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

For many years hormonal replacement therapy (HRT) has been considered to offer not only effective relief of climacteric symptoms but also a reduction in the risk of osteoporosis and cardiovascular disease, plus a possible prevention of cognitive decline. Randomised trials of HRT in women with preexisting coronary heart disease have not confirmed, however, cardiovascular benefits of HRT and have even suggested increased cardiac risk associated with this management. Numerous retrospective studies demonstrated that the risk of breast cancer is higher in HRT-users and is related to therapy duration. More recent studies suggested that breast cancer risk increases further if oestrogen is coupled with progestogen. On the other hand, some data show that breast cancers diagnosed in women during HRT administration may be less aggressive. Typically, tumours in these patients are smaller and better differentiated. HRT also increases the relative risk of endometrial cancer, particularly if oestrogen alone is administered. Currently, the indications for HRT in healthy subjects should include only reduction of menopausal symptoms and prevention of osteoporosis. The use of HRT in breast cancer survivors is controversial, and until the results from prospective randomised trials are available, cannot be recommended in this group as a standard care.
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PMID:The risks and benefits of hormonal replacement therapy in healthy women and in breast cancer survivors. 1297 54

Although hormone replacement therapy (HRT) is used by post-menopausal women for the relief of menopausal symptoms and the potential reduction of osteoporosis, HRT also increases their risk of Alzheimer's disease, stroke, breast cancer, and endometrial cancer. Since the majority of these effects are associated primarily with estrogen binding to only one of the estrogen receptors (ER), new assays are needed that can more efficiently evaluate ER-binding and identify ligands selective for ER-alpha and ER-beta. High performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) was combined with ultrafiltration as a new method to investigate the relative binding of compounds to the ERs and to evaluate the structures of these estrogens. Mixtures of estradiol and six equine estrogens, including equilin, equilenin, 8,9-dehydroestrone, and their 17beta-hydroxyl derivatives, were assayed simultaneously to determine their relative binding to human ER-alpha and ER-beta. Estrogens containing a 17beta-OH group were found to have higher relative affinities for the estrogen receptors than their ketone analogs. In addition, 17beta-EN showed selectivity for binding to ER-beta over ER-alpha. The results were compared to the IC50 values obtained by using a conventional radiolabled estradiol competitive binding assay. Finally, the utility of negative ion electrospray tandem mass spectrometry for the unambiguous identification of these estrogen isomers was investigated. Several characteristic recyclization pathways during tandem mass spectrometry were identified, which might be useful for distinguishing related estrogens.
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PMID:Ultrafiltration tandem mass spectrometry of estrogens for characterization of structure and affinity for human estrogen receptors. 1569 77

The US Food and Drug Administration (FDA) approved marketing of diethylstilbestrol in 1941 and conjugated equine estrogens (CEE) in 1942 for treatment of menopausal symptoms. Estrogen sales doubled and tripled in the mid-1960s to mid-1970s, until 1975, when reports of increased endometrial cancer in estrogen users resulted in a dramatic decline. Estrogen use increased again, with evidence of protective effects of progestins on estrogen-induced endometrial changes, combined with a 1982 report that Premarin (conjugated estrogen tablets; Wyeth Pharmaceuticals, Philadelphia, PA) retained bone mass and a 1984 National Institutes of Health (NIH) Consensus Conference on Osteoporosis statement that estrogens were the most effective means for preventing bone loss. Despite conflicting reports in 1985 regarding the relation between estrogens and coronary heart disease (CHD), many published observations of reduced CHD risk in estrogen users--reinforced by clinical trial findings in 1995 of favorable lipoprotein changes in women assigned to CEE with or without a progestin--promoted increased use through the 1990s. By 2001, approximately 15 million US women were using estrogen therapy, with or without progestins. The 2002 Women's Health Initiative (WHI) report of greater harm than benefit of combined CEE plus a progestin resulted in a precipitous decrease in estrogen and progestin use and a serious reevaluation of menopausal hormone therapy, as well as increased interest in alternative approaches to managing menopausal symptoms, including use of "bioidentical" hormones. FDA guidelines regarding treatment indications for vasomotor symptoms, vaginal atrophy, and osteoporosis prevention have resulted in approval of several estrogen (and progestin) formulations, doses, and routes of administration, thereby providing many options for women who seek conventional therapy.
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PMID:Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration. 1641 29

(1) In 2004, the first results of the British Million Women Study, a prospective cohort study that included more than a million women, showed that women using tibolone had nearly 1.5 times the risk of breast cancer as women who never used hormone replacement therapy. The difference was statistically significant. (2) In 2005, after a mean follow-up of 3.4 years, there were 31 cases of endometrial cancer per 10 000 women who used tibolone. This was almost double the level of risk experienced by women who never used hormone replacement therapy. (3) In another British cohort study, based on a general practice database, the risk of endometrial cancer among 4995 women treated with tibolone was almost double that of women who used sequential estrogen-progestin hormone replacement therapy. (4) Tibolone has no proven advantage over estrogen-progestin hormone combinations for treatment of symptoms of menopause, either in terms of efficacy or cancer risks. It is associated with an increased risk of stroke. There is no justification for using tibolone as a treatment for menopausal symptoms.
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PMID:Tibolone: cancers of the breast and endometrium. 1676

