in fewer hospital admissions for heart disease and a reduction in fatal myocardial infarction. Similarly, tamoxifen maintains bone mass that may ultimately result in fewer fractures. The effects of tamoxifen appear to parallel the effects of estrogen, so results from clinical trials of estrogen replacement therapy will provide a useful guide of what to expect with tamoxifen. The negative aspect of the therapy is a modest increase in the incidence of endometrial cancer. However, the incidence of endometrial cancer after stopping either estrogen or tamoxifen remains elevated for at least 5 years after the drug is stopped. Nevertheless, it is important to stress that the overall prognosis remains unaffected. We conclude that it will be difficult to demonstrate survival differences between 5 and 10 years of tamoxifen in clinical trials unless significant tamoxifen-stimulated recurrences occur with continued therapy. The benefits of tamoxifen must be calculated using estimates of the decreased rates of heart disease, contralateral cancers, decreased hospitalizations for fractures, and reduced cancer relapses.
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PMID:Should adjuvant tamoxifen therapy be stopped at 5 years? 916 14


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