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

Polycystic ovary syndrome [PCOS] is the most common endocrinopathy of women in reproductive age. An association between PCOS and type-1 endometrial cancer has often been reported in the literature. The prolonged anovulation with consequent continued secretion of estrogen unopposed by progesterone may enhance the development and growth of this malignancy, particularly in young women. Hypersecretion of luteinizing hormone [LH], chronic hyperinsulinemia and increased serum insulin-like growth factor [IGF]-I levels may represent risk factors for endometrial cancer. However, data available in the literature do not allow a meta-analysis to be carried out to calculate an estimate of the relative risk of endometrial cancer in women with PCOS. Anecdotal cases of low-grade endometrial stromal sarcoma and carcinosarcoma have been reported in association with prolonged unopposed estrogen stimulation, and in particular with PCOS. A few studies have addressed the possibility of an association between PCOS and epithelial ovarian cancer risk, and the results are conflicting but generally reassuring, and similarly the few available data appear to exclude a strong association between PCOS and breast cancer.
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PMID:Polycystic ovary syndrome and gynecological cancers: is there a link? 1601 62

Polycystic ovarian syndrome is a common disorder associated with a significant long-term risk of developing type 2 diabetes and cardiovascular diseases. Insulin resistance and hyperinsulinemia play an important role in its pathophysiology and therefore insulin sensitizers have been proposed as a possible treatment option for this condition. In this review, pertinent literature is described that supports the use of insulin sensitizers for the management of short-term (fertility and hyperandrogenism) as well as long-term (type 2 diabetes, cardiovascular diseases and endometrial cancer) clinical issues of the syndrome. There is sufficient evidence in the literature to support the initial use of insulin sensitizers for fertility and the chronic treatment of hyperandrogenism. Furthermore, insulin sensitizers may prevent type 2 diabetes or cardiovascular diseases, whereas some evidence suggests that oral contraceptives could increase these risks. Therefore, although oral contraceptives may provide a more reliable control of menstrual disorders, insulin sensitizers should be considered as a preferential treatment option in women with polycystic ovarian syndrome at an increased risk of developing type 2 diabetes or cardiovascular disease, especially if they do not need contraception.
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PMID:Use of insulin sensitizers in polycystic ovarian syndrome. 1625 22

Polycystic ovary is characterized by anovulation, hyperandrogenemia and insulin resistance. Hyperinsulinemia is known to be associated with an increase in cardiovascular risk and the development of diabetes mellitus. The finding that insulin resistance has important implications in the pathogenesis of polycystic ovarian disease has elicit the concept of a therapeutic approach of insulin-sensitizing drugs. Last decade multiple clinical trials about these drugs and upon genesis of polycystic ovary were designed; hence there is now sufficient evidence in the literature to support its clinical use. The management of polycystic ovary includes short-term objectives, such as treatment of infertility and control of androgen excess, as well as long-term considerations, such as prevention of endometrial cancer and management of dysmetabolic syndrome with its associated risk for developing type 2 diabetes and cardiovascular disease. The present review justifies the rationale use of insulin-sensitizing drugs in order to treat both short-term and long-term issues regarding polycystic ovarian disease.
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PMID:[Insulin sensitizers in the treatment of polycystic ovary]. 1630 38

