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

Diabetic women may have an increased risk of developing endometrial carcinoma. Ovarian and adrenal activity seem to be factors in the genesis of this cancer. We have measured serum sex hormone-binding globulin (SHBG), free and bound fractions of estrogens and androgens, and gonadotropins in 20 consecutive postmenopausal insulin-treated diabetic women and 16 normal postmenopausal women. The diabetics were nonketoacidotic, without nephropathy and without proliferative retinopathy. The groups were comparable regarding age and percent ideal body weight. The diabetic group had significantly increased serum levels of estrone (P less than 0.001), estrone sulfate (P less than 0.05), 17 beta-estradiol (P less than 0.02), and SHBG (P less than 0.001). Levels of testosterone, delta 4-androstenedione, and dehydroepiandrosterone sulfate tended to be higher (not significantly) in the diabetics. FSH and LH levels were similar in the two groups, while serum PRL was significantly lower in the diabetic group (P less than 0.02). The hormonal changes in the diabetics were not related to control of the diabetes. We conclude that total estrogen levels are increased in postmenopausal women with insulin-treated diabetes mellitus. High SHBG levels in these patients tend to keep the free fractions of sex hormones within normal limits.
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PMID:Androgens and estrogens in postmenopausal insulin-treated diabetic women. 267 38

It has been proposed that a nonsteroidal hormone such as insulin may directly exert an influence through estrogen receptors and alter the biologic behavior of steroid hormone target tissue. The implication of such a proposal is that diabetes may alter the outcome of estrogen receptor-positive tumors such as breast or endometrial carcinomas. To evaluate the effect of insulin on a receptor-positive tumor, we examined the direct effect of insulin on an estrogen receptor and its subsequent biologic effect on a receptor-positive endometrial carcinoma model in vitro and in vivo. An in vitro experiment demonstrated that when the estrogen receptor-positive cell line was grown in serum-free media with low insulin, there was a loss of intracellular receptors for estrogen. This loss of estrogen receptors was also associated with increased growth rate as reflected by increased thymidine uptake. Similarly, in vivo experiments demonstrated that a diabetic host with a high blood glucose level and a low insulin level exhibited development of growth of a receptor-negative tumor with accelerated growth rate in contrast to growth of a receptor-positive tumor with slower growth rate in a normal host with normal serum insulin and blood glucose levels. Data suggest that insulin may modulate the growth of estrogen receptor-positive tumors through its direct effect on estrogen receptors.
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PMID:Modulation of estrogen receptor by insulin and its biologic significance. 294 76

Ovarian secretion of testosterone and androstenedione is increased in postmenopausal women with endometrial cancer, and insulin stimulates ovarian stromal androgen synthesis in vitro. We undertook this study to investigate whether women with endometrial cancer have increased serum immunoreactive insulin levels. Ten postmenopausal women with endometrial carcinoma and 10 postmenopausal women without cancer who matched the cancer patients in age, years since menopause, and percentage of ideal body weight were studied. The women with endometrial cancer had significantly higher fasting serum insulin levels than the normal women [mean, 187 +/- 26 (+/- SE) vs. 55 +/- 11 pmol/L; P less than 0.01]. The cancer patients had significantly higher insulin responses after glucose administration than normal women (sum of 1, 2, and 3 h postglucose values, 5545 +/- 1526 vs. 1444 +/- 156 pmol/L; P less than 0.02), even though their glucose responses were similar. Nests of luteinized cells, which were positive for testosterone by immunoperoxidase staining, were found in the ovarian stroma of 8 of the women with endometrial cancer, but in only 1 of those without cancer (P less than 0.01). Specific high affinity insulin receptors were demonstrable in the stroma of the postmenopausal ovaries. These results suggest that the frequency of stromal luteinization is increased in women with endometrial cancer and that insulin may play a role in the pathogenesis of this luteinization.
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PMID:Hyperinsulinemia and stromal luteinization of the ovaries in postmenopausal women with endometrial cancer. 328 50

