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

Estrogens play a crucial role in the regulation of the physiology of breast tissue and endometrium. Furthermore, estrogen has been implicated in the initiation and progression of neoplasms of these tissues. Estrogens mediate their effects through various estrogen receptor isoforms and isotypes. In breast tissue and in the endometrium the classical estrogen receptor ERalpha represents the mainly expressed ER isoform, whereas in the ovary the alternative estrogen receptor ERbeta is predominantly expressed. This review briefly describes the structure, function and expression of these receptors with special regard to endometrial cancer. Recent data indicate that alterations of the physiological ERalpha/ERbeta ratio in endometrial cancer correlates with poor clinical outcome. The potential clinical relevance of differential ER-isotype expression is also discussed with respect to an antihormonal therapy.
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PMID:[Role of estrogen receptor isoforms in the pathogenesis and treatment of endometrial cancer]. 1187 9

Recent reports suggest that the administration of estrogens to postmenopausal women is associated with an increased risk of developing endometrial cancer. Although the evidence is indirect, it is consistent with the recent introduction into the population of a carcinogen whose primary effect is on the endometrium. Estrogens have often been prescribed for trivial reasons and have been taken for long periods. The median reported length of estrogen use has been 10 years. There is a latency period in the carcinogenic effect so a more frequent incidence of endometrial carcinoma may yet follow. In the meantime, use of estrogens for specific menopausal symptoms is justified. There is less concern in prescribing estrogens for hysterectomized patients. Most emotional problems are better handled by counseling or short-term use of sedatives or tranquilizers. Senile osteoporosis may be benefited by estrogen therapy. Following oophorectomy early in life estrogen treatment may retard onset of osteoporosis but cannot reverse the aging process. Cyclic administration of estrogen use is advised with the lowest effective dose. Vasomotor symptoms require temporary treatment but atrophic vaginitis needs longer therapy. Reevaluation of patients at 6-month intervals at first and then yearly is recommended. A Papanicolaou smear should include material from the endometrial canal. Abnormal bleeding requires investigation. The patient should be informed regarding risks and benefits of estrogen therapy.
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PMID:Estrogens and menopause. 1230 3

Recent studies have demonstrated new benefits of pill use, reduced risks associated with the minipill, and the possibility of screening out high risk women. The minipill is as effective as other formulations except in cases of chronic malnutrition or concomitant use of antibiotics or anticonvulsives. Oral contraceptives (OCs) frequently lessen menstrual problems. They prevent functional cysts in the ovaries, and reduce the incidence of benign breast tumors and the relative risk of developing ovarian cancer after 3 years of use. Combined OCs reduce the risk of endometrial cancer although sequentials increase it. OCs offer protection against salpingitis and other pelvic infections, against tubal pregnancies, and against chronic rheumatoid arthritis. Minipills appear to be less frequently associated with bothersome side effects than other OCs. The most significant risk of OCs is of death due to thrombo emboli of venous origin, myocardial ischemia, cerebrovascular accidents, and hypertension in women over 35, particularly those who smoke heavily. In 1981 the 2 British studies reported a reduced risk from these causes compared to results published in 1977. Estrogens are clearly responsible for some of the complications, apparently due to a weakening of the fibrinolytic systems, but progestagens or estrogen-progestagen combinations are also implicated. Arterial hypertension and cerebral and cardiac accidents appear to be due to the effect of progestagens on arterial tension, glucose metabolism, and the level of high density lipoprotein cholesterol. Risks of some liver diseases are elevated in pill users, but the question of tumors of the pituitary is not yet resolved. The incidence of uterine cancer appears to be elevated in pill users although the association is obscured by other factors. Some evidence exists of an association between estrogen-progestagen formulations and melanoma. No increase in abortion or fetal malformations except possibly an increase in twin pregnancies is noted after discontinuation of the pill. Pills should not be prescribed for smokers over 35 or any women over 45. Pills are possibly acceptable for women 35-44 in good health with no signs of diabetes, hypertension, or hyperlipoproteinemia. They should be followed up more frequently and should recognize the signs of complications.
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PMID:[Oral contraception in 1983 (author's transl)]. 1231 9

