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

In western countries more than 30% of the female population are postmenopausal. Approximately 30% of postmenopausal women suffer from clinical symptoms of the climacteric such as vasomotor symptoms, associated with hot flushes, night sweat, insomnia and depressive mood. Sufficient hormonal replacement therapy (HRT) will abolish specific menopausal symptoms in over 90% of patients, unspecific symptoms such as headache respond to placebo and HRT equally well. The question of cancer risk related to HRT will be addressed in this review. In combination with progestins, estrogens are obviously protective regarding ovarian and endometrial cancer. The association between HRT and breast cancer risk is presently unclear. Epidemiological data available so far do not provide compelling evidence as to a cause and effect relationship between HRT and breast cancer risk. There seems to be an overall trend towards a slightly increased risk with increasing duration of HRT use. Guidelines for HRT use in women with a history of endometrial and breast cancer are provided in this article.
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PMID:Benefits and risks of hormone replacement therapy (HRT). 762 55

The use of estrogens in postmenopausal women has been the subject of much controversy regarding hormone formulation, dosage, use in combination with progestins, duration of treatment, and contraindications. Estrogens have been prescribed to relieve menopausal symptoms for more than three decades. The hormones reduce the gynecologic and psychologic changes associated with menopause while inhibiting bone resorption and possibly reducing the risk of cardiovascular disease. Their use however has been complicated by an increased risk of endometrial cancer and possibly breast cancer. The use of estrogens as cardioprotective agents is discussed and the clinical experiences and the possible mechanisms of action are reviewed. The clinical pharmacology of estrogens and the various formulations that are available as monotherapy or in combination with progestins will also be reviewed.
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PMID:Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women. 760 24

Several lines of evidence suggest that estrogen is an important determinant of cardiovascular risk in women. Epidemiologic data document low rates of coronary heart disease (CHD) in premenopausal women, a narrowing of the gender gap in CHD mortality after menopause, and elevated risk of CHD among young women with bilateral oophorectomy not treated with estrogen. Nearly all of the more than 30 observational studies of exogenous estrogen replacement therapy have indicated a reduced risk of CHD among women receiving estrogen therapy. In a meta-analysis comparing estrogen users and nonusers, the estimated reduction of CHD among users was 44%. In angiographic studies, women taking estrogen were less likely to have coronary artery stenosis. Estrogen is known to affect a wide range of physiologic processes that may have an impact on CHD risk. Use of oral estrogen has favorable effects on serum lipid profiles; it increases high-density lipoprotein cholesterol levels by 10% to 15% and decreases low-density lipoprotein cholesterol levels by a similar magnitude. Other proposed mechanisms include inhibition of endothelial hyperplasia, reduced arterial impedance, enhanced production of prostacyclin, increased insulin sensitivity, and inhibition of oxidation of low-density lipoprotein. Nevertheless, the role of hormone replacement therapy in preventing clinical atherosclerotic events in women remains inconclusive because of the absence of randomized trial data. The benefit-to-risk ratio must be reliably assessed, because estrogen has complex actions, including postulated benefits (CHD, osteoporosis, and menopausal symptoms) and postulated risks (endometrial cancer, breast cancer, and gallstones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postmenopausal hormone therapy and atherosclerotic disease. 797 16

As more women are living longer, there is an increasing need for women to discuss hormone replacement therapy (HRT) with their physicians. This task is complicated by areas of scientific uncertainty and evolving data concerning the risks and benefits of HRT. Benefits of HRT that are supported by strong scientific evidence include relief from menopausal symptoms such as hot flashes, prevention of osteoporosis, cardioprotective effects, relief of urogenital atrophy, and decreased urinary incontinence. Benefits supported by observational evidence include improvement of emotional lability and depression, improved sense of well-being in patients with rheumatoid arthritis, increased dermal and total skin thickness, improved verbal memory skills, and decreased risk of colon cancer. Risks to consider include a possible increase in the incidence of breast cancer and an increase in endometrial cancer in women who have an intact uterus and do not receive a progestin. Women in various risk groups, such as those at risk for coronary artery disease, osteoporosis, or breast cancer, must consider the risk-to-benefit ratio for their own individual circumstances.
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PMID:Current concepts in postmenopausal hormone replacement therapy. 869 Nov 83