Plasma estrone (E1), 17 beta-estradiol (E2), delta 4-androstenedione (delta 4-A) and testosterone (T) levels in the peripheral vein were measured in 28 postmenopausal women with endometrial cancer and 19 control subjects without cancer matched to the cancer patients for age and weight. In the cancer patients, the mean +/- SD plasma E1, E2, delta 4-A and T levels were 53.0 +/- 29.0pg/ml, 31.3 +/- 28.9pg/ml, 1.92 +/- 0.96ng/ml and 0.71 +/- 0.24ng/ml, respectively. In the controls, the mean +/- SD plasma E1, E2, delta 4-A and T levels were 51.2 +/- 27.5pg/ml, 22.4 +/- 10.1 pg/ml, 1.70 +/- 0.6ng/ml and 0.84 +/- 0.24ng/ml, respectively. Similar concentrations were found in the control subjects. The correlation of each steroids with the percentage of ideal weight was examined. The percentage of ideal weight showed no correlation with E1, E2, delta 4-A and T in either group. Insulin response during glucose administration in the cancer patients was examined, and showed no correlation with each steroids. It was concluded that there is no differences between E1, E2, delta 4-A and T levels in cancer patients and control subjects matched to the cancer patients for age and weight. No correlation of insulin with ovarian steroid production was seen in the cancer patients.
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PMID:[Plasma concentration of estrogens and androgens in postmenopausal women with or without endometrial cancer]. 329 74

This review briefly outlines the pharmacology of natural and synthetic estrogens, and synthetic progestins, and summarizes their beneficial and adverse effects for contraceptive and menopausal therapy. Currently, oral contraceptives contain 30-50 mc synthetic estrogen, and 1-5 mg nor-progestin; menopausal therapy may be either 0.625-1.25 mg natural estrogen or estrogen plus 10 mg medroxyprogesterone acetate daily if the woman has her uterus. The biologic effects of estrogens are : decrease in lipoproteins, increased blood coagulation factors, increased blood pressure, decreased glucose tolerance. Progestins increase blood lipids and increase insulin and glucose. Oral contraceptives increase the risk of cardiovascular disease, particularly in smokers and in women over 35, in proportion to dose. These studies should be recapitulated in more detail with the newer low-dose pills. Orals have far more beneficial effects, besides providing an inexpensive, effective method contraception. The death rate of users of oral contraceptives is 3.7/100,000 (1.8 in nonsmokers and 6.5 in smokers), but the risk is 5.5 times higher in nonusers exposed to pregnancy and childbirth. The risk for users of barrier methods backed up by abortion is lower, but pills are cheaper and more acceptable. If woman did not take oral contraceptives, they would not be protected from cancer of the breast, ovary, endometrium, and ovarian and breast cysts. Menopausal therapy puts woman at increased risk of endometrial cancer only if the estrogen is taken alone, not if progestin is combined with the estrogen. There are no other adverse effects except decreased glucose tolerance and possible comprise of lipoproteins if a norprogestin of menopausal estrogens effectively treat hot flashes, depression, vaginal atrophy and bones loss.
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PMID:The adverse effects of hormonal therapy. 351 31

16 patients with carcinoma of the endometrium were treated with 50-mg medroxyprogesterone im twice daily for 1 year and studied to determine what effect this high dose of progesterone had on carbohydrate metabolism and liver function. Oral glucose tolerance values (fasting and 2 hour) were significantly elevated (p less than .001) at 12 and 18 months. Conjugated bilirubin was significantly elevated (p less than .01) at 18 months, aspartate aminotransferase was significantly elevated (p less than .001) at 12 and 18 months. Insulin values were raised transiently at 3 months. It is conluded that the changes in carbohydrate and liver function were small, appeared slowly, and included only a few pathologically elevated values; consequently the use of high-dose progestogen treatment for a 1-year period is considered safe.
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PMID:Effects of high-dose medroxyprogesterone treatment given for endometrial carcinoma on carbohydrate metabolism and liver function. 485 52

Seventeen women aged 55 to 76 years who had been treated for endometrial cancer by surgery or radiotherapy or a combination of both were given 300 mg of medroxyprogesterone acetate (MPA) daily by mouth. Before treatment and again during the 3rd week of treatment an oral glucose tolerance test (with measurement of serum insulin levels) and an ACTH-stimulation test were done. All blood glucose levels tended to be higher with MOA therapy and serum insulin levels were significantly increased 3 h after a glucose load. The rise of serum cortisol 30 min after ACTH-stimulation was significantly less with MPA therapy. Oral MPA thus appeared to have a glucocorticoid-like action.
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PMID:The influence of high doses of oral medroxyprogesterone acetate on glucose tolerance, serum insulin levels and adrenal response to ACTH. A study of 17 patients under treatment for endometrial cancer. 625 52

