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

The authors studied electron microscopically the effect of a large dose of medroxyprogesterone acetate (Depo-Provera) on the fine structure of endometrial carcinoma, with special regard to the annulate lamellae of the cells. Following treatment in one-third of their cases of highly-differentiated endometrial carcinoma the glandular epithelial cells were found to show a marked regression. After using a large dose of progestogen, the oestrogen-dependent annulate lamellae 'disappeared' from the cytoplasm of the cells. This phenomenon may be one of the morphological manifestations of subcellular oestrogen-progesterone antagonism.
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PMID:Effect of progestogen (Depo-Provera) on annulate lamellae in endometrial carcinoma. 624 Aug 79

A review is given of the comparative pathology of endometrial carcinomas regarding the incidence, the morphology, and the relation with endometrial hyperplasia. Compared to man, endometrial carcinomas in animals are fairly rare, except in rabbits, in cattle, and in a stock of Han: Wistar rats. In rabbits the endometrial carcinomas are mostly primary multiple and present in both horns. Histologically they are almost always adenocarcinomas. The histological structure can vary considerably with regard to the degree of differentiation. In cattle the endometrial carcinomas are mostly singular. Histologically they are mostly adenocarcinomas, often accompanied by formation of much dense fibrous tissue. In rats the endometrial carcinomas are mostly primary multiple adenocarcinomas. In man as well as in the rabbit and in the rat, relationships have been described between endometrial hyperplasia and endometrial carcinoma. It is striking that in the dog, a species in which endometrial hyperplasia very often occurs, endometrial carcinomas should be rare. The endometrial carcinoma in the rabbit as an animal model for human endometrial carcinoma is discussed extensively. In both species there are signs indicating relationships between endometrial carcinomas and sex hormones, especially oestrogens. The incidence in rabbits is very high. Endometrial carcinomas in rabbits can be transplanted subcutaneously in the same rabbit. They can also be cultured in vitro. Moreover the rabbit is a suitable species to study the progesterone/progesterone-receptor complex by determining the synthesis of the progesterone-induced protein uteroglobin which may be important in studying endometrial carcinomas. Uteroglobin is a good marker for a functional 'Progesterone-PR-DNA-mRNAug-Uteroglobin- System' (or PUG-System).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative pathology of endometrial carcinoma. 638 39

Currently Depo-Provera has not been approved by the FDA (Food and Drug Administration) for contraceptive use in the U.S., although USAID is allowed to distribute it for use in population programs in developing countries. The FDA denied Upjohn's petition for approval of the basis of tests showing that Depo-Provera has caused an increased incidence of mammary carcinoma in laboratory dogs. A review of additional tests conducted on laboratory animals, the results of which were not released to the public, indicates that adverse results were withheld from the public by the manufacturer. Tests with laboratory dogs and monkeys have revealed many serious side effects from the drug. Endometrial carcinoma, shortened life expectancy, interference with carbohydrate metabolism, and suppression of immune responses are the most major of these side effects. The immunosuppressive effects make women more vulnerable to infection and also seem to promote malignancy. Exposure to Depo-Provera, as to other progestogens, in utero is associated with an increased risk of congenital malformation in children. In view of the seriousness of the findings, questions are raised as to the advisability of continued contraceptive use of Depo-Provera.
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PMID:Depo-Provera: a critical analysis. 645 87

