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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

411 patients suffering from endometrial carcinoma were seen at the Roswell Park Memorial Institure in Buffalo, New York, between 1970 and 1978. These patients were matched and compared with 338 controls having no neoplastic disease or neoplasms other than of the female genital tract. There was a significantly higher incidence of diabetes, hypertension, and obesity in the uterine cancer patients than in the controls. On the other hand, nulliparity or family history of uterine or other cancer could not be correlated with endometrial cancer in these patients. The control and cancer groups did not differ markedly in the use of estrogens for menopausal or gynecologic reasons. Estrogen use in oral contraceptives (OCs) and for uncertain or unknown reasons was higher in the control than in the cancer group. The uterine cancer group was slightly older (median age 64.2) than the control group (median age 59.7), but this difference is small and believed unlikely to account for the results described.
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PMID:Estrogens and endometrial cancer. 694 29

Estrogen has been used to induce a wide variety of tumors in various animal species but only the rabbit is reported to reliably develop endometrial carcinoma. Variables associated in humans with an increase susceptibility to endometrial adenocarcinoma include aging, obesity, liver diseases, polycystic ovary disease, and ovarian tumors. In women estrogen induces mitotic activity in the endometrium and promotes the proliferation of the endometrium. Current concern that estrogen replacement therapy in postmenopausal women may be associated with increased risk of endometrial adenocarcinoma is based on: 1) reports of increased incidence of the disease, and 2) epidemiologic studies associating estrogen administration with an increased risk of endometrial carcinoma. The author draws the following conclusions based on the existing data: 1) there is likely a small but significant increase in the risk of development of endometrial adenocarcinoma among menopausal women on estrogen replacement therapy; 2) the increase in risk appears to be greatest for women who do not have any of the constitutional stigmas that would ordinarily place them at higher risk for adenocarcinoma; 3) risk increases with increasing duration of therapy, probably following a latent period of undetermined duration; 4) risk increases with increasing dose of estrogen; 5) progestin administration likely affords some protection against the risk, but the potential risks of administering the hormonal equivalent of a combination oral contraceptive periodically to elderly women have yet to be examined carefully; and 6) careful surveillance of patient populations on estrogen replacement therapy may limit the risk of adenocarcinoma associated with estrogens to early, highly curable lesions. It is incorrect to assume that estrogen actually causes carcinoma of the endometrium; it more likely induces a precancerous hyperplastic state in a dose-related fashion and only certain individuals ultimately develop invasive carcinoma.
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PMID:Does estrogen cause adenocarcinoma of the endometrium? 701 37

Clinical and pathologic findings were compared in 43 postmenopausal endometrial carcinoma patients who had received exogenous estrogens prior to diagnosis and 79 similar patients unexposed to estrogens. Estrogen non-users were more likely to manifest lower parity, later menopause, obesity, hypertension, and diabetes, all of which have been considered to be constitutional risk factors for the development of endometrial carcinoma. Although estrogen users and non-users had similar extent of disease as judged by clinical stage, there was a tendency to more myometrial invasion in hysterectomy specimens from non-users, as well as greater frequency of unfavorable histologic types and grades of tumor. At short-term follow-up, more recurrences occurred in non-users, and this tendency appeared to be independent of clinical stage, histologic type, histologic grade, or modality of treatment. The significance of these and other observation to the determination of the risk-benefit ratio for estrogen administration is discussed.
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PMID:Endometrial carcinoma: clinical-pathologic comparison of cases in postmenopausal women receiving and not receiving exogenous estrogens. 738 46

Elevated insulin concentrations are frequently found in both men and women with coronary heart disease (CHD), and are likely to be due to insulin resistance. Hyperinsulinaemia may increase CHD risk by directly promoting atherogenesis, and insulin propeptides may also be important in this respect. However, increased insulin concentrations may adversely affect several other CHD risk factors, and it has been postulated that insulin resistance is a pivotal metabolic disturbance in a constellation of CHD risk factors. There is an association between hyperinsulinaemia and hypertension, although it is not known if this association is direct. Increased insulin concentrations are also associated with high triglycerides, low HDL or HDL2 concentrations, and increased small dense LDL. Obesity is also associated with insulin resistance, and it is the central or android body fat distribution which correlates with these metabolic disturbances. All these associated factors constitute a distinct syndrome--the insulin resistance syndrome--which is a frequent finding in patients with CHD, including microvascular angina. It is possible that the adverse associations of insulin resistance and dyslipidaemia are mediated through increased nonesterified fatty acid flux. Increased insulin levels are also associated with increases in the anti-fibrinolytic factor, plasminogen activator inhibitor-I (PAI-I). Whilst increased insulin levels are typically associated with insulin resistance, reduced hepatic insulin uptake may also be important. We now have techniques which can quantitate insulin secretion, hepatic uptake and release, elimination, and resistance. The menopause has appreciable effect on insulin and glucose metabolism. Estrogen and progesterone augment pancreatic insulin secretion, but the former reduces insulin resistance whilst the latter increases it.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HRT mechanisms of action: carbohydrates. 819 41