The insulin-like growth factor (IGF) system is thought to function as a mediator of steroid hormone actions in the endometrium. IGFs (IGF-I and IGF-II) are also potent mitogens in endometrial cancer. The biological actions of IGFs are modulated by specific binding proteins (IGFBP)--6 cloned and sequenced so far--which may either inhibit or enhance the effects of IGF at the cellular level. In the endometrium, IGFBP-1 gene expression is stimulated by progesterone and inhibited by insulin, while IGFBP-1 inhibits the mitogenic action of IGF-I. In this study, we used a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to investigate IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5 and IGFBP-6 gene expression in endometrial cancer tissues. Endometrial cancer tissue samples were collected from 20 women (aged 54-79 yrs) with stage I to II well-differentiated endometrial adenocarcinoma. Samples of normal endometrium (n = 14) obtained from women undergoing tubal ligation in various phases of the menstrual cycle, and normal early-pregnancy endometrium (decidua) were studied for comparison. In endometrial cancer tissues, the IGFBP-1 mRNA was undetectable or minimally expressed when studied by RT-PCR. The mean (+ SD) levels of IGFBP-2 and IGFBP-4 and IGFBP-5 mRNAs in endometrial cancer tissues did not differ from those in normal endometrium, in which no cyclic variation was observed, suggesting that the genes encoding IGFBP-2, IGFBP-4 and IGFBP-5 are not hormonally regulated in the endometrium. The IGFBP-6 mRNA expression showed a significant cyclic variation in normal endometrium, with low levels in late-proliferative and early- to mid-secretory phases and high expression in late-secretory and early-proliferative phases. In endometrial cancer tissues, the mean IGFBP-6 mRNA level was similar to that in cycling endometrium during the peri-ovulatory period. In summary, a continuous stimulation of the endometrial epithelial cells by IGFs with suppressed IGFBP-1 expression may lead to an imbalance in the IGF system of the endometrium and trigger an uncontrolled cell proliferation, ultimately resulting in malignant transformation.
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PMID:Suppressed expression of insulin-like growth factor binding protein-1 mRNA in the endometrium: a molecular mechanism associating endometrial cancer with its risk factors. 752 16

In uterine tissue, estrogen regulates various components of the insulin-like growth factor system; however, there are few suitable in vitro systems to examine these effects. Here we have examined the effects of 17-beta estradiol (E2) on expression and synthesis of insulin-like growth factors (IGF-I and IGF-II) and the insulin-like growth factor binding proteins (IGFBPs) by Ishikawa human endometrial cancer cells. Using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, we demonstrated that both E2 and 4-hydroxy-tamoxifen (OHT) enhanced IGF-I expression but had no effect on IGF-II expression. The pure antiestrogen ICI 182,780 had no effect on IGF-I expression and partially blocked the E2 and OHT effect on IGF-I expression. The effect of epidermal growth factor (EGF), which is able to mimic some of the effects of E2 in Ishikawa cells and uterine tissue, was also examined. EGF, unlike E2, did not increase IGF-I expression but rather resulted in a significant decrease in IGF-I messenger RNA (mRNA) levels. EGF also resulted in a small, nonsignificant increase in IGF-II mRNA levels. IGFBP-3, -5, and -6 mRNAs were detected by Northern blot analyses of Ishikawa cells RNA. However, only IGFBP-3 was consistently detected by ligand blotting of conditioned medium. E2 had no significant effect on expression of any of the binding proteins, whereas EGF increased IGFBP-5 mRNA levels. These data provide the first in vitro demonstration of regulation of IGF-I expression by E2. The Ishikawa cell line may provide a useful model to further investigate the molecular mechanisms underlying E2 regulation of IGF-I expression. Furthermore, we have demonstrated a clear dissociation of the effects of E2 and EGF on IGF-I expression in this cell line.
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PMID:Expression of insulin-like growth factors and their binding proteins in the estrogen responsive Ishikawa human endometrial cancer cell line. 752 33

Large-scale studies have demonstrated that obesity increases the risk of developing some forms of cancer. The association between obesity and cancer may result from factors such as fat distribution or sex hormone levels. Studies have also shown a relationship between a high-fat, low-fiber diet and cancer risk. High estrogen levels and low progesterone levels are associated with an increased risk of endometrial cancer. Obesity is known to raise estrogen levels and may lower progesterone levels. Obesity may increase the risk of breast cancer, but the evidence is less clear, since factors, such as age, country of origin, body-fat distribution, and family history, also play a major role in determining breast cancer risk. Sex hormones, insulin, and nutritional factors are also involved in the etiology of breast cancer. The incidence of lung cancer is inversely related to body weight.
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PMID:Obesity and cancer. 767 13


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