The sex steroid hormone receptor levels of uterine cytosol were assayed in the course of experimental induction of endometrial carcinoma in rats. Effects of administration of various hormones on the receptor levels were examined with each histological pattern of endometrium. 1) The dissociation constants for E2 and R5020 bindings with uterine cytosol were almost fixed in spite of various histological patterns of endometrium. 2) The influence of administrated hormones on the receptor assay system could be neglected by the preincubation of uterine cytosol with DCC for five times. 3) By the administration of DES for six weeks, estrogen receptor levels were increased significantly in adenocarcinoma, while progesterone receptor levels did not show the tendency of decreasing. 4) By the administration of MPA combined with DES, estrogen receptor levels were not decreased significantly in both atypical adenomatous hyperplasia and adenocarcinoma; progesterone receptor levels were decreased in all groups. 5) By the administration of MPA, estrogen receptor levels were decreased significantly in adenocarcinoma. These data suggest that receptor levels can be controlled by the administration of sex hormones in the course of development of endometrial carcinoma.
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PMID:[Changes of sex steroid hormone receptors in rat uterine cytosol during experimental induction of endometrial carcinoma (author's transl)]. 645 22

In this discussion of Depo-Provera (DMPA) attention is directed to the following: pharmacology and mode of action; clinical considerations; cervical dysplasia; breast cancer; and endometrial carcinoma. DMPA, a microcrystalline suspension of medroxy-progesterone acetate, is used widely around the world as a contraceptive, particularly in developing countries. MPA (medroxy-progesterone acetate) is a synthetic progesterone which in its mycrocrystalline depot form can be delivered by simple intramuscular injection or jet injector to that depending on the dose administered plateau contraceptive blood levels will be maintained for 90-180 days when doses of 150 mg and 300 mg respectively are used. The effect of DMPA in suppressing ovulation is at the hypothalmic level where it inhibits the gonadotrophic release responsible for the midcycle surge in luteinizing hormone responsible for ovulation. When 150 mg is administered every 3 months pregnancy rates range from 0.0-1.2/100 women years. The pregnancy rates range from 0.0-3.8/100 women years when 300 mg is administered every 6 months. The drug is usually administered initially in the first 7 days of the menstrual cycle to avoid possible effects on an established pregnancy. Menstrual disturbances are the major reason for discontinuation of DMPA. The usual side effects are amenorrhea, irregular but infrequent bleeding, and a few instances of prolonged or heavy bleeding. There is no evidence to suggest that DMPA increases the risk of invasive cancer of the cervix, but the evidence regarding the incidence of cervical dysplasia is ambiguous. There have not been any cases of breast cancer that can be related to DMPA use, but DMPA toxicology studies on beagle bitches revealed an increased incidence of benign and malignant breast tumors. It is well established that in adenocarcinoma of the endometrium DMPA is effective in causing regression and preventing recurrence of this tumor.
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PMID:Depo provera in perspective. 646 84

In a long-term study (1 year) the plasma concentration of medroxyprogesterone acetate (MPA, Depo-Provera, Provera, Upjohn) was measured in 30 patients with endometrial carcinoma treated with MPA in the following dosages: 1) MPA 1 000 mg i.m. weekly; 2) MPA 1 000 mg i.m. once every second week, and; 3) MPA 100 mg orally twice daily. In the orally treated group the blood samples were taken just before the next tablet. The plasma concentration in the orally treated group rapidly reached steady state, while the i.m. treated group showed gradually increasing levels that had a tendency to level off after 6 months. The mean concentration at the end of the year was about three times higher for MPA 1000 mg i.m. weekly than for MPA 100 mg orally twice daily. This does not take into consideration the peak MPA level that occurs 2-4 hours after each tablet. MPA i.m. has a very good depot effect, with release of MPA from the injection site for up to 9 months. The steady initial increase in MPA plasma concentration seen in the i.m. treated groups is probably due to the additions of new depots rather than accumulation in the body generally.
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PMID:Medroxyprogesterone acetate (MPA) plasma levels after oral and intramuscular administration in a long-term study. 679 91

The effect of high dose medroxyprogesterone (MPA) on serum lipids was studied in 31 postmenopausal patients with endometrial cancer. After 3 months of MPA treatment, total cholesterol decreased by 18% (P less than 0.001), LDL cholesterol by 16% (P less than 0.01) and HDL cholesterol by 38% (P less than 0.001) from the respective pretreatment values; correspondingly, the ratio of HDL to total cholesterol decreased (P less than 0.001). Similar changes were found as early as 2 weeks after start of treatment. In the 15 controls receiving no progestin treatment, full dose intracavitary radiotherapy and gynecological surgery had no effect on these serum lipids.
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PMID:Effect of high dose progestin on serum lipids. 687 Sep 84