Atypical endometrial hyperplasia has been associated with progression to endometrial cancer, the most common genital malignancy. There are multiple risk factors for endometrial cancer, such as early menarche, exogenous estrogen exposure, obesity and diabetes. Diabetics have a 3-4 fold relative risk of endometrial cancer. Also, several studies have demonstrated an association between insulin resistance and endometrial cancer. There is known the first description of atypical endometrial hyperplasia resistant to progestogen therapy, which was subsequently treated with an insulin-sensitizng agent, metformin. Metformin is a biguanide antihyperglycemic agent used in the treatment of adult-onset diabetes. Unlike the sulfonylureas, metformin does not act primarily by increasing insulin secretion. In contrast, metformin lowers the rate of gluconeogenesis in the presence of insulin. Therefore, it is considered an insulin-sensitizer. Increased insulin sensitivity may improve the metabolic effect of insulin and decrease its mitogenic effect by tissue-specific mechanisms. One explanation for tissue specific differences in insulin binding and action may be through the relative expression of the insulin receptor (IR) isoforms. The IR isoforms IR-A and IR-D differ by 12 amino acid residues, owing to the alternative splicing of exon. The IR-A is predominantly expressed in malignant tissues and may lead to mitogenic effects within the cell. The relative expressions of IR-A and IR-B in normal and malignant endometrial tissue is not known. Besides direct effects on the IR, several additional mechanisms have been proposed for the mitogenic effect of insulin in endometrial cancer. In addition to the possible direct mitogenic effects of insulin through the IR-A, insulin resistance may be associated with alterations in expression of insulin-like growth factors (IGFs) and the IGF binding proteins (IGFBPs) or may inhibit the protective effect of progestagens. Binding sites for IGF-1 and IGF-2 have been confirmed in both normal and malignant endometrium. Binding of IGF-1 is significantly higher in endometrial cancer compared to normal endometrium. In the Ishikawa human endometrial cancer cell line IGF-1 was a more potent mitogen than insulin or IGF-2. Insulin may increase mitogenicity by regulating the expression of IGFBPs. The IGFBPs are a family of proteins that have both proliferative and anti-proliferative effects. While all six high-affinity IGFBPs are expressed in the endometrium, IGFBP-1 is the best characterized. Hyperinsulinemia can decrease IGFBP-1 even in the presence of progesterone, perhaps inhibiting progesterone's protective effects. Interestingly, IGFBP-1 was undetectable or minimally expressed in endometrial cancers. Nestler discussed results of a 6-month treatment of 100 nonebese women with PCOS, which showed a somewhat greater effect of metformin than rosiglitazone and no benefit of administering both agents in combination. Long-term treatment with oral contraceptives decreases endometrial cancer, with a reduction in serum androgens and a decreases in hirsutism and acne, but may worsen insulin resistance and lead to deteriration in glucose tolerance. Insulin sensitizers, on the other hand, should decrease endometrial hyperplasia by inducing regular menses, but may not be as beneficial in improving androgen - related symptoms. Note that the Nurses Health Study (NHS) showed increased risk of diabetes in oral contraceptive users. These considerations may be related to the finding that women who used oral contraceptives have increased risk of myocardial infarction. Thus, in view of the particular increase in CVD risk among women with PCOS, one might be less likely to recommend oral contraceptives, while insulin sensitizers may be of particular benefit, decreasing androgens, improving ovulation and fertility, and reducing the risk of diabetes and CVD. Theoretically, metformin, a treatment which is now widely used to treat infertile women with PCOS, may have a role in preventing endometrial hyperstimulation by lowering insulin concentrations and restoring ovulation. However, the long-term effects of this drug in women with PCOS are not known and more studies are required before suggesting its use for preventing endometrial cancer.
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PMID:[Molecular action of insulin-sensitizing agents]. 1635 Jul 24

Studies in our laboratory and elsewhere have demonstrated numerous abnormalities of steroid and polypeptide hormone secretion in obesity: hyperestrogenemia and hypogonadotropic hypogonadism in obese men; diminished SHBG levels in both sexes; elevated free testosterone and free estradiol in obese women; PCOS-like gonadotropin and sex-hormone abnormalities in obese women; elevated serum insulin in both sexes; blunted stimulability of prolactin, growth hormone, and vasopressin in both sexes; and elevated basal levels and blunted stimulability and suppressibility of beta-endorphin in both sexes. All of these abnormalities have been clearly shown to be partly or completely reversible with weight loss, with the exception of the endorphin abnormalities. In that area, four out of the five studies reported show no reversibility with weight loss. Reversibility of nearly all the hormonal abnormalities of obesity (i.e., all but the hyperendorphinemia) by weight loss suggests that none of them is causative of obesity. Nevertheless, some of the reversible abnormalities may secondarily amplify the morbidity associated with obesity: the hyperinsulinemia may be related to the increased risk of hypertension, hyperlipidemia, coronary disease, and Type II diabetes; the elevated levels of free estradiol in obese women may be related to their increased risk of breast and endometrial cancer. The role of hyperendorphinemia in obesity clearly requires further investigation, since it is the only observed hormonal abnormality that appears to be non-reversible by weight loss, and also since there seems to be increased sensitivity to beta-endorphin in obesity. The possibility that endorphin abnormalities may be causal in obesity cannot be ruled out.
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PMID:A perspective on the hormonal abnormalities of obesity: are they cause or effect? 1635 9

Endometrial cancer is the most common gynecologic malignancy in the United States. Substantial epidemiologic data implicate an imbalance of estrogens and progestogens in the etiology of this disease. We propose that inflammation also plays a role in endometrial cancer development. Emerging laboratory data suggest that elevated levels of prostaglandin E(2) may underlie the transformation of normal endometrium to neoplastic tissue and that in vitro nonsteroidal anti-inflammatory drugs may inhibit endometrial cancer cell growth. In this review, we suggest that the risk factors for endometrial cancer--unopposed estrogens, anovulation, polycystic ovary syndrome, excessive menstruation, early menarche, and late menopause--may be viewed as factors increasing the exposure of the endometrium to inflammation, whereas pregnancy and smoking, two likely protective factors, have the opposite effect. Chronic inflammation can induce rapid cell division, increasing the possibility for replication error, ineffective DNA repair, and subsequent mutations. A proinflammatory milieu can also directly increase estrogen production. Hence, inflammation may work in conjunction with or in addition to estrogen exposure in the development of endometrial cancer.
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PMID:Inflammation and endometrial cancer: a hypothesis. 1636 98

