Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In most cases, the endometrioid adenocarcinoma of the endometrium is preceded by hyperplasia with different risk of progression into carcinoma. The original histologic slides from 560 consecutive cases with complex and atypical hyperplasia were re-examined to assess the interobserver-correlation. The hyperplasias were analyzed separately for their likelihood of progression to carcinoma in patients with and without progestogen hormonal therapy. In all cases, a fractional re-curreting was performed to establish the state of the disease. The leading symptom was vaginal bleeding in 65.5% of the cases in the postmenopausal period. Eighty-six percent of the patients presented with obesity (BMI > 30 kg/m(2)), 23% had had an exogeneous use of estrogens. Twenty-two cases were reclassified as simple hyperplasia and excluded from further analysis. The interobserver-correlation was 91% for complex, 92% for atypical hyperplasia, and 89% for endometrioid carcinoma, representing an overall correlation of 90%. Two percent of the cases with complex hyperplasia (8/390) progressed into carcinoma and 10.5% into atypical hyperplasia. Fifty-two percent of the atypical hyperplasias (58/112) progressed into carcinomas. In the case of progestogen treatment (n = 208; P < 0.0001) 61.5% showed remission confirmed by re-curetting, compared with 20.3% of the cases without hormonal treatment (n = 182; P < 0.0001). Endometrial hyperplasia without atypia is likely to respond to hormonal treatment. Especially in postmenopausal situation, atypical hyperplasia should be treated with total hysterectomy.
 ...
PMID:Risk of progression in complex and atypical endometrial hyperplasia: clinicopathologic analysis in cases with and without progestogen treatment. 1508 36

The majority of modern hormone replacement therapy (HRT) regimens contain estrogen and progestogens, given either in a cyclical or continuous manner. About 15% of the endometrial biopsies taken from women on sequential HRT show proliferative activity including atypical endometrial hyperplasia in up to 1% of the cases. The majority of biopsies from women under continuous combined HRT show an endometrial atrophy. About 2-3% of these women will present proliferative activity, usually without atypical hyperplasia. Contrary to breast cancer, an increased risk of endometrial cancer has not been reported in the WHI- and HERS-studies. However, endogenous factors, such as obesity, diabetes mellitus, the distribution of estrogen receptors alpha and beta and genetic polymorphisms for receptors and enzymes might alter the endometrial stimulation under different types of HRT. There should be a liberal indication for endometrial biopsies in Hereditary Non-Polyposis Colorectal Cancer (HNPCC). HNPCC-patients under HRT as well as for ultrasonographic evaluation of the endometrium. The risk of atypical hyperplasias or carcinoma under unopposed estrogen-therapy varies from 2 to 10%. So, this kind of HRT should not be used in non-hysterectomised women. As far as the risk of endometrial cancer under any kind of HRT is concerned, the different molecular pathways of endometrial carcinogenesis (type 1 and 2 cancers) should be taken into account. The use of tibolone leaves the endometrium unaffected.
 ...
PMID:Hormone replacement therapy (HRT) and endometrial morphology under consideration of the different molecular pathways in endometrial carcinogenesis. 1592 47

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.
 ...
PMID:[Molecular action of insulin-sensitizing agents]. 1635 Jul 24

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women on reproductive age. PCOS is characterized by the presence of anovulation, infertility and hyperandrogenism and is associated with obesity and insulin resistance. A major risk for neoplasms of the reproductive tract, like endometrial, breast and ovary cancer seems to be related to PCOS. While several studies have shown an increased risk for endometrial hyperplasia and cancer in PCOS patients, the variability of the selection criteria for PCOS has been recognized as a potential bias for these data. PCOS women also present clinical characteristics that are related to risk factors for breast cancer and some epidemiological evidences have been described on this issue. However, until now, a clear association between the presence of PCOS and breast carcinoma has yet not been found. Finally, high local steroid and growth factor concentrations are considered risk factors for ovary carcinoma, and are frequently observed in PCOS women. In turn, few studies have addressed the possibility of a link between PCOS and ovarian cancer and the results are conflicting but suggest that this association is unlikely.
 ...
PMID:[Polycystic ovary syndrome associated neoplasms]. 1644 64