The JCR:LA-cp rat exhibits an obese, insulin resistant, hyperlipidemic syndrome. Obese male rats, only, develop atherosclerosis and ischemic myocardial lesions. The obese males have a greater hyperinsulinemia, but the obese females have a much greater hypertriglyceridemia due to hypersecretion of very low density lipoprotein (VLDL). Obese rats of both sexes were surgically castrated at 6 weeks of age to study the influence of testosterone and estrogen secretion on the sexual dimorphism of metabolism and disease in this strain. Castration had no effect on body weight or food consumption up to 16 weeks of age. Castrated male rats had significantly improved glucose tolerance, but a doubled serum triglyceride concentration. Castrated female rats showed approximately halved triglyceride levels. The distribution of the triglyceride molecular species was altered in the castrated male rats to resemble that of the females in which there was no change with castration. The effects suggest that testosterone may inhibit hepatic triglyceride secretion and promotes insulin insensitivity. Estrogen appears to exacerbate hepatic hypersecretion of VLDL. Castration had no effect on myocardial lesion frequency in 9-month-old rats of either sex. This implies that estrogen does not exert a direct protective effect against cardiovascular disease in this animal model.
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PMID:Effect of castration on hyperlipidemic, insulin resistant JCR:LA-corpulent rats. 831 56

Widespread application of proven primary and secondary preventive strategies for coronary heart disease would result in substantial savings of life and health care dollars. Proven strategies (excluding lipid therapy) include quitting smoking, treating hypertension, physical activity, aspirin therapy, and appropriate use of anticoagulants, beta blockers, and angiotensin-converting enzyme inhibitors in survivors of myocardial infarction. Estrogen replacement therapy is currently under clinical investigation. Avoidance of obesity and tight control of diabetes are prudent interventions as yet unproved by clinical trials. Unfortunately, preventive strategies are frequently underutilized. The greatest challenge for preventive cardiology is to put into practice what we already know to prevent the development and progression of atherosclerosis.
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PMID:Nonlipid primary and secondary prevention strategies for coronary heart disease. 872 3

It has been suggested that there are two types of endometrial carcinoma: the first arises in younger women who have hyperestrogenism and has a favorable prognosis and the second occurs in older women, is not associated to estrogen stimulation, and has a poorer prognosis. This study examined the hypothesis that more aggressive carcinomas are found in older patients with no evidence of estrogen stimulation. A retrospective review of all patients (N = 82) with endometrial carcinoma diagnosed and treated at our institution between 1978 and 1990 was undertaken. The following data were analyzed: age at diagnosis, stage, race, histologic type, grade, depth of myometrial invasion, absence or presence of associated hyperplasia, and survival. The mean age of the patients was 64.8 years. Sixty (73%) of the 82 patients were considered estrogen-positive either because of obesity (body mass index > or = 27.3) or the use of unopposed exogenous estrogen. There were no statistically significant differences between estrogen-positive and estrogen-negative patients. Patients > or = 65 years had a 5-year survival of 60% compared with 74% for younger patients. There was a trend toward higher histologic grade among the older patients. Otherwise no statistically significant differences were found between these two groups. Estrogen-negative women > or = 65 years had the worst prognosis with a 5-year survival of 29%. As identified by other investigators, age at diagnosis is a significant indicator of prognosis in patients with endometrial carcinoma. In this series, thin, older (> or = 65 years) women who developed endometrial carcinoma had the worst prognosis.
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PMID:Poorer prognosis in older patients with endometrial adenocarcinoma. 877 67

