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

Women who self-select to take postmenopausal hormones have lower risks of coronary heart disease, their leading cause of mortality. Women and their primary health care providers must weigh this and other clear (osteoporosis), and possible (stroke, colon cancer, and Alzheimer's disease) benefits against clear (endometrial cancer) and possible (breast cancer) risks. Because all existing data derive only from observational studies, reliable information on the balance of risks and benefits must await the results of the Women's Health Initiative, a large-scale, randomized clinical trial.
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PMID:Postmenopausal hormones and coronary heart disease. 887 56

Obesity is associated with the development of some of the most prevalent diseases of modern society. The greatest risk is for diabetes mellitus where a body mass index above 35 kg/m2 increases the risk by 93-fold in women and by 42-fold in men. The risk of coronary heart disease is increased 86% by a 20% rise in weight in males, whereas in obese women the risk is increased 3.6-fold. Elevation of blood pressure, hyperlipidaemia and altered haemostatic factors are implicated in this high risk from coronary heart disease. Gallbladder disease is increased 2.7-fold with an enhanced cancer risk especially for colorectal cancer in males and cancer of the endometrium and biliary passages in females. Endocrine changes are associated with metabolic diseases and infertility, and respiratory problems result in sleep apnoea, hypoventilation, arrhythmias and eventual cardiac failure. Obesity is not a social stigma but an actual disease with a major genetic component to its aetiology and a financial cost estimated at $69 billion for the USA alone.
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PMID:Obesity as a disease. 924 38

Obesity has consistently been demonstrated to have a detrimental effect upon the female reproductive system. This review explores the common association of obesity with polycystic ovary syndrome (PCOS), the effect of obesity on the clinical and endocrinological parameters, and the role of insulin resistance in the expression of this disorder. An improvement in menstrual function, a decrease in the clinical androgenic profile, and significant increase in spontaneous pregnancy rates have been reported following weight loss. Obesity is associated with poor pregnancy outcome and miscarriage in both women with PCOS, and in those with normal ovarian morphology. The optimal weight gain during pregnancy remains controversial, but obesity is a risk factor for both maternal and fetal complications, and dietary advice should be offered on an individual basis according to the pre-pregnancy BMI. Weight gain at the time of menopause is common, and dietary advice is paramount as obesity is an independent risk factor for thrombosis, coronary heart disease (CHD), and breast and endometrial cancer. Effective nutritional counselling should be offered at all stages of the female reproductive lifecycle.
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PMID:Obesity and female reproductive function. 924 40

In recent years, reports of favourable effects of estrogen therapy on cardiovascular morbidity and mortality have led to enthusiasm for widespread use of estrogens by postmenopausal women. Guidelines for estrogen therapy issued by the American College of Physicians include the statement "Women who have coronary heart disease are likely to benefit from hormone therapy". What evidence support this recommendation? More than 30 observation studies have examined the effect of estrogen replacement therapy on cardiovascular event and all cause mortality. In addition there have been 13 case controlled studies. The majority showed lower morbidity and mortality from coronary heart disease among users of postmenopausal estrogens than among non-users. Recently, 2 meta-analyses estimated the reduction in coronary heart disease associated with estrogen use to be in the range of 35 to 44%, respectively. All of these observational studies share a fatal flaw: Women who take estrogens are different from women who do not. Some differences have been measured, others have not. Women who take estrogens are on average better educated, healthier, have higher incomes and have better access to health care. These difference rather than the estrogens may account for much of the lower risk of heart disease. At this time we cannot tell from these observational studies what the real benefit of estrogens on coronary heart disease might be. Estrogen replacement therapy is not without risk. Estrogens increase the risk of endometrial carcinoma approximately 6-fold, an effect that is eliminated by the addition of progestins. Controversy continues over whether estrogen replacement increases the risk of breast cancer. A number of prospective randomized studies are now under way that will establish whether estrogen replacement therapy definitely reduces the risk of cardiovascular disease in women with and without coronary lesions and whether it increases the risk of breast cancer. Until the results of these trials are available claims on the definite usefulness of hormone supplementation to prevent coronary heart disease in postmenopausal women remain premature. In the light of the probable usefulness estrogen replacement therapy for the prevention of cardiovascular events should be recommended for women with increased risk for or definitively proven coronary heart disease.
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PMID:[Estrogens for prevention of coronary heart disease?]. 930 98

