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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

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

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

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

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

The selection of contraception for women over the age of 35 presents significant problems. The popular IUD is often contraindicated on account of producing pathological cervical and/or uterine changes. In such women the suitable contraceptives are pure gestagen pills and injectables (Depo-Provera and norethindrone enanthate). Depo-Provera contains the active ingredient medroxyprogesterone acetate (DMPA), which imitates the activity of endogenic progesterone and increases the activity of 17-hydroxyprogesterone 6- or 7-fold. Its mechanism of action on the uterine epithelium consists of antiestrogenic and antiandrogenic activity. In 1995 approximately 3.5 million women were using DMPA. Its contraceptive effectiveness amounts to 0-1.2 pregnancies per 100 women in the course of 1 year. In a 1987 multi-centered trial it was observed that the use of 250 and 500 mg of DMPA every 9 months produced a higher incidence of pregnancy than the use of 150 mg every 3 months. The causes of discontinuation of DMPA use are irregular bleeding (10.5%), reduction of libido (1.6%), and weight gain (1.4%). A 1984 clinical study of 3905 women showed that 54% of them had no untoward effects while using DMPA. The frequency of development of amenorrhea with DMPA use varies from 8% to 72%. Its hematological parameters are good and some studies showed that DMPA does not increase the risk of development of cancer of the endometrium, ovaries, and cervix. A 1991 study suggests that the relative risk of breast cancer may increase after 4 years of use of DMPA in women under 35, however, according to a 1994 study, above this age the risk is minimal. DMPA use lowers the risk of endometrial cancer, and this protective effect lasts for 8 years after cessation of use. Higher doses of DMPA treat endometrial cancer. After halting DMPA use the average time for conception to occur is 5.5 months. DMPA use in the first trimester does not produce adverse effects on the newborn or on lactation.
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PMID:[Contraception with injectable long-acting preparation depo-provera]. 765 32

Mortality is the greatest concern in assessing risks of modern reversible contraception. The problems identified with older oral contraceptives (OCs) have decreased with the lower doses in current OCs. These problems include cardiovascular and thrombotic effects, changes in lipid metabolism, breast cancer, liver cancer, increased risk of chlamydia cervicitis, no protection against sexually transmitted diseases (STDs) and HIV, and interferes with breast feeding. On the other hand, OCs protect against anemia, menstrual disorders, ectopic pregnancy, acute pelvic inflammatory disease (PID), and ovarian and endometrial cancer. Since the contraceptive implant, Norplant, has no estrogens, it does not have the cardiovascular risks associated with OCs. Possible risks from Norplant use include changes in carbohydrate, liver, and lipid metabolism but they tend to be clinically insignificant and no protection against STDs/HIV. Menstruation disorders are the major side effect. Apparent benefits of Norplant are protection against anemia and ectopic pregnancy and no effect on lactation. The injectable contraceptive, Depo-Provera, causes menstrual changes, may slightly increase the risk of breast cancer, may decrease bone density, and does not protect against STDs/HIV. It protects against endometrial cancer. It has no effect on metabolism. Risks associated with the IUD include PID, perforation, anemia, increased menstrual bleeding, and pregnancy. IUDs do not affect the quantity of composition of breast milk. They are best suited for women in a mutually monogamous, long-term relationship. Barrier methods provide some degree of protection against STDs/HIV and PID. Condoms provide the most protection. They do not affect lactation. Their major complications are contraceptive failure and risks associated with pregnancy. For all women, especially those in high risk categories, one must balance the risks of modern contraceptive use with the risks of childbearing and with their benefits.
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PMID:The safety of modern contraceptives. 784 6

The major complaint about injectable hormonal contraceptives, e.g., Depo-Provera (DMPA), is changes in menstrual patterns. In fact, menstrual alterations are the leading reasons women opt to discontinue their use. Injectables' ability to suppress ovulation over a long period and to cause extended endometrial atrophy can delay a return to fertility. Prior to 1967, clinicians used DMPA to treat endometrial cancer. In 1967, its manufacture, Upjohn, requested the Food and Drug Administration's (FDA) permission to expand its use as a contraceptive. FDA wanted more clinical data because it was concerned about its effect on future fertility. It also requested animal studies on DMPA's effect on bone deposition and cancer risk. By 1978, there was so much evidence of increase risk of cervical and breast cancer in animal models and of birth defects that FDA decided not to approve DMPA. Upjohn had exhausted all options by 1986. WHO clinical research (conducted in Kenya, Mexico, and Thailand) revealed in 1991 that DMPA was not a carcinogen. In fact, DMPA users had a significantly lower risk of endometrial cancer than women who did not use DMPA. Clinical research in Thailand suggested that DMPA causes an increased risk of low birth weight and neonatal mortality. A case-control study in New Zealand indicated that DMPA users experienced more bond density loss than non-DMPA users. Nevertheless, FDA approved DMPA as a contraceptive in October 1992. It did order Upjohn to do a postmarket study of DMPA's effect on bone density and risk of osteoporosis, however. Despite its approval, the controversies would continue until further research provided more details about cancer and other risks. Before January 1993, Upjohn sold vials of DMPA to clinicians at $11 to $12 per injection. After January 1993, it began selling it in single-dose disposable syringes at a cost of $29.50. When the cost of a clinic visit is added, the cost per DMPA injection increases to about $50 ($200/year).
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PMID:Injectable hormones and regulatory controversy: an end to the long-running story? 843 75

A prospective study was devised in 1980 to assess the effect on survival of neoadjuvant Provera as part of the primary treatment of endometrial carcinoma in conjunction with surgery and radiotherapy. Between June 1980 and June 1985, 218 patients with Stage I adenocarcinoma of the corpus uteri were allocated on the basis of hospital of presentation to receive either neoadjuvant treatment with medroxyprogesterone acetate (MPA) 100 mg t.i.d. p.o. from diagnosis for 90 days, or no adjuvant treatment (the control group). The minimum follow-up was 5 years. There was no significant difference between the overall actuarial survival in the treatment group (123 cases) and that in the control group (95 cases). This was 83.7% and 69.2% at 5 and 10 years respectively in the treatment group and 78.9% and 70.7% in the control group (P > 0.1).
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PMID:Stage I endometrial carcinoma: the role of neoadjuvant progesterone therapy. 848 58


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