The objective of the present phase II trial was to analyze the efficacy of the antiestrogen tamoxifen in advanced endometrial carcinoma. 32 patients with measurable disease entered the study and were treated with tamoxifen 10 mg 3 times daily. Among 26 patients with evaluable disease remission (partial and complete) was achieved in 8 (30%), no change in 7 (27%) and progressive disease in 11 (42%). Duration of response was significantly longer in 4 patients with complete remission (30.5 + months) compared to patients with partial remission and no change. No correlation was found between response to treatment with tamoxifen and disease free interval but a favourable connection was observed between good response and low grade of anaplasia of the tumor. 9 of the patients had received prior treatment with MPA. No complete cross resistance or cross sensitivity between MPA and tamoxifen was apparent.
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PMID:Tamoxifen treatment of advanced endometrial carcinoma. A phase II study. 687 94

Receptors for steroid hormones are necessary for hormonal action. All tissues which are targets for hormonal action contain receptors. Estrogens seem to be required to induce progesterone receptor. Progesterone, in turn, has been shown to lower the level of estradiol receptors in the endometria of normal women. This would be likely to prevent the development of endometrial hyperplasia, a known precursor of endometrial cancer. Progesterones are, thus, related to endometrial cancer as both antagonists of estrogens and as therapeutic agents.
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PMID:Sex steroid receptors in endometrial hyperplasia and neoplasia [proceedings]. 693 74

In Canada depot medroxyprogesterone acetate (DMPA) (Depo-Provera, Upjohn Company of Canada) has been cleared for use in the management of endometriosis in the nonpregnant woman and for palliation of advanced endometrial cancer. There remains some question as to whether physicians are authorized to use this drug for other clinical conditions. The health protection branch of the Department of National Health and Welfare, after a review of the world literature and data on the clinical use of this drug for indications other than those mentioned, has concluded that the available clinical experience with DMPA shows a favorable risk/benefit ratio and that the drug does not present an undue health hazard. Since the 1st clinical studies began in the early 1960s experience with DMPA for contraception has totalled more than 10 million women years. It is estimated that over 1.2 million women in various countries are currently using DMPA for contraception and that several thousand women have used it for 10 years or longer. Available data indicate that the risk/benefit ratio for DMPA in a appropriately selected population is as favorable as that for oral contraceptives (OCs) or IUDs. These statements have been supported by many international organizations concerned with family planning. The special advisory committee on reproductive physiology of the health protection branch reviewed the October 1981 publication concerning the use of DMPA in the Ontario government facilities for the mentally retarded. Its authors considered "of borderline significance" the finding of 3 deaths from carcinoma of the breast in 533 women treated with DMPA at some time during their lives. The evidence for a causal relationship was very tenuous. The composition of the study cohort and the control group as well as the incomplete data collection made the statistical evaluation questionable. Also the higher prevalence of carcinoma of the breast in mentally retarded individuals and in patients with epilepsy and the fact that the other medications many of these patients must have taken were not reported or commented upon further confuse the issue and invalidate the inferences. From a review of the world literature it was learned that among 11,500 DMPA users in the US there have been only 4 reported cases of carcinoma of the breast, for a rate that is lower than that expected in a Canadian control population. The committee reaffirms its opinion tha DMPA is safe in the management of specific clinical problems. It is believed that there is no undue health hazard when DMPA is used to produce amenorrhea in physically or mentally handicapped individuals unable to cope satisfactorily with menstrual hygiene.
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PMID:Should depot medroxyprogesterone acetate be considered for additional uses? 713 35


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