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

This review of the research literature on the cardiovascular safety of oral contraceptives (OCs) containing less than 50 mcg of estrogen and second- or third-generation progestins suggests that these formulations are safer than earlier OCs were. Although some recent studies detected an increased risk of venous thromboembolism of 1.5-2.0 in users of OCs containing desogestrel or gestodene compared with second-generation progestins, these studies are marred by detection bias and the tendency for high-risk women to be prescribed third- rather than second-generation OCs. Studies of the association between combined OCs and myocardial infarction have yielded discrepant results; one found an increased risk with second- but not third-generation OCs. Studies on stroke indicate little or no increase in risk in users of modern OCs without other cardiovascular risk factors. Overall, the available research indicates that use of second- or third-generation OCs carries less risk of venous thromboembolism than pregnancy. In addition to the prevention of pregnancy and its attendant risks, low-dose OCs confer additional health benefits such as reductions in the incidence of ovarian and endometrial cancer.
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PMID:Modern oral contraceptives and cardiovascular disease. 932 46

During the past 20 years, the hormonal therapy of choice for the treatment of breast cancer has been the antiestrogen, tamoxifen. The use of tamoxifen has been proved to produce a favorable response and survival advantage in patients whose tumors are classified as estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+). Additionally, tamoxifen is the only drug known to reduce the incidence of contralateral disease. This drug produces relatively few harmful side effects, while exhibiting several beneficial effects such as maintaining bone density and reducing the incidence of myocardial infarction in the postmenopausal woman. However, tumors eventually acquire a tamoxifen-resistant or tamoxifen-stimulated phenotype, resulting in disease recurrence. Several mechanisms have been proposed to account for tamoxifen-resistant breast cancer, in the hope of developing a more effective first-line or perhaps second-line treatment strategy. One popular theory is the occurrence of a mutation in the estrogen receptor, the drug target. A plethora of studies have reported the detection of estrogen receptor mRNA splice variants, and it has been suggested that the accumulation of these variant mRNAs are responsible for the development of tamoxifen-resistant breast cancer. In this review, several questions will be posed to address the suitability of both laboratory and clinical evidence to support this hypothesis. Although there is adequate data generated in the laboratory, there is, as yet, no compelling evidence to suggest that mutation of the estrogen receptor is the molecular mechanism producing tamoxifen-stimulated growth in human breast and endometrial cancer.
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PMID:The role of estrogen receptor mutations in tamoxifen-stimulated breast cancer. 939 47

The reduction in estrogen production that occurs at menopause is associated with several long term sequelae. There is an accelerated decrease in bone mineral density leading to an increased risk of osteoporotic fracture. Furthermore, changes in plasma lipid profiles and other cardiovascular parameters increase the risk of cardiovascular and cerebrovascular pathology. These effects are additional to the menopausal symptoms experienced by many women. The effectiveness of estrogen-based hormone replacement therapy (HRT) is well established in preventing bone mineral loss and also in ameliorating menopausal symptoms, with the addition of progestogen maintaining or possibly enhancing the bone-conserving effects. However, prolonged therapy appears to be necessary to conserve bone mineral density and prevent osteoporotic fracture, particularly in women aged greater than or equal to 75 years, and compliance with long term therapy is likely to be poor. Estrogen favourably alters plasma lipid profiles, improves coronary blood flow and inhibits the central distribution of body fat. Effects on haemostatic mechanisms and coronary vasomotor response to acetylcholine have also been suggested as mechanisms for the beneficial effects of estrogen on ischaemic heart disease. The effects of concomitant progestogens on plasma lipids are variable, and may depend on the type, dosage regimen and duration of therapy. Pharmacoeconomic analyses of HRT have used a variety of risk assumptions. Relative risk rates of osteoporotic fracture and mortality from myocardial infarction are assumed to reduce to 0.5 after greater than 5 years' therapy. Long term HRT is associated with a relative risk of approximately 1.3 for breast cancer, whereas the relative risk of endometrial cancer is 4.0 to 8.0 in women with intact uteri receiving prolonged unopposed estrogen therapy. HRT that includes progestogens is assumed to incur no added risk of endometrial cancer, and this treatment is generally recommended for women with intact uteri. Data concerning the effect of HRT on quality of life are limited and utility values for hip fracture of 0.95 to 0.36 have been assigned, depending on assumptions of disability. Cost-benefit, cost-effectiveness and cost-utility studies evaluating HRT in the prevention of osteoporotic fracture have differed widely in methodology, making comparison of results difficult. HRT appears to be most economically useful in the prevention of fracture if used in women who have undergone hysterectomy, in women with high risk of osteoporotic fracture or ischaemic heart disease, and/or in women with menopausal symptoms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormone replacement therapy: II. A pharmacoeconomic appraisal of its role in the prevention of postmenopausal osteoporosis and ischaemic heart disease. 1014 66

