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

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

Oestrogen and progestin receptors are present in the cytosol and nuclear compartments of normal human endometrium, partly associated with their endogenous ligand hormones. Receptor concentrations fluctuate in relation to the menstrual cycle. Hyperplastic endometrium tends to contain high concentrations of cytosol progestin receptor, whereas the levels of cytosol and nuclear progestin receptors in endometrial adenocarcinoma are lower than in non-neoplastic endometrium. The receptor levels seem to decline with decreasing differentiation of the tumour. Progestin treatment extending over several weeks decreases cellular oestrogen and progestin receptor content in both hyperplastic and malignant endometria. Information based on small patient series suggests that patients suffering from advanced or recurrent endometrial carcinoma and having significant concentrations of both receptors in the tumour tend to have a more indolent clinical course than patients with absent or low tumour receptors. Patients whose lesions are progestin receptor-rich more frequently respond to progestin administration than those with receptor-poor tumours. In contrast, patients with advanced or recurrent disease after progestin treatment and with low tumour oestrogen and progestin receptor concentrations respond more often to combination cytotoxic chemotherapy than patients with higher tumour receptor levels. More data are needed about the clinical correlates of receptor determinations in human endometrial carcinoma to confirm these encouraging preliminary results, before the clinical significance of the determinations can be settled. since there are marked differences in the receptor concentrations reported by various investigators, possibly for methodological reasons, comparison of receptor data and treatment results from different groups is sometimes very difficult.
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PMID:Steroid receptors in normal, hyperplastic and malignant human endometria. 701 83

Biopsy specimens obtained from 150 women with primary, untreated endometrial carcinoma were investigated prospectively to determine the content of estrogen and progsterone receptors (E2 and PR). The investigation hoped to discover whether in vivo results of progesterone treatment of recurrent metastases correlated with in vitro occurrence of E2R and PR. At various intervals, 13 patients who had developed metastases despite routine surgical and radiation therapy were treated with gestagens (Depo-Provera or Proluton-Depot for 3-5 times weekly). 8 of the women, aged 61-71 years, proved E2R positive (greater than 10 fmol/mg of cytosolprotein), 2 had no PR, and the remaining 6 had PR concentrations from 7-892 fmol. 7 responded clinically to gestagen therapy (poorly differentiated tumors in 3 and moderately differetiated in 4). 5 of the cases (aged 50-84 years) were E2R negative; they had no PR, did not respond to gestagen therapy, and died after 2-8 months (2 poorly differentiated and 3 moderately). Therefore, hormone receptor tests in endometrial cancer do seem clinically predictive of outcome of gestagen treatment.
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PMID:Do estrogen and progesterone receptors (E2R and PR) in metastasizing endometrial cancers predict the response to gestagen therapy? 740 52

30 patients with advanced breast carcinoma, and 20 patients with advanced endometrial carcinoma were treated with high doses, 500 mg./day, of MPA (medroxyprogesterone acetate) administered orally for 3 months. Evaluation of results showed responses in only 30% of women treated, independently of the type of carcinoma. In the breast carcinoma group median duration of response was 10 months, and median survival time 15 months; in the second group of patients median duration of response was 15 months, and median survival time was not yet reached after 28 months of follow-up. Negative side effects were gain of body weight and hypertension; oral MPA administration seems to have a lower response rate than parenteral administration; it is, however, easier to handle, and could present a useful alternative in maintenance therapy.
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PMID:[Oral high doses of medroxyprogesterone acetate (MPA) in the treatment of advanced phases of breast and endometrial cancer]. 745 90

Endometrial fibroblasts derived from uterine endometrium as controls and endometrial cancer cells (Ishikawa and HHUA cells) were used to analyze the manner of induction of c-Ha-ras transcripts in endometrial cancers, some of which are estrogen-dependent in growth. Estrogen increased c-Ha-ras expression and tyrosine kinase (TK) activity in fibroblast and Ishikawa cells, but not in HHUA cells. Progesterone diminished c-Ha-ras expression and tyrosine kinase (TK) activity induced by estradiol in the fibroblasts, but not in Ishikawa cells, which persistently overexpressed c-Ha-ras. In these cells, epidermal growth factor (EGF) increased c-Ha-ras expression as did estradiol. Pretreatment with tyrphostin, an inhibitor of TK, abolished estrogen-inducible overexpression of c-Ha-ras. The combination of both estradiol and EGF at maximum effective concentration exerted no additive or synergistic effect on induction of c-Ha-ras expression. In conclusion, persistent activation of TK might lead to overexpression of c-Ha-ras in some endometrial cancer cells under estrogen predominant milieu, which might be associated with the transformation or growth potential.
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PMID:Estrogen induces c-Ha-ras expression via activation of tyrosine kinase in uterine endometrial fibroblasts and cancer cells. 757 18

In recent years, we treated recurrent uterine endometrial cancer by combined therapy including CDDP. But in poor cases, like renal failure and such, it is difficult to perform the therapy. Two cases of recurrent uterine endometrial cancer treated earlier with MPA were presently treated with an addition of etoposide. The first case was given etoposide (50 mg/m2/day 4 times for 21 days by oral administration). The target tumor mass was reduced in size, occult blood vanished, and the tumor marker was reduced. The other case was treated with etoposide, 50 mg/body/day for 21 days by oral administration, but because of diarrhea, the dose had to be decreased to 25 mg/body/day every day. The tumor marker was reduced and genital bleeding vanished. These cases suggested that etoposide-MPA combined therapy might be effective for recurrent uterine endometrial cancer of well-differentiated type.
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PMID:[Treatment of recurrent uterine endometrial cancer in adjuvant therapy with medroxyprogesterone acetate (MPA) in addition of etoposide]. 782 70


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