Postmenopausal estrogens originate from the peripheral conversion of androgens, which are produced by the adrenal glands and the ovaries. Estrogens are considered to contribute to the neoplastic development of endometrium. Hyperplasia of ovarian stroma is associated with an increased androgen production by the ovaries and with the development of endometrial pathology. We hypothesize that, in cases of endometrial pathology, an increased production of aromatizable androgens by postmenopausal ovaries will lead to elevated prehormone availability for estrogen formation in utero. Following the conversion of ovarian androgens, a reaction catalyzed by the cytochrome p450 aromatase, estrogens may function as a local mitogenic factor eventually leading to the development of endometrial cancer. We consider the local availability of androgens and the local activity of aromatase relevant for this process. If this hypothesis proves to be right it may give rise to the introduction of aromatase inhibitors in treatment strategies of hormone dependent endometrial malignancies.
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PMID:The postmenopausal ovary as an androgen-producing gland; hypothesis on the etiology of endometrial cancer. 1238 55

Estrogens act through specific receptors located in the nuclei of epithelial and stromal cells of the endometrium. Estrogens stimulate the synthesis of these receptors and the progesterone inhibits their synthesis. Estrogens induce the proliferation of the mucosa during the proliferative phase. They also stimulate the synthesis of receptors for the progesterone, which is a prerequisite for progesterone activity. Hyperplasias most of the time do not contain cytological atypia and are developed under a hyperestrogenic background. They contain receptors for estrogen and progesterone, and are able to respond to progestogens. Hyperplasias with cytological atypia are precancerous lesions, associated with an hyperestrogenic or atrophic background. In the later case, they may be focal and are better diagnosed by hysteroscopy. They are best managed by simple hysterectomy. Progesterone may be used if the patient desires to conceive. Endometrial cancers are either associated with an hyperestrogenic or atrophic background. In the later case, they are often of serous or clear cell type. Endometrial effects of antiestrogens are known only for tamoxifene. Tamoxifene has an atrophic effect but sometimes may induce an estrogenic stimulation of the endometrial mucosa through the alpha and beta estrogenic receptors. Polyp is the most frequent abnormality diagnosed but endometrial cancer is significantly more frequently diagnosed than in a control population. It is well differentiated and does not modify the survival of the patient.
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PMID:[Effect of estrogens and antiestrogens on the endometrium]. 1266 Dec 81

It is well accepted that unopposed estrogens increase the risk of developing endometrial cancer. A relationship between estrogen exposure and the risk for breast cancer is very probable. In addition, an association of long-term estrogen substitution and ovarian cancer risk has been postulated recently. Estrogens have been considered as typical tumor promotors. Due to their estrogen-receptor-mediated mitogenic activity, these steroids were supposed to increase the statistical probability of spontaneous mutations. Recent experimental findings, however, suggest that estrogen metabolites, in particular 4-hydroxyestrogens are capable of inducing DNA-damage and transforming mutations. The clinical relevance of these genotoxic properties of estrogens remains to be established, but could obtain great importance. First molecular-epidemiologic studies suggest that due to the specific activity of their estrogen metabolizing enzymes some women might produce relevant amounts of mutagenic estrogen metabolites, increasing their risk for breast-, endometrial- or ovarian cancer respectively. These findings might result in novel preventive strategies. The present data do not justify to abandon the practice of hormone replacement therapy with estrogens or estrogens plus progestins in non hysterectomised women. It seems to be wise, however, to restrict hormone replacement therapy to symptomatic women with a clear indication and, according to the actual trend, limit it temporarily.
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PMID:[Are estrogens carcinogens?]. 1282 69