The diagnostic criteria for polycystic ovary syndrome (PCOS) have recently been revised. The polycystic ovarian morphology has been introduced as part of the criteria and an international consensus has been achieved providing the basis for future research and collaboration. It is now accepted that polycystic ovary syndrome has important long-term health implications, including metabolic disorders and increased risk factors for cardiovascular disease. The overall risk of developing type 2 diabetes among women with PCOS was found to be increased 3-7 times. Women with PCOS have increased levels of cardiovascular risk factors: insulin resistance, obesity, dyslipidaemia, hypertension and markers of abnormal vascular function. However, the level of risk for cardiovascular disease remains uncertain. The limited epidemiological data available to date have shown no increase in cardiovascular events although the incidence of cerebrovascular events was increased. The evidence for an increased risk for endometrial carcinoma among women with PCOS is limited. Long-term epidemiological studies of women with well defined PCOS are needed in order to assess the risk of long-term health consequences, to identify the subgroups among PCOS women who need to be targeted and to determine the timing and nature of measures for intervention and prevention.
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PMID:Polycystic ovary syndrome. Revised diagnostic criteria and long-term health consequences. 1661 23

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy characterized by oligo/anovulatiaon and elevated circulating androgens or evidence of hyperandrogenism after all known potential causes have been excluded. In addition, insulin resistance and accompanying hyperinsulinemia commonly occur in women with PCOS. There is increasing evidence that the endocrinologic and metabolic abnormalities in PCOS may have complex effects on the endometrium, contributing to the infertility and endometrial disorders observed in women with this syndrome. Androgen receptors and steroid receptor co-activators are over-expressed in the endometrium of women with PCOS. Also, biomarkers of endometrial receptivity to embryonic implantation-such as alpha(v)beta3-integrin and glycodelin-are decreased, and epithelial expression of estrogen receptor alpha (ERalpha) abnormally persists in the window of implantation in endometrium in women with PCOS. In addition to being responsive to the steroid hormones estradiol, progesterone, and androgens, the endometrium is also a target for insulin, the receptor for which is cyclically regulated in normo-ovulatory women. In vitro, insulin inhibits the normal process of endometrial stromal differentiation (decidualization). In addition, insulin-like growth factors (IGFs) and their binding proteins are regulated in and act on endometrial cellular constituents, and hyperinsulinemia down-regulates hepatic IGFBP-1, resulting in elevated free IGF-I in the circulation. Thus, elevated estrogen (without the opposing effects of progesterone in the absence of ovulation), hyperinsulinemia, elevated free IGF-I and androgens, and obesity all likely contribute to endometrial dysfunction, infertility, increased miscarriage rate, endometrial hyperplasia, and endometrial cancer common in women with PCOS. The potential mechanisms underlying these disorders, specifically in women with PCOS, are complex and await additional transdisciplinary research for their complete elucidation.
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PMID:Endometrium in PCOS: Implantation and predisposition to endocrine CA. 1677 54

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in United States, affecting 6-10% of females in the reproductive age group. Recent studies have shown that insulin resistance plays an important role in the pathogenesis of PCOS. Traditionally, management of PCOS consisted mainly of ovulation induction, treatment of acne and hirsutism, and prevention of endometrial cancer. However, with mounting evidence showing that PCOS is associated with dysmetabolic syndrome and an increased risk for developing diabetes and heart disease, this can no longer be our sole focus. Current data support a strong recommendation that women with PCOS should undergo comprehensive evaluation for diabetes and recognized cardiovascular risk factors and receive appropriate treatment as needed. Lifestyle modifications remain the first-line therapy for all obese women with PCOS. However, many obese women with PCOS find weight loss difficult to achieve and maintain, and this is not an option for lean women with PCOS. For these reasons, insulin-sensitizing drugs are proving to be a promising and unique therapeutic option for chronic treatment of PCOS.
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PMID:Prevention of diabetes and cardiovascular disease in women with PCOS: treatment with insulin sensitizers. 1677 55

Polycystic ovary syndrome (PCOS) is the common endocrine disorder of reproductive age women which is characterized by hyperandrogenism, chronic anovulation, and increased risk for infertility, endometrial cancer, developing metabolic dysfunction (type II diabetes, dyslipidemia), hypertension and heart disease. The syndrome is also associated with some skin disorders: hirsutismus, alopecia androgenetica and acne. The successful dermatologic therapy requires the holistic diagnosis of the women with skin disorders described above and use the antiandrogenic treatment with conventional methods and laser depilation in hirsutismus. In this paper we present literature studies and our own experiences.
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PMID:[Polycystic ovary syndrome and hair unit function disturbances in dermatological practice]. 1742 3


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