A literature search was performed to collect information concerning hormone replacement therapy (HRT) for menopausal symptoms by exogenous steroids and breast and endometrial cancer risk. Relevant studies in English were selected from Medline. HRT can alleviate vasomotor symptoms at least partially. HRT in women >50 years of age induces increased risk of breast and endometrial cancer. In women <50 years of age, HRT does not completely negate the breast cancer risk reduction by premature menopause. No data exist on endometrial cancer risk in these young women taking HRT. In conclusions, the decision to use HRT should be weighed against the risks and discouraged in women older than 50 years of age and after breast cancer. Counseling should be performed in an individual manner.
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PMID:Exogenous steroids for menopausal symptoms and breast/endometrial cancer risk. 1701 54

We describe three women who developed endometrial cancer after taking "bioidentical" hormone replacement therapy (HRT) to relieve menopausal symptoms. Although pharmaceutical HRT is a well established and tested therapy, little is known about the quality control, safety and efficacy of bioidentical HRT. Women should be advised to avoid bioidentical HRT, and those who continue to use it should receive regular endometrial surveillance.
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PMID:Three cases of endometrial cancer associated with "bioidentical" hormone replacement therapy. 1770 28

Hormone replacement therapy (HRT) has been used worldwide to relieve menopausal symptoms. The evolution in clinical knowledge of its risks has lagged persistently behind its application in clinical practice. In the 1970s, endometrial cancer incidence increased in developed countries, and exogenous estrogen therapy in postmenopausal women was the most important factor. In the 1980s and 90s, combined estrogen-progesterone therapy was prescribed on a large scale, based on its potential beneficial effects on the musculoskeletal and cardiovascular systems without increasing the risk of endometrial carcinoma. However, once again, recent reports argue against the safety of HRT, and the most important issues are now the increased risk of cardiovascular disease and total cancer in combined formulations. We conclude that the recently reported risks on combined HRT may have a significant public health impact, and that this treatment regimen should not be prescribed to protect postmenopausal women from endometrial carcinoma, since the risks outweigh the benefits.
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PMID:[Hormone replacement therapy and endometrial cancer]. 1795 54

The use of aromatase inhibitors (AIs) as adjuvant endocrine therapy for hormone-sensitive breast cancer is increasing, as these drugs are more effective than tamoxifen alone in improving disease-free survival in breast cancer patients-whether used in lieu of tamoxifen as upfront therapy or after tamoxifen treatment periods of 2 years or longer. AIs differ from tamoxifen in their mechanism of action, effectively suppressing estrogen levels in postmenopausal women to near-undetectable levels. AI-associated adverse events largely mimic menopausal symptoms, including hot flashes, losses in bone mineral density, gynecologic symptoms, and arthralgias. The AIs lack the infrequent but potentially serious adverse events associated with tamoxifen (eg, endometrial cancer, thromboembolic events, and stroke). Large randomized studies of AIs in the adjuvant setting have not demonstrated an adverse effect on lipids and cardiovascular health, but postmenopausal women receiving AIs are at risk for age-related changes in lipid parameters and an increased risk for cardiovascular events. To optimize the overall benefits of adjuvant endocrine therapy with an AI, patients should be monitored for bone loss and cardiovascular risk factors, and symptoms such as joint pain and vaginal dryness should be anticipated and managed proactively.
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PMID:Safety of adjuvant endocrine therapy in postmenopausal women with breast cancer. 1906 May 94

Estradiol and related estrogens have been widely used as supplements to relieve menopausal symptoms, but they lead to an increased risk of breast and endometrial cancer. Here we report the synthesis of a new family of compounds where we have removed the B-ring from the steroid ABCD structure, and functionalized the A-ring. These A-CD compounds show a preferential affinity for the estrogen receptor subtype ERbeta. Some show binding affinities which are greater than estradiol. The presence of electron-withdrawing substituents on the A-ring should reduce the tendency of these compounds to form carcinogenic metabolites, so they might lead to a safer approach to hormone replacement therapy.
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PMID:Deconstructing estradiol: removal of B-ring generates compounds which are potent and subtype-selective estrogen receptor agonists. 1916 82

This article reviews publications dating back more than a century describing investigations of the endometrium, including those examining the relationship between endometrial hyperplasia and carcinoma, the influence of estrogens on the endometrium, and strategies for protecting the endometrium from unopposed estrogen stimulation. Endometrial hyperplasia and carcinoma studies date from before 1900. The influence of endogenous estrogens on the endometrium became evident with observations of endometrial hyperplasia and/or carcinoma in women with estrogen-secreting tumors or polycystic ovarian disease. Later, observational studies and randomized, controlled trials suggested a relationship between unopposed estrogens and endometrial cancer and hyperplasia. The first, and to date only, effective clinical strategy for protecting the endometrium from unopposed estrogen stimulation has been the use of progestins. A new approach for endometrial protection in menopausal therapy is the pairing of a selective estrogen receptor modulator (SERM) with estrogen(s), also known as a tissue selective estrogen complex (TSEC). Effective protection of the endometrium as well as treatment of menopausal symptoms and prevention of osteoporosis would be key elements for a clinically useful TSEC.
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PMID:The endometrium--from estrogens alone to TSECs. 1990 99


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