Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among 30-40 year old women, 40% of pregnancies are unplanned, which is indicative of the unreliability of the birth control methods they are using. The 1992 Ortho Birth Control Study interviewed almost 7000 women, of whom 8% listed withdrawal and 4% listed the rhythm method. These two methods have failure rates of 24% and 19%, respectively. Birth control methods often disappoint the users and increasingly they turn to sterilization. 48% of married women aged 15-44 had themselves been sterilized or had a sterilized partner in the Ortho survey. Although reversal of tubal ligation succeeds in 43-88% of cases, conception cannot be guaranteed. For women over the age of 30 who are healthy and do not smoke, low-estrogen or no-estrogen oral contraceptive pills are considered safe. Taking the pill also helps prevent ovarian and endometrial cancer. The failure rate is 6%. Barrier methods also offer protection from sexually transmitted diseases including HIV. Condoms are favored by 33% of unmarried women and 19% of married women. Sexually active 40-44 year old unmarried women run a 14-19% risk of contracting a sexually transmitted disease (STD) in a 12-month period. Diaphragms offer some protection against STDs, but their failure rate is 18%. IUDs are regaining popularity, but only 1% of women use them (ParaGard T380A or Progestasert). Pelvic inflammatory disease is the reason: a 1992 study showed that 0.97% of women developed it within 20 days of use. Norplant is a long-term implant containing levonorgestrel with a failure rate of 0.5%. A 1993 study followed 1253 implant users over 12 months and found a very low rate of pregnancy, but 75% experienced some side effects during the first year. About half of the women using Norplant removed it after 2.5 years because of irregular bleeding. Depo-Provera is an injectable administered every 3 months, but after removal it can take up to a year for ovulation to return. Side effects may include hair loss and weight gain; and links to breast cancer have also been suggested.
 ...
PMID:Birth control over 30. 1229 85

The McCormick Hospital's Family Planning program in Chiang Mai, Thailand surveyed all admissions to the hospital for carcinoma of the endometrium in light of the discovery by the Upjohn Company that 2 monkeys had developed endometrial carcinoma when given 50x the dosage of Depo-Provera. Chiang Mai and Lumpoon provinces were the targets of this survey since these are the 2 areas where Depo-Provera was widely used and where 35,000 women were current users. 16 of the 25 recorded cases hailed from these 2 provinces and 6 were eliminated from this examination. There has been no increase in the recorded incidence of endometrial carcinoma despite the widespread use of Depo-Provera (a total of 86,511 women; 864,492 injections; usage experience of 207,694 women-years; and more than 300 women who have been using the drug for 10-13 years). In 1978, there was actually a lower recorded incidence than in the 3 years prior. Thus the Upjohn data (using 50x the human dosage level for 10 years) should not be applied to women on normal doses of Depo-Provera. Also, long-term use of these injections can be continued without concern about developing endometrial carcinoma.
 ...
PMID:Endometrial carcinoma survey in Thailand. 1230 18

The members of the International Planned Parenthood Federation's recently formed Medical Advisory Panel met in London in October 1980 and discussed recent findings relevant to the controversial injectable contraceptive, Depo-Provera. After reviewing the evidence the panel endorsed the continued use of Depo-Provera but recognized that careful long term investigation of all types of contraceptive methods were needed. The specific conclusions reached by the members were 1) the high rate of death associated with pregnancy and illegal abortion in many developing countries, justifies the continued use of Depo-Provera; 2) monkey studies in which 2 out of 16 monkeys treated with Depo-Provera developed endometrial cancer were considered to be statistically insignifant findings; 3) there was no evidence linking the contraceptive with cervical cancer; 4) human studies show no evidence of a relationship between breast cancer and the use of Depo-Provera; 5) the results of beagle studies in which a relationship between Depo-Provera and breast cancer was observed are not applicable to humans since dogs and humans metabolize progestational steroids differently; 6) Depo-Provera may increase the amount and duration of lactation; 7) only a small fraction of the contraceptive is absorbed into the system of infants breast-fed by mothers who take Depo-Provera and follow-up studies in Chile and Mexico failed to detect any adverse effect of Depo-Provera on the infants; 8) the effects on the fetuses of women who received the injection while pregnant is unknown; 9) weight gain is the only known metabolic effect associated with the injection; 10) serious menstrual disorders among Depo-Provera users are rare; 12) the contraceptive does not appear to cause subsequent infertility.
 ...
PMID:Injectable contraception. 1231 87

FDA has approved medroxyprogesterone acetate as Depo Provera Contraceptive Injection, effective for 3 months in preventing pregnancy in women. In clinical studies, the drug's failure rate was less than 1%. However, physicians must ensure that patients receive injections on schedule to prevent pregnancy. The recommended dose is 150 mg administered every 3 months by deep, intramuscular injection in the gluteal or deltoid muscle. Most women in clinical studies of Depo Provera experienced menstrual irregularities. As use continued, amenorrhea became common, reported by 57% of the women by the end of a year of treatment. Other side effects included weight gain, headache, nervousness, abdominal pain or discomfort, dizziness, and asthenia. Physicians should administer the drug only to women found not to be pregnant, because fetal exposure may lead to low birth weight and other problems. Recent data have demonstrated that longterm use may contribute to osteoporosis, and the drug's manufacturer, the Upjohn Company of Kalamazoo, Michigan, will conduct additional research to study this possible side effect. Contraindications are similar to those for other contraceptives and include undiagnosed vaginal bleeding, known or suspected malignancy of breast, thromboembolic disorders, cerebral vascular disease, and liver