The Polycystic Ovary Disease (PCOD) is one of the most common endocrine disorders in women with a prevalence of 5%. Affected women often consult a gynecologist because of menstrual irregularities, fertility problems or problems of androgen excess. However, PCOD is a metabolic disorder affecting multiple organs. Studies suggest that those women are at risk for developing several complications such as type II diabetes mellitus, hypertension, dyslipidemia and myocardial infarction. The risk to develop endometrial carcinoma is also elevated. To give adequate treatment to women with PCOD, an interdisciplinary approach of gynecologists together with endocrinologists specialized in metabolic and nutritional disorders at the University of Basel is presented. The work-up for diagnosis and assessment of risk factors is outlined. Goal of this interdisciplinary approach is an adequate evaluation of affected patients and their long-term follow-up to test if proposed interventions as weight loss, treatment of hyperinsulinemia, regulation of menstrual cycle and others can avoid long-term sequelae.
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PMID:[Polycystic ovary syndrome--only relevant in reproductive medicine?]. 1040 2

The polycystic ovary syndrome (PCOS) is an extremely common disorder that occurs in 4% to 7% of women of reproductive age. Although PCOS is known to be associated with reproductive morbidity and increased risk for endometrial cancer, diagnosis is especially important because PCOS is now thought to increase metabolic and cardiovascular risks. These risks are strongly linked to insulin resistance and are compounded by the common occurrence of obesity, although insulin resistance and its associated risks are also present in nonobese women with PCOS. Women with PCOS are at increased risk for impaired glucose tolerance, type 2 diabetes mellitus, and hypertension. Cardiovascular disease is believed to be more prevalent in women with PCOS, and it has been estimated that such women also have a significantly increased risk for myocardial infarction. Many lipid abnormalities (most notably low high-density lipoprotein cholesterol levels and elevated triglyceride levels) and impaired fibrinolysis are seen in women with PCOS. Early diagnosis of the syndrome and close long-term follow-up and screening for diabetes and cardiovascular disease are warranted. An opportunity exists for preventive therapy, which should improve the reproductive, metabolic, and cardiovascular risks.
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PMID:The importance of diagnosing the polycystic ovary syndrome. 1085 83

Tamoxifen is a nonsteroidal antiestrogen that has become the frontline endocrine therapy for all stages of breast cancer. The drug is the only single-agent therapy that, when used in an adjuvant fashion, produces a survival advantage in postmenopausal women. Survival is longer when the estrogen receptor content of the primary tumor is higher, although receptor-poor patients still have a survival advantage from adjuvant tamoxifen equivalent to that noted with combination chemotherapy. The added advantages of tamoxifen are a maintenance of bone density and a decrease in fatal myocardial infarction. Although side effects from tamoxifen are few, patients must be examined for preexisting endometrial carcinoma before beginning drug use. Tamoxifen does not prevent the growth of endometrial tumors. Spotting and vaginal bleeding in postmenopausal patients taking tamoxifen should be followed up with a thorough gynecological examination. The incidence rate of endometrial cancer for tamoxifen-treated patients is 2 per 1000 patients per year. More than 80% of detected endometrial tumors are stage 1 disease and can be cured by hysterectomy.
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PMID:Long-term Tamoxifen Therapy for the Treatment of Breast Cancer. 1088 88

Raloxifene belongs to the group of selective estrogen receptor modulators (SERMs). It interacts with both estrogen receptor alpha and beta, but the postreceptor responses differ from those of estrogens. Raloxifene exerts tissue specific responses that differ from estrogens. The drug increases bone mass by 2-3% and inhibits the risk of subsequent vertebral fractures by 30-50%. Raloxifene reduces the risk of breast cancer by 76% after treatment for four years and builds an atrophic endometrium without any bleedings. Furthermore, the risk of endometrial cancer is not increased. The drug exerts positive effects on plasma lipids, but the effects of these changes on subsequent risk of myocardial infarction and cardiovascular death are still unknown. The main side effects are leg cramps, increases in hot flushes and peripheral oedema. Like estrogen, the drug increases the relative risk for venous thrombosis by a factor three.
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PMID:[Raloxifene]. 1096 34

Oral contraceptives are one of the most highly effective forms of contraception and provide many short- and long-term noncontraceptive health benefits. They control menstrual cycle irregularities, such as breakthrough bleeding and amenorrhea, and are effective in treating dysfunctional uterine bleeding. In addition, for decades after oral contraceptive use is discontinued they are associated with substantial decreases in the risk of ovarian cancer (up to 80%) and of endometrial cancer (40%-50%), and nearly eliminate benign functional ovarian cysts. Long-term oral contraceptive use confers protection against benign breast disease and colorectal cancer, may help prevent rheumatoid arthritis, decreases ectopic pregnancy and hospitalizations for pelvic inflammatory disease, and helps preserve bone mineral density to reduce risk of fractures. Large bodies of evidence from extensive research have clarified the perceived association of oral contraceptive use with cardiovascular disease and with breast cancer. Findings indicate that there is no increased risk of myocardial infarction or stroke associated with oral contraceptive use in healthy, nonsmoking, normotensive women. Although there is a 3- to 4-fold increased risk of venous thromboembolism with current oral contraceptive use, the absolute risk is very small and is half that associated with pregnancy. Women of all reproductive ages, including perimenopausal women, can realize many health benefits through oral contraceptive use, including improved health status later in life.
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PMID:Current perspectives on oral contraceptive use. 1152 Nov 17

The authors draw attention to the important role played by menopause in the onset of arterial hypertension, enhanced coronary risk and dyslipidemia, for which a particularly useful association has been found to be estrogens, only if administered by mouth (alone or with progestins), and statins. The authors review numerous studies for or against the use of estrogens as a means of reducing arterial hypertension and the incidence of myocardial ischemia in menopausal women. In order to ensure therapeutic efficacy, replacement estrogen therapy should not be started at not too late an age, but instead as young as possible (the first 5 years after the start of menopause are optimal), namely before levels of endothelial estrogen receptors start to fall. Moreover, therapy should not be continued for more than 5 years in order to avoid the risk of breast cancer and endometrial carcinoma. With regard to myocardial infarction, it is worth noting that women show a higher frequency of silent and atypical infarction leading to a late diagnosis and therefore the arrival in the coronary unit half an hour or an hour later than men. Together with the onset of myocardial infarction at an older age in women compared to men (5-10 years), and the fact that diagnosis is less accurate in women and treatment less sophisticated, this accounts for the higher immediate and medium-term mortality figures in women following myocardial infarction. However, at least in America studies have shown that the less aggressive diagnostic and therapeutic management of myocardial infarction in women compared to men is not sufficient to cause a significant difference in mortality between men and women 30 days after the event. Turning to arrhythmia, it is worth recalling that supraventricular tachycardia with close rapid complexes, caused by return in the atrioventricular node is more frequent in females and in the second lutein or progestin phase of the menstrual cycle, thus demonstrating the protective role of estrogens against the onset of arrhythmia. The authors also point out the frequent association between ischemic ictus and chronic non-valvular atrial fibrillation in women aged over 75 since they present a very high risk (94%) of death by ischemic ictus. On the one hand, the guidelines recommend the use of anticoagulating therapy in these patients, but on the other there is a very high risk of hemorrhage which acts as a major constraint. Lastly, pregnancy is mentioned as a condition that facilitates the onset of arrhythmia; for example, orthodromic supraventricular tachycardia in Wolf Parkinson White and ventricular tachycardia which usually regresses post-partum.
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PMID:[Women and cardiovascular diseases]. 1203 64

The androgen receptor gene (AR) contains a domain which includes a variable number of CAG sequences and alleles with low numbers of CAG repeats show high transactivation activity when complexed with testosterone. The ratio of 2nd and 4th digit length (2D:4D) is negatively correlated with phenotypic effects of testosterone. Low numbers of CAG repeats and low 2D:4D are both associated with high sperm numbers and protection against breast cancer. This suggests that CAG number and 2D:4D are correlated i.e. low CAG number and low 2D:4D indicate high activation of androgen-responsive genes. Findings from AR studies predict that low 2D:4D will be associated with prostate and hepatocellular cancer, urolithiasis, ADHD, ankylosing spondylitis, spontaneous abortion, and polycystic ovaries, while high 2D:4D will be associated with motor neuron diseases and endometrial cancer. Findings from 2D:4D studies predict that short CAG length will be common in autism and Asperger's syndrome, while high numbers of CAG repeats will be found in men who are prone to early myocardial infarction.
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PMID:The ratio of 2nd to 4th digit length: a proxy for transactivation activity of the androgen receptor gene? 1220 64


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