Polycystic ovary syndrome (PCOS) is a syndrome, which can be defined as a group of recognisable patterns of symptoms or abnormalities that indicate a particular medical situation. The current definition of PCOS requires the presence of two of the following three conditions: (i) oligo- and/or anovulation; (ii) clinical and/or biochemical signs of hyperandrogenism; and (iii) polycystic ovaries--and the exclusion of other aetiologies. It is generally accepted that the prevalence of PCOS is approximately 5-10%, and that of polycystic ovaries alone is 21-23%. Other features of PCOS are obesity, insulin resistance, impaired glucose tolerance and type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease, obstructive sleep apnoea and infertility. An approach to a patient with possible PCOS should be directed towards making a diagnosis and screening for associated endocrine abnormalities. Therapeutic interventions are directed towards addressing the needs of the patient at present and towards preventing long-term complications of the syndrome. Body mass index, which is a primary mediator in the relationship between PCOS and health-related quality of life in obese PCOS adolescents, may play a similar role in other PCOS patients. Any intervention directed at reducing central obesity will not only improve quality of life but also correct hyperinsulinism and improve fertility and lipid and androgen profiles. It is also the only currently available intervention that can have a lifelong impact on reducing possible long-term complications of the syndrome. Lifestyle modification is the cardinal intervention. Pharmacological treatments are available for specific indications. Infertility can be treated with clomifene (clomiphene citrate), metformin, gonadotropins or surgery to the ovaries. Cyproterone (alone or in combination with ethinylestradiol) and spironolactone are the main drugs used in the treatment of hirsutism. Other drugs that can be considered include flutamide, ketoconazole and finasteride. Women with PCOS require ongoing surveillance to detect impaired glucose tolerance, hyperlipidaemia, endometrial hyperplasia and consequent complications. Obese women, in particular, require regular glucose tolerance testing because of the potential for rapid progression from normal to impaired glucose tolerance and diabetes. The focus of this article is the epidemiology, diagnosis and management of this common endocrine disorder. Diagnostic and co-morbid features are discussed separately to facilitate understanding of PCOS. Symptom-directed strategies, as well as short- and long-term goals of treatment, are outlined.
 ...
PMID:Diagnosis and management of polycystic ovary syndrome: a practical guide. 1674 5

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.
 ...
PMID:Endometrium in PCOS: Implantation and predisposition to endocrine CA. 1677 54

The aim of the study was to assess the feasibility and effect of treating atypical endometrial hyperplasia (AEH) with transcervical resection of endometrium (TCRE). Five cases of AEH incapable of hysterectomy for various reasons were treated with TCRE. All patients were followed up for 3-4 years postoperation to evaluate the thickness of endometrium, uterine cavity, and prognosis of the disease. All the patients provided informed consent for TCRE. In all five cases treated with TCRE, case 1 was for senility, hypertension, diabetes mellitus, and obesity; case 4 for senility, obsolete cerebral infarction, and hemiplegia; case 5 for uremia and chronic dysfunction of coagulation after renal transplantation; cases 2 and 3 for rejection of hysterectomy. All cases were followed up for more than 3 years after operation. Four had amenorrhea and one had dropping menses. The thickness of endometrium was no more than 5 mm in all the cases. TCRE is one available microinvasive surgery alternative to hysterectomy for AEH patients contraindicated to hysterectomy.
 ...
PMID:Management of abnormal uterine hemorrhage with atypical endometrial hyperplasia by transcervical resection of endometrium. 1680 56

Endometrial carcinoma is the most common malignant tumor of the female genitals in developed countries. The differences noted in epidemiology, presentation, and biological behaviors of endometrial carcinoma suggest that there are two fundamentally different pathogenic types of the disease: type I (estrogen related, endometrioid type) and type II (non-estrogen related, non-endometrioid type). The first type is more common and represents about two-thirds of cases. It occurs in women with hyperlipidemia, obesity, and signs of hyperestrogenism, including anovulatory uterine bleeding, infertility, late onset of menopause, ovarian stromal hyperplasia, and endometrial hyperplasia. The second type occurs in the absence of these features. Pathohistologically, type I tumors are composed of endometrioid carcinoma whereas type II tumors are composed of serous or clear cell carcinoma. Atypical hyperplasia is recognized as the precursor for the endometrioid type of endometrial carcinoma and endometrial intraepithelial carcinoma (EIC) as the precursor of serous carcinoma, the most common non-endometrioid type of endometrial carcinoma. In endometrioid type of endometrial carcinoma, it appears that PTEN mutation may be central to the initiation of endometrial proliferative lesions by which damage in other genes is then accumulated (e.g., DNA mismatch repair genes, K-ras, p53) in the progression to carcinoma. In contrast to endometrioid type, p53 mutations appear to be important in the conversion of atrophic endometrium to EIC and serous adenocarcinoma. Endometrial intraepithelial neoplasia (EIN) has been a recently defined precursor for the endometrioid type of endometrial carcinoma.
 ...
PMID:[Endometrial carcinoma and precursor lesions]. 1764 68

