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

In response to a recent report (Fam Plann Perspect 11: 47, 1979) that two of 12 rhesus monkeys given 50 times the human dose of depot medroxyprogesterone acetate (DMPA), by body weight, for ten years had developed endometrial carcinoma (CA), a retrospective survey of all hospital admissions for proven endometrial CA in two Thai provinces where DMPA contraceptive injections have been widely used since 1965 was made. From 1974 through 1978, 16 women were hospitalized with confirmed diagnoses of endometrial CA. None of the nine women successfully followed up had previously used oral or injectable contraceptives, nor has the recorded incidence of endometrial CA increased in these provinces. Base on the available evidence, the authors conclude that (a) the data on monkeys given very large doses of DMPA for ten years do not apply to women given normal doses of DMPA for prolonged periods and (b) widespread and long-term use of DMPA can and should be continued.
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PMID:International forum update: depot medroxyprogesterone acetate and endometrial carcinoma. 4 91

Many scientists have criticized the mandatory use of dogs for studies of the chronic toxicity of synthetic steroidal contraceptive hormones. The estimated annual incidence rates for cancer of all sites in dogs is 381.2/100,000 dogs. The estimated relative risk (R) value for the occurrence of tumors in the Beagle breed is 0.9; for malignant tumors, the R value in the Beagle is 0.8. A review of the hormonal potency of various contraceptive steroids in the Beagles indicates that progestogenic compounds generally produce a much lower progestational activity in dogs than in women, and the the predominant hormonal action of norethisterone in dogs is estrogenicity rather than progestogenicity. This weak activity for the canine species may account for some of the toxicological findings for norethisterone and related compounds in the Beagle. It is also possible that there are species differences in the relative affinities of estrogen and progesterone receptors for contraceptive steroids. Studies on long-term administration to female Beagle dogs suggest that the nodules found in the mammary gland are not histologically comparable to mammary tumors found in the human female although there is a superficial morphological resemblance to some forms of human mammary dysplasia. Several authors suggest that the results of testing progestational compounds in Beagles are unlikely to be indicative of a potential hazard to the human female. In testing megestrol acetate, it is suggested that the unique sensitivity of the canine females to megestrol acetate is exemplified by intense mammary development at dose levels 10 times the human oral contraceptive level. In contrast, daily dose levels of 500 mg/day in women as a palliative for endometrial cancer have been used with no serious side effects or mammary enlargement. Also the canine mammary gland produces certain pathological changes following administration of natural or synthetic progesterones in a way not readily seen in other species. Possible alternative models (cat, pig) for contraceptive steroid toxicological studies and recommendations for future research are discussed.
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PMID:Contraceptive steroid toxicology in the Beagle dog and its relevance to human carcinogenicity. 6 32

A proportion of cancers in endocrine target tissues can show the presence of specific receptors for either steroid or polypetide hormones. Manipulation of the controlling hormones does not guarantee regression. A third of cancers in endocrine target organs (breast, uterine endometrium, and prostate) show a 50% reduction in size of lesions after hormonal therapy. If regression resulting from an aggressive form of therapy lasts a short while and the tumor reactivates by the time the unpleasant effects of the therapy wear off, the treatment is not palliative. Endocrine therapy in prostatic cancer is palliative but there is no evidence that is increases survival. 11 different progestational agents in endometrial cancer therapy in the past 25 years resulted in a 30-35% response. Response must be maintained by continual treatment and may last from 12 months to 7-8 years. In breast cancer, tumors with a significant level of estrogen receptor (ER+) have about a 60% chance of regression vs. tumors without estrogen receptors (ER-), 10%. Advanced cancers of the thyroid of the papillary or follicular type regress when the patient is treated by thyroxine, .3 mg daily. Leukemia and lymphoma are frequently treated, with varying degrees of success with corticosteroid therapy, which may also predispose the patient to intercurrent infection. Renal cancer has been often treated by medroxyprogesterone acetate or testosterone propionate, with little success.
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PMID:Endocrine therapy in cancer. 8 86

The use of medroxyprogesterone acetate (MPA) was incorporated into a nuclear receptor assay for progestin receptor in human endometrium. The assay was developed because MPA is a better ligand than progesterone since it does not bind to corticosteroid-binding globulin and gives greater kinetic stability to the nuclear complex. The MPA nuclear receptor complex for malignant endometrium dissociated at a faster rate than did the complex obtained from normal endometrium, an alteration in binding kinetics which could not be explained by instability of the receptors from malignant endometrium. Factors, including radiation therapy, plasma proteins, endogenous steroids, receptor degradation, tissue heterogeneity, and limited sample size, which influence the interpretation of receptor assay were systematically evaluated. In spite of these controls, it would be premature to conclude that the clinical observations indicate altered receptor from malignant tissue. Further studies are required on endometrial carcinoma which is free of normal tissue fragments. Clinically, nuclear receptor levels were highest in normal endometrium but decreased in samples of malignant endometrium as tumors became more anaplastic. The lowest nuclear binding activity was detected in samples of metastatic endometrial tissue (carcinoma). Hopefully, this nuclear receptor assay (which uses MPA because its dissociation was slower than progesterone) will provide data for correlating clinical response to therapy.
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PMID:Nuclear progestin receptors in normal and malignant human endometrium. 42 86