The incidence of endometrial cancer and ovarian cancer in Japan has been increasing in recent years. Results of epidemiologic studies suggest that the onset and multiplication of these cancers are associated with estrogen. Estrogens are metabolized by cytochrome P450 1A1 (CYP1A1) and converted into catecholestrogens, which are carcinogens. CYP1A1 has several polymorphisms, the major one being T6235C transition in the non-coding 3'-flanking region (MspI polymorphism), and another being A4889G transition in exon 7 (Ile/Val polymorphism). These polymorphisms can affect the metabolites of estrogens and contribute to the susceptibility to gynecological malignancy. In this study, to determine whether CYP1A1 polymorphism plays a role in the development of gynecological malignancy in the Japanese population, we assessed the association of CYP1A1 polymorphism in Japanese patients with gynecological malignancy in comparison to that in controls. The odds ratios (ORs) of Ile/Val polymorphism were 1.16 in ovarian cancer patients and 1.70 in endometrial cancer patients. The ORs of MspI polymorphism were 1.33 in ovarian cancer patients and 0.88 in endometrial cancer patients. No significant association was found between these CYP1A1 polymorphisms and gynecological malignancy. Although the frequency of CYP1A1 polymorphism in the Japanese population is higher than that in the Caucasian population, CYP1A1 polymorphism is not related to gynecological malignancies in Japanese population.
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PMID:CYP1A1 polymorphism and risk of gynecological malignancy in Japan. 1467 15

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

In situ estrogen metabolism and synthesis have been considered to play a very important role in the development and progression of human endometrial carcinoma. 17Beta-hydroxysteroid dehydrogenases (17-HSDs) are enzymes involved in the formation of active sex steroids, including testosterone, estrone (E1) and estradiol (E2). Estrogens are interchanged by two enzymes, 17-HSD types 1 and 2, type 1 converts E1 to E2, and type 2 does reverse actions. 17-HSD type 5 catalyzes the reduction of androstenedione to testosterone. 17-HSD type 2 expression was decreased through normal endometrium, hyperplasia and carcinoma accordingly. There was a significant inverse correlation between intratumoral E2 concentration and the level of 17-HSD type 2 mRNA in endometrial carcinoma. 17-HSD type 5 expression was significantly increased through normal endometrium, hyperplasia and carcinoma accordingly. These results indicated that 17-HSD types 2 and 5 play an important role in the regulation of in situ estrogen production in endometrial carcinoma.
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PMID:17Beta-hydroxysteroid dehydrogenases in human endometrium and its disorders. 1640 63

Hormone replacement therapy (HRT) has become available over the past few decades, but the risk of breast cancer with HRT remains controversial. The Women's Health Initiative Study has recently demonstrated that women receiving estrogen plus progestin (HRT) have an increased risk of invasive breast carcinoma, although women receiving estrogen alone (estrogen replacement therapy) exhibit no increased risk of breast carcinoma. By contrast, the risk of endometrial carcinoma increases with estrogen replacement therapy, while HRT reduces the risk of endometrial carcinoma. These clinical findings suggest that the biological roles of estrogen and progestin in tumorigenesis are certainly different between the endometrium and breast, although both are considered "estrogen-dependent tissues". In this review, I summarize the recent studies and indicate that the enzymes responsible for intratumoral estrogen metabolism and biosynthesis are markedly different between human breast and endometrial carcinomas. 17beta-hydroxysteroid dehydrogenases (17-HSDs) are enzymes estrogen replacement therapyinvolved in the formation of active sex steroids. Estrogens are interconverted by two enzymes, 17-HSD types 1 and 2. Type 1 converts estrone to estradiol, and type 2 catalyzes the reverse reaction. 17-HSD type 5 reduces androstenedione to testosterone. 17-HSD type 1 plays an important role in the regulation of high estradiol levels in breast carcinoma tissues, whereas 17-HSD types 2 and 5 appear to be essential for the maintenance of estradiol concentrations in endometrial carcinoma tissues. In addition, the biological significance of progesterone receptor isoforms differs between endometrial and breast carcinomas. These findings may provide new insights into the biology of "estrogen-dependent tissues".
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PMID:Hormone replacement therapy and cancers: the biological roles of estrogen and progestin in tumorigenesis are different between the endometrium and breast. 1746 97


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