Routine sampling of the endometrium is not considered necessary in the investigation of female infertility in the presence of normal menstruation. We present the cases of five women diagnosed with endometrial pathology during the course of fertility investigations. Three women had atypical polypoid adenomyoma, one had complex endometrial hyperplasia and one had stage 1 endometrial adenocarcinoma. Only the latter described any abnormality in menstruation. No woman had polycystic ovarian syndrome nor any other reason in her history to suspect endometrial pathology. Two women had abnormal transvaginal ultrasound findings. Atypical polypoid adenomyoma is frequently associated with subfertility. Although usually biologically benign, malignant transformation has been reported. With current trends of increasing obesity and later age at attempted conception, the possibility of discovering endometrial pathology during fertility investigation is likely to increase. We believe that a thorough menstrual history and careful assessment of the endometrium is warranted in all women with fertility problems. A transvaginal pelvic ultrasound should be performed in the follicular (early) phase of the cycle. If this ultrasound examination and the woman's menstrual history are both normal, no further evaluation of the endometrial cavity is routinely required. Sonohysterography is superior to pelvic ultrasound in detecting intracavitary pathology and is thus recommended prior to IVF treatment. Hysteroscopy is the gold standard in the detection of intrauterine pathology and is well tolerated in the office setting. Where abnormality is suspected or detected at screening, futher investigation and concomitant treatment is essential. This is ideally performed via hysteroscopy with endometrial sampling or excision of focally abnormal areas.
 ...
PMID:Unsuspected endometrial pathology in the subfertile woman. 1772 23

Polycystic ovary syndrome (PCOS) is a complex, multifaceted, heterogeneous disorder that affects approximately 5 to 10% of women of reproductive age. It is characterized by hyperandrogenism, polycystic ovaries, and chronic anovulation along with insulin resistance, hyperinsulinemia, abdominal obesity, hypertension, and dyslipidemia as frequent metabolic traits (metabolic syndrome) that culminate in serious long-term consequences such as type 2 diabetes mellitus, endometrial hyperplasia, and coronary artery disease. It is one of the most common causes of anovulatory infertility. However, the heterogeneous clinical features of PCOS may change throughout the life span, starting from adolescence to postmenopausal age, largely influenced by obesity and metabolic alterations, and the phenotype of women with PCOS is variable, depending on the ethnic background. The etiology of PCOS is yet to be elucidated; however, it is believed that in utero fetal programming may have a significant role in the development of PCOS phenotype in adult life. Though a woman may be genetically predisposed to developing PCOS, it is only the interaction of environmental factors (obesity) with the genetic factors that results in the characteristic metabolic and menstrual disturbances and the final expression of the PCOS phenotype. Irrespective of geographic locations, a rapidly increasing prevalence of polycystic ovarian insulin resistance syndrome, excess body fat, adverse body fat patterning, hypertriglyceridemia, and obesity-related disease, such as diabetes and cardiovascular disease, have been reported in Asian Indians, suggesting that primary prevention strategies should be initiated early in this ethnic group. In lieu of the epidemic increase in the prevalence of obesity and diabetes mellitus in most industrialized countries including China and India owing to Westernization, urbanization, and mechanization, and evidence suggesting a pathogenetic role of obesity in the development of PCOS and related infertility, active intervention to combat the malice of these disorders is warranted. Pharmacologic therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals, and studies in China and India have proved to be effective.
 ...
PMID:Polycystic ovary syndrome in the Indian Subcontinent. 1818 Oct 79


<< Previous 1 2 3 4 5 6 7 8 Next >>