Hormone replacement therapy (HRT) provides relief of menopausal symptoms, reverses atrophic urogenital changes, prevents osteoporosis, and produces favorable lipoprotein effects. Continuous combined HRT using 2.5 mg of medroxyprogesterone was designed to increase patient compliance by eliminating withdrawal bleeding while at the same time retaining the beneficial effects of HRT. There are limited long-term data, however, regarding the safety of continuous combined HRT. Of concern are reports of endometrial carcinoma arising in women receiving continuous HRT with low-dose progestin. Eight cases of women who developed endometrial carcinoma while on this regimen are presented. The possible increased risk of endometrial cancer associated with this regimen may be related to inadequate progestin dose, prior use of unopposed estrogen, poor patient compliance, use of less effective progestins, less efficient reversal of hyperplasia, and the use of progestin continuously.
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PMID:Continuous low-dose combined hormone replacement therapy and the risk of endometrial cancer. 906 44

Oestrogen replacement therapy (ORT) significantly increases the relative risk (RR) of endometrial cancer, especially long-term oestrogen use (RR: 9.5; 95% confidence interval (CI): 7.4-12.3). Addition of a progestin to ORT reduces this increased risk completely or largely. The risk of breast cancer is increased after ORT of 5 years or longer (RR: 1.23; 95% CI: 1.08-1.40). Addition of a progestin does not reduce this increased risk. The possibility cannot be excluded that long-term ORT increases the risk of epithelial ovarian cancer. No significant association between ORT and cervical cancer has been demonstrated. It is safe to prescribe ORT for a period shorter than 5 years for women with menopausal symptoms. Addition of a progestin is indicated when the uterus is in situ. Hormonal supplementation therapy is to be discouraged in women treated for breast cancer, may be considered in young women previously treated for endometrial or ovarian cancer with a good prognosis and severe menopausal symptoms and is justified in women previously treated for cervical cancer.
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PMID:[Postmenopausal hormone replacement therapy and cancer of the female genitalia and breast]. 915 96

The well-described influence of several aspects of reproductive life on the risk for cancer in the reproductive organs has raised concern regarding the safety of exogenous hormones, particularly since sex hormones have become one of the most widely used drugs among women in the western world. The major areas of application include oral contraception and hormone replacement therapy in women with menopausal symptoms. Since the introduction of oral contraceptives onto the Nordic market in the late 1960s, the number of users has grown steadily, to reach proportions of long-term users among women aged 15-45 years in 1985 ranging between 6% (Norway) and 19% (Sweden) and proportions of current users in 1994 ranging between 20% (Norway) and 28% (Sweden). Such data on the current and long-term use of oral contraceptives by the female populations, linked with relative estimates of adverse (cancers of the breast and uterine cervix) and beneficial effects (protection against cancers of the ovary and endometrium), indicate that 95 cases of breast cancer and 40 of cervical cancer will be caused by oral contraceptives annually around 2000 in the Nordic countries, which corresponds to 0.6% of all breast cancers and approximately 3% of all cervical cancers. The beneficial effects include an annual prevention around the year 2000 of approximately 350 cases of ovarian cancer and a similar number of endometrial cancer, for a total about 700 cancer cases annually. The prevalence of long-term users (> or = 5 years) of hormone replacement therapy among Nordic women aged 40-69 in 1995 was estimated to be 10-11%, which on the basis of an associated relative risk for breast cancer ranging from 1.2-1.5 suggests than an annual total of 260 cases of breast cancer could be avoided in the Nordic countries around the year 2000 if hormone replacement therapy were eliminated. This corresponds to 1.8% of all notified cases of breast cancer among women in these countries.
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PMID:Avoidable cancers in the Nordic countries. Exogenous hormones. 946 25