Estrogen biosynthesis in adipose tissue increases with age and obesity, and has been implicated in the development of endometrial cancer and breast cancer. In normal human adipose tissue, expression of the CYP19 gene which encodes aromatase P450, the enzyme responsible for estrogen biosynthesis, is regulated by a distal promoter, namely promoter I.4. Stimulation of expression in adipose stromal cells by members of the type 1 cytokine family, i.e. interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF) and oncostatin M (OSM), is mediated via a Jak-STAT3 signaling pathway and a GAS element upstream of promoter I.4. In contrast, aromatase expression in breast adipose tissue proximal to tumor is increased three- to four-fold to the utilization of another promoter, namely promoter II, proximal to the translation initiation site. In the present report, we show that prostaglandin (PG) E2 is the most potent factor which stimulates aromatase expression via cyclic AMP and promoter II. PGE2 acts via EP1 and EP2 receptor subtypes to stimulate both the PKC and PKA pathways. The combined stimulation of both of these pathways results in the maximal expression of promoter II-specific CYP19 transcripts. Because PGE2 is a major secretory product both of breast tumor epithelial cells and fibroblasts, as well as of macrophages infiltrating the tumor site, then this could be the mechanism whereby estrogen biosynthesis is stimulated in breast sites adjacent to a tumor, leading in turn to increased growth and development of the tumor itself.
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PMID:Transcriptional regulation of CYP19 gene (aromatase) expression in adipose stromal cells in primary culture. 936 91

This article discusses the risk factors for coronary heart disease (CHD)--the leading cause of death in the US--in women. Studies have shown that cigarette smoking more than doubles CHD incidence and increases CHD mortality by 70%. A cohort study among more than 121,000 female nurses in the US revealed that the risk of CHD was 6 times greater in heavy smokers than nonsmokers. The level of blood cholesterol is also a strong risk factor for CHD: levels of high-density lipoprotein (HDL) cholesterol are inversely associated with the risk of CHD. Thus, lowering low-density lipoprotein (LDL) and increasing HDL cholesterol levels reduce CHD risk in both men and women. Hypertension is a risk factor which responds well to pharmacologic treatment, and increasing levels of physical activity were proven to decrease CHD risk in numerous studies. Meanwhile, obesity, which is prevalent in the US, worsens other coronary risk factors such as hypertension, diabetes, and hypercholesterolemia. A study showed that overweight women (body mass index values 29) are at 3 times the risk for CHD as those with body mass index values less than 21. Diabetes mellitus is another CHD risk factor which is stronger in women than in men, and CHD death rates are 3-7 times greater among diabetic than nondiabetic women. Other studies revealed that women who consumed alcohol in moderation (10-15 g of alcohol per day) had a 40% lower risk of CHD compared with nondrinkers. There is a significant relationship between combined oral contraceptive and cigarette use and increased risk of CHD. Estrogen replacement therapy, low-dose aspirin, and antioxidant vitamins have been proven in studies to reduce the risk of CHD in women.
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PMID:Risk factors for coronary heart disease in women. 950 75

Estrogen exerts a variety of effects not only on female reproductive organs but also on nonreproductive organs, including adipose tissue. Estrogen inhibits obesity triggered by ovariectomy in rodents. We studied the mechanism underlying this estrogen-dependent inhibition of obesity. Estrogen markedly decreased the amounts of fat accumulation and lipoprotein lipase (LPL) mRNA as well as triglyceride accumulation in genetically manipulated 3T3-L1 adipocytes stably expressing the estrogen receptor (ER). A pLPL(1980)-CAT construct, along with an ER expression vector, was introduced into differentiated 3T3-L1 cells, and CAT activities were determined. ER, mostly ligand-dependently, inhibited the basal LPL promoter activity by 7-fold. We searched the LPL promoter for an estrogen-responsive suppressive element by employing a set of 5'-deletion mutants of the pLPL-CAT reporter. Although there was no classical estrogen response element, it was demonstrated that an AP-1-like TGAATTC sequence located at (-1856/-1850) was responsible for the suppression of the LPL gene transcription by estrogen. An electrophoretic mobility shift assay probed with the TGAATTC sequence demonstrated formation of a specific DNA-nuclear protein complex. Interestingly, this complex was not affected by the addition of any antibodies against ER, c-Jun, c-Fos, JunB, or JunD. Because this TGAATTC element responded to phorbol ester and overexpression of CREB-binding protein abrogated the suppressive effect of estrogen on the LPL promoter, we conclude that a unique protein that is related to the AP-1 transcription factor families may be involved in the complex that binds to the TGAATTC element.
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PMID:Estrogen suppresses transcription of lipoprotein lipase gene. Existence of a unique estrogen response element on the lipoprotein lipase promoter. 1075 56


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