Cardiovascular disease is the leading cause of death in women of postmenopausal age. Data from observational studies suggest that the risk of coronary heart disease in postmenopausal women can be reduced by 30-50% by estrogen replacement therapy. The protective effect of estrogen is multifactorial, affecting lipids, carbohydrate metabolism, hemostasis, body-fat distribution and blood pressure. Although the unopposed use of estrogen is associated with an increased risk of endometrial cancer, this risk can be reduced or even neutralized by the addition of progestogen. The protection against cardiovascular disease provided by combined estrogen/progestogen treatment has been the subject of much debate. However, results from epidemiological studies, intervention trials and animal experiments now suggest that the addition of progestogen does not attenuate the beneficial effects of estrogen. While secondary prevention studies are needed to evaluate the various hormone regimens, the use of combined estrogen/progestogen therapy can be supported.
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PMID:Women at cardiac risk: is HRT the route to maintaining cardiovascular health? 938 12

Forty years ago, Lerner and coworkers (1958) discovered the first nonsteroidal antiestrogen and Jensen (Jensen and Jacobson, 1960) identified a target for drug action, the ER. This knowledge opened the door for the clinical development of tamoxifen which we now know provides a survival advantage in both node-positive and node-negative patients with ER-positive disease (Early Breast Cancer Trialists Collaborative Group, 1992, 1998). The drug has been studied extensively, and the results have provided an invaluable insight into possible ancillary advantages of "antiestrogens", i.e., maintenance of bone density and the prevention of coronary heart disease, and possible disadvantages, i.e., rat liver carcinogenesis and an increased risk of endometrial cancer. Most importantly, the identification of the target site-specific actions of tamoxifen caused a paradigm shift in the prospective uses of antiestrogens from a direct exploitation of the antitumor properties to the broader application as a preventative for osteoporosis, but with the beneficial side effects of preventing breast and endometrial cancer. Raloxifene, a second-generation SERM, has all the properties in the laboratory that would encourage development as a safe preventative for osteoporosis (Jordan et al., 1997). As a result, raloxifene has been evaluated in more than 11,000 postmenopausal women and found to maintain bone density with significant decreases in breast cancer incidence and no increase in endometrial thickness. Raloxifene is now available as a preventative for osteoporosis in postmenopausal women. There is every reason to believe that a multifaceted agent like raloxifene will find widespread use, and there will be continuing interest by the pharmaceutical industry in the development of new agents with even broader applications. The extensive clinical effort is augmented by past molecular innovations in the laboratory and the future promise of new discoveries. The cloning and sequencing of the ER (Green et al., 1986; Greene et al., 1986) has allowed the development of an ER knock-out mouse (Lubahn et al., 1993) that compliments Jensen's pioneering work (Jensen and Jacobson, 1962) and describes the consequences of the loss of ER alpha. However, ER beta (Kuiper et al., 1996), the second ER, has provided an additional dimension to the description of estrogen and antiestrogen action. For the future, the development of ER beta monoclonal antibodies, the classification of target sites for the protein around the body, and the creation of ER beta and ER alpha, beta knock-out mice will identify new therapeutic targets to modulate physiological functions. Clearly, the successful crystallization of ER alpha with raloxifene (Brzozowski et al., 1997) must act as a stimulus for the crystallization of ER beta. The central issue for research on antiestrogen pharmacology is the discovery of the mechanism (or mechanisms) of target site-specificity for the modulation of estrogenic and antiestrogenic response. The description of a stimulatory pathway for antiestrogens through an AP-1 ER beta signal transduction pathway (Paech et al., 1997), although interesting, may not entirely explain the estrogenicity of antiestrogens. The model must encompass the sum of pharmacological consequences of signal transduction through ER alpha and ER beta with the simultaneous competition from endogenous estrogens at both sites. This is complicated because estradiol is an antagonist at ER beta through AP-1 sites (Paech et al., 1997), so this is clearly not the pathway for estrogen-induced bone maintenance in women. Estrogen is stimulatory through ER alpha, but antiestrogens are usually partial agonists and may either block or stimulate genes. However, we suggest that the ER alpha stimulatory pathway could be amplified through selective increases in coactivators. The principle is illustrated with the MDA-MB-231 cells stably transfected with the cDNAs for the wild-type and the amino acid 351 mutan
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PMID:Basic guide to the mechanisms of antiestrogen action. 964 65