Hormone replacement therapy (HRT) acts both as an effective treatment of menopausal symptoms and genital atrophy, and as an effective prevention of osteoporosis. It is also probably cardioprotective and potentially preventing cerebrovascular disease. The risk of oestrogen-induced endometrial cancer is eliminated by the addition of a progestin. An increase in breast cancer risk is however possible after 10 years or more of HRT use. This multifactorial risk-benefit balance altogether with other variables (numerous and expensive hormonal therapies, low compliance of postmenopausal women, need for monitoring, therapy-related adverse events) explain why so few global pharmaco-economic appraisals have been devoted to HRT. Computer model studies have been set up to study hypothetical cohorts of menopausal women treated for 5-10 years or more, comprising hysterectomized women (receiving an estrogen alone) and non hysterectomized women (receiving an oestrogen-progestogen therapy) compared with untreated controls. Treatment of hysterectomized women as well as non hysterectomized symptomatic menopausal women appears relatively cost-effective. In terms of mortality and morbidity, a reduction in cardiovascular disease risk and, to a smaller extent, in osteoporosis has a strikingly greater impact than the small increase in breast cancer risk related to HRT use. A significant increase in life expectancy seems associated with long-term use and the quality-adjusted life years gain, is particularly impressive, as quality of life appears distinctly improved by HRT utilization. In the future, this beneficial cost-effectiveness equation will probably be optimized thanks to the introduction of alternative and innovative replacement therapies allowing longer treatment periods without increasing the risk of breast cancer.
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PMID:[Risks, benefits and costs of hormone replacement therapy in menopause]. 968 87

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

Age is the most important risk factor for the development of breast cancer. The risk of breast cancer continues to increase in American women until the age of 80 years. A family history of breast cancer helps identify those who possibly have the highest risk of developing breast cancer; however, most women who develop breast cancer do not have a first-degree relative with a history of breast cancer. Currently, the Gail model is a commonly used model to identify risk, and this model has now been validated in several populations of women undergoing screening for breast cancer. The first large-scale breast cancer prevention trial investigating the preventive effects of tamoxifen has demonstrated a decrease in the development of breast cancer by almost 50% in the women in the tamoxifen treatment arm as compared with those receiving placebo. The NSABP P-1 trial was the largest of the three tamoxifen breast cancer prevention trials and had the greatest power to detect a difference between the two treatment groups in breast cancer events. This trial also included the largest percentage of postmenopausal women. It is unclear why the Italian and Royal Marsden Hospital trials had negative results regarding the preventive effects of tamoxifen. These two trials were strikingly different from the NSABP P-1 trial, however, and they included a different population of women. The issues surrounding the use of HRT for treatment of hot flashes in the Italian and Royal Marsden Hospital trials adds to the controversy concerning the negative results of these trials. The new SERM, raloxifene, has shown promise in preliminary studies as a preventive agent for breast cancer. The STAR trial will open soon and will evaluate the efficacy of raloxifene in preventing breast cancer in a prospective fashion, comparing its efficacy with tamoxifen treatment. Other endpoints will evaluate side effects such as menopausal symptoms, endometrial cancer, thromboembolic events, and benefits regarding serum lipids and incidence of osteoporotic bone fractures. The development of SERMs results from an understanding of novel mechanisms of ER modulation and allows targeting for favorable effects in specific tissues. The challenge is to develop an ideal SERM that is effective in preventing breast cancer and does not increase the risk of endometrial cancer, while providing beneficial estrogenic effects on serum lipids and bone mineral density changes. Estrogen receptor-mediated intracellular processes are complex. There are at least two different types of estrogen receptors. The alpha receptors predominate in the breast and uterus, and the beta receptors predominate in the bone and blood vessels. Many proteins also interact with these receptors as co-activators or co-repressors. Transcription-activating factors modulate the effects of estrogen on its target genes. Future prevention strategies may use a combined targeted approach to inhibit ER-mediated cancer progression pathways. The retinoids are under investigation in prevention studies for a multitude of cancers, because they have been shown to inhibit cellular proliferation and to induce cellular differentiation. The retinoid 4HPR was selected for use in breast cancer prevention studies because of its low toxicity profile and prevention efficacy in preclinical studies. It is now being used in combination with tamoxifin in a phase II breast cancer prevention trial. Multiple surrogate endpoint biomarkers are being measured before and after treatment, including measurement of serum IGF-I levels. Future directions in breast cancer prevention include the development of more potent hormonal therapies that completely inhibit ER-mediated cancer progression and, ultimately, multitargeted therapies involving agents that work synergistically.
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PMID:Chemoprevention of breast cancer in the older patient. 1068 75


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