A radioimmunoassay to quantitate ethinylestradiol (EE-2) in both plasma and endometrium is described. In 29 women receiving sequential oral contraceptive (OC) therapy (chlormadinone acetate, 2 mg plus mestranol, 80 mcg) for 6-84 months, a single blood sample and a single endometrial sample were simultaneously obtained on different days of the pseudomenstrual cycle. In 24 women under 40 years of age, the mean plasma EE-2 concentrations were similar during the 1st (989 +/- 94 pg/ml) and the 2nd half of the cycle (1053 +/- 186 pg/ml) (P . 0.05). A similar finding was observed with regard to mean endometrial EE-2 concentrations (3.55 +/- 2.1 and 5.89 +/- 1.7 mcg/gm or wet tissue, respectively). On the other hand, 5 women over 40 years of age had plasma EE-2 concentrations similar to those of the previous group, but the mean endometrial EE-2 concentration was 0.9 +/- 0.6 mcg/gm of wet tissue (P .05). Although plasma follicle stimulating hormone and luteinizing hormone did not show midcycle peak values, complete suppression of both gonadotropins was not observed. These results show that endometrium has a great ability to concentrate EE-2, and this ability seems to be greater in women below age 40 than above. Whether or not this observation might be related to the known higher incidence of endometrial cancer in women less than 40 years old who have been under chronic sequential OC therapy cannot be disclosed from this limited number of determinations. Future study might uncover competitive effects between synthetic steroids and endogenous hormones in the endometrium.
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PMID:Accumulation of ethinylestradiol in blood and endometrium of women taking oral contraceptives: the sequential therapy. 49 82

The effects of high doses of medroxyprogesterone acetate (MPA) on liver metabolism were investigated by determining the plasma antipyrine clearance rates for a group of 11 patients with endometrial cancer both before and during use of MPA in therapy. MPA dosage was 250 mg, intramuscularly, for 6 days. The antipyrine half-life was prolonged in 4 patients. MPA treatment had an inducing effect on antipyrine metabolism; the plasma half-life of the drug was shortened and apparent clearance rate increased; however, no change occurred in the apparent volume of distribution of the drug. Significant decreases in bilirubin were also seen (P .01), but no other liver function tests showed significant differences. When the patients were divided into 2 groups according to age over or under 60 years, there was a significant difference (P .05), with the younger group having a half-life of 8.1 hours and the older group evincing a half-life of 13.6. These half-lives were reduced by MPA treatment to 7.5 and 11 hours, respectively. The results indicate that MPA therapy has an inducing effect on hepatic enzyme activity and antipyrine metabolism.
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PMID:Antipyrine metabolism and liver function in patients treated with high-dose medroxyprogesterone. 50 96

The results obtained by treating 137 patients suffering from advanced carcinoma of the endometrium with medroxyprogesterone acetate (MPA) at a hospital in Rome, Italy, are reported. 48 cases were treated wtih 250 mg of MPA twice weekly for 3 months, followed by a long-term treatment with 250 mg weekly; later 89 cases were treated with 500 mg twice weekly for 3 months, followed by a long-term treatment with 500 mg weekly. Positive results were obtained in 20.8% of the cases in the 1st group and in 41.5% of the cases in the 2nd, which shows the greater effectiveness of the larger doses. Side effects mainly included asthma, skin rashes, and jaundice symptoms, which could be treated; it was always possible to continue the MPA treatment. Results appeared to be better in the case of patients with a localized disease, while the age of the patient appeared to be unrelated to the effectiveness of treatment. The survival time of the patients who responded to MPA treatment was markedly longer, the average being 2 years.
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PMID:[Treatment with progestational agents in the advanced phase of carcinoma of the endometrium. Study of 137 patients treated at the 1st division of obstetrics and gynecology of the San Camillo De Lellis Hospital in Rome]. 77 77

High dosage gestagen therapy is indicated for progressive endometrial carcinomas when there are recurring or metastasizing tumors or the presence of extensive tumors suggesting incomplete surgical removal. Both norethisterone acetate in dosages of 20-30 mg die and hydroxyprogesterone capronate in dosages of 1-5 gm weekly are well tolerated. Interruption of medication is to be avoided, since recurrences have been noted even after discontinuation of successful long-term therapy. In 60-70% of the patients, general and localized improvements were observed. A hemostatic effect usually occurred during the 1st week of treatment. Avoidance of local recurrence and an average survival period of 34 months after detection of lung metastasis as well as cases of complete remission speak highly for the therapy. Low dosage, short-term progesterone treatment for all cases of endometrial carcinoma is not recommended at the present time.
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PMID:[Results of high dosage progesterone therapy in carcinoma corporis uteri]. 86 63

Diabetes and obesity were noted in 21.3% and 42.3% respectively of 94 patients with adenocarcinoma corporis uteri. Hypertension and ovarian or mammary neoplasia were also common. Obese and diabetic subjects proved more sensitive to treatment with high doses of medroxyprogesterone acetate. Screening for precancerous states or carcinoma of the endometrium in obese and diabetic women is suggested.
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PMID:[Diabetes, obesity and adenocarcinoma of corpus uteri]. 99 85

The withdrawal from the market of the oral contraceptives Volidan 21 and Serial 28 was based on work in beagle dogs treated for 7 years with high doses of megestrol acetate. The treated animals developed significantly more tumors than untreated controls. Chlormadinone acetate was withdrawn from clinical use in 1970 on the basis of similar reports. All other progestogens in use in Britain had no effect on the incidence of tumors. The only neoplasm linked with oral contraceptives by clinical evidence is hepatic adenoma. In menopausal and postmenopausal patients estrogen therapy may increase the risk of endometrial uterine cancer. For most young women oral contraception is a compromise between safety and reliability. Serious thromboembolic complications increase with age, cigarette smoking, and hypertension. Patients should be screened for the presence of risk factors and the effects of treatment regularly assessed. In menopausal women, regular monitoring for endometrial cancer is advised. Medical supervision of hormone therapy is needed.
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PMID:Editorial: Cancer risks from hormone treatment. 120 97


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