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

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

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

A prospective clinical trial using combination chemotherapy consisting of cyclophosphamide, doxorubicin, cis-Platinum and megestrol acetate (CAP-M) was initiated to study its effect on advanced or recurrent endometrial adenocarcinoma. Fifteen patients were clinically evaluable. Nine patients (60%) demonstrated an overall objective clinical response resulting in either complete regression of disease (33%) or a reduction in tumor size. For all responders the mean progression free interval was eight months, with a range of five to 11 months. Similarly, a mean survival time of 12 months with a range of five to 21 months was observed. An additional four patients showed no progressive disease for a mean of seven months duration. Reversible cis-Platinum-induced nephrotoxicity occurred in two patients. This is the first reported series of endometrial cancer patients using nonhormonal cytotoxic agents, including cis-Platinum, in conjunction with a progestin. This preliminary experience is encouraging and appears worthy of further clinical evaluation.
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PMID:Treatment of advanced or recurrent endometrial adenocarcinoma with cyclophosphamide, doxorubicin, cis-Platinum, and megestrol acetate. 653 27

In vitro responsiveness of endometrial adenocarcinoma to progestins was evaluated histologically by incubation of tissue fragments in medium containing 10(-6) M medroxyprogesterone acetate. In a series of 19 experiments, formation of sub- and supranuclear vacuoles, which reflects accumulation of glycogen in response to medroxyprogesterone acetate added to the medium, was observed in well-preserved glandular epithelial cells only when the level of cytosolic progesterone receptor was above 300 fmol/mg protein. Previously, we have reported similar results obtained in in vivo experiments. The present findings suggest that simple organ culture and histological procedures can be used to identify specimens of endometrial cancer that have functional progesterone receptors and are capable of responding to progestins. They also indicate that levels of progesterone receptor required to obtain responses to progestins are considerably higher than those necessary for analytical detection and that therefore the quantity and not merely the detectability of progesterone receptors must be taken into consideration for the prediction of responses to progestins. In addition, in vitro responses to progestins may indicate the presence in endometrial cancer tissue of functional estrogen receptors and potential responsiveness to antiestrogens, since estrogen stimulation appears to be needed for the synthesis of progesterone receptors.
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PMID:Histological evaluation of in vitro responses of endometrial adenocarcinoma to progestins and their relation to progesterone receptor levels. 669 40

A double-blind cross-over study was performed on 21 patients treated for endometrial carcinomas who had severe menopausal symptoms. The patients were randomized into two groups and received medroxyprogesterone acetate (MPA) 100 mg twice daily per os for 12 weeks and a placebo for 12 weeks. A significantly better effect on hot flushes and sweating was obtained with MPA than with the placebo. On average the maximum effect was achieved by MPA after 4-6 weeks. Six patients had a weight gain of more than 3 kg during the MPA administration, compared with none during the placebo administration. No significant difference was found in the blood pressure increase above 160/90 mmHg between MPA and placebo groups. Patients with endometrial carcinoma may risk exacerbation of their disease by undergoing therapy with exogenous estrogen. In contrast, MPA has been found of value in the treatment of disseminated endometrial carcinomas. In this study oral MPA was effective in the treatment of vasomotor menopausal symptoms and may be an alternative in women for whom estrogens might be hazardous.
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PMID:Effect of oral medroxyprogesterone acetate on menopausal symptoms in patients with endometrial carcinoma. 676 Jun 53

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

A patient with endometrial carcinoma metastatic to the groin has had serial cytosol estrogen (ERc) and progestin (PRc) receptor determinations during hormonal therapy. The primary lesion was well differentiated and a left iliac node metastasis had high ERc and borderline PRc levels. PRc levels increased substantially in a subsequently appearing right groin metastasis at three times during the clinical course when the patient was treated with the antiestrogen tamoxifen. The patient had a partial response to the first course of tamoxifen and at one later time briefly had stabilized disease on tamoxifen plus medroxyprogesterone acetate. Tamoxifen with and without progestin should be further evaluated in the treatment of endometrial carcinoma.
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PMID:Tamoxifen-induced increase in cytosol progestin receptor levels in a case of metastatic endometrial cancer. 688 30

Estradiol dehydrogenase (E2DH) is a well-known progesterone-dependent enzyme in human endometrium, and its induction has been proposed as a means to test hormonal sensitivity of endometrial carcinoma. While administration of progestins to some patients with endometrial carcinoma resulted in increased endometrial E2DH activity, efforts to induce this enzyme, in vitro, in these tumors have been unsuccessful. The reasons for such failure were investigated in the present study. Progesterone receptor (PR) concentrations and E2DH activities were simultaneously measured in proliferative and malignant endometria under organ culture conditions. Cytoplasmic PR concentrations were determined by Scatchard plot analysis of [3H]progesterone binding in fresh samples and in tissue explants incubated in nutrient medium at 37 degrees in a humidified 5% CO2 atmosphere for various periods of time. Parallel incubations of explants with and without 500 ng medroxyprogesterone acetate per ml were carried out for monitoring E2DH induction. In proliferative endometrium, the progesterone-specific binding sites remained stable during the culture periods, and the E2DH activities were stimulated severalfold by medroxyprogesterone acetate. In contrast, the PR concentrations in carcinoma explants were undetectable after a 24-hr period, and this was associated with a lack of increase in E2DH activity. These findings provide evidence that progestin-induced endometrial E2DH activity is a receptor-mediated phenomenon. In addition, these results demonstrate clearly that the ineffectiveness of progestin to induce E2DH in endometrial cancer specimens, in vitro, is related to the instability of PR under culture conditions. It is suggested that any experiment designed to follow effects of steroids on target tissues must take into account the stability of steroid receptors under in vitro conditions.
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PMID:Failure of progestins to induce estradiol dehydrogenase activity in endometrial carcinoma, in vitro. 694 38

Treatment of menopausal symptoms with a combination of natural oestrogens (17beta-oestradiol and oestriol) and a gestagen (norethisterone acetate), given continuously without interruption, has been found to have a good effect on menopausal symptoms, at the same time as the endometrium is maintained or brought to an atrophic state. This method seems to be a new approach to oestrogenic therapy, and in spite of the inconvenience of rather frequent--though as a rule very slight--bleeding during the first months of treatment, it should be of value. After 3-4 mth of treatment bleeding practically never occurs and the endometrium almost invariably becomes completely atrophic. It would seem that this might imply a lowered risk of development of endometrial cancer. A series of 265 patients treated in accordance with this principle for up to more and than 4 yr is presented.
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PMID:Continuous treatment with natural oestrogens and progestogens. A method to avoid endometrial stimulation. 702 79

For patients with severe vasomotor flushes who require therapy but for whom estrogens are contraindicated, progestins can be tried. These drugs appear to offer the benefit of a reduction of vasomotor flushes without such unwanted side effects as the increased risk of contracting endometrial cancer. However, progestins cannot replace estrogens universally since there is no evidence that they prove effective against osteoporosis-related fractures and genital atrophy. Nonetheless, as more physicians begin to add medroxyprogesterone acetate to the estrogen regimen to reduce the risk of endometrial hyperplasia, it might be that a lower dose of estrogen will be necessary to relieve flushes. We hope that this additive effect exists, although it has not yet been shown. Whether or not the addition of medroxyprogesterone will carry risks or counteract the beneficial effects of estrogens on such disorders as osteoporosis remains to be elucidated. What is clear from the medroxyprogesterone and estrogen studies is that whenever these drugs are discontinued, the vasomotor flushes can recur, albeit with less intensity and less frequency.
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PMID:The effects of progestins on vasomotor flushes. 713 42


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