Tamoxifen offers protection against the development or recurrence of breast cancer in a range of clinical circumstances, while simultaneously helping to prevent osteoporosis and perhaps coronary heart disease. The most serious side effects of this antiestrogen are thromboembolism and accelerated development of endometrial carcinoma; they occur primarily in postmenopausal women.
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PMID:Preventing breast cancer with tamoxifen. 975 May 54

The purpose of this review is to assimilate relevant experimental and clinical information available on selective estrogen receptor modulators with respect to their potential use as agents to improve women's health in the postmenopausal years. In addition, the mechanisms of action of these drugs are outlined. Selective estrogen receptor modulators represent an exciting group of antiestrogens that possess agonist action on bone, lipids, and lipoproteins and antagonistic action in the endometrium and breast. Thus in theory these drugs may preserve bone density and reduce the risk of osteoporotic fracture and coronary heart disease at the same time that they lower the incidences of breast and endometrial neoplasms. Short-term data with the use of raloxifene suggest that bone is preserved and lipid profiles are less atherogenic. Long-term studies are needed to determine whether raloxifene or other selective estrogen receptor modulators are associated with any decrease in the risk of breast or endometrial cancer.
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PMID:Selective estrogen receptor modulators: Women's panacea for the next millennium? 1007 60

Coronary heart disease is the leading cause of death in women in the United States and increases dramatically in postmenopausal women. The following review summarizes the known benefits and risks of hormone replacement therapy and gives recommendations for use of hormone replacement in women. Estrogen may play a role in preventing the development of atherosclerosis in women by raising levels of HDL cholesterol, lowering levels of LDL cholesterol and lipoprotein (a), lowering levels of fibrinogen and plasminogen activator inhibitor-1, dilating coronary arteries, preventing the oxidation of LDL cholesterol, decreasing the proliferation and migration of smooth muscle cells, and decreasing the production of inflammatory cell activators. These antiatherogenic effects of estrogen may translate into clinical benefits. A meta-analysis of 31 studies yielded a 44% reduction in the risk of coronary heart disease in women taking estrogen alone. Unopposed estrogen is associated with an increased risk of endometrial cancer; therefore, progestin is added to estrogen in women with an intact uterus. Less is known about the effect of the combination of estrogen and a progestin on the risk of coronary heart disease. Estrogen is also beneficial in the prevention of osteoporosis; however, long-term use of estrogen alone and estrogen in combination with progestin may increase the risk for breast cancer. Mathematical modeling predicted that women with no risk for cardiovascular disease, cancer, or osteoporosis may gain 0.9 years of life with the use of estrogen alone; women with risk factors for cardiovascular disease can expect to gain 1.5 years of life; and women with coronary heart disease at the age of 50 can expect to gain 2.1 years of life. The current American College of Physicians recommendations for hormone replacement are as follows: (1) All women should be considered; (2) women with a hysterectomy should receive estrogen alone; (3) women at risk for, or with, coronary heart disease are most likely to benefit from estrogen; with an intact uterus, progestin must be added; (4) risks of estrogen may outweigh benefits in women at increased risk for breast cancer. Definitive guidelines for the treatment of women must await the results of randomized clinical trials in the ongoing Women's Health Initiative. These will not be available for several years, and until then any recommendations for women will have to be judged from estimates of risk rather than of benefit from reduction of risk. The decision whether to initiate estrogen replacement in postmenopausal women is one that still needs to be made on an individual patient basis.
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PMID:Who Should Receive Hormone Replacement Therapy? 1060 35

Knowledge of the mechanism of action and pharmacology of tamoxifen and raloxifene, for the prevention of breast cancer and osteoporosis respectively, has opened the door for the discovery of multifunctional medicines. There is now the potential to prevent osteoporosis, coronary heart disease, breast and endometrial cancer in postmenopausal women with elevated risk factors.
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PMID:Selective oestrogen receptor modulation: molecular pharmacology for the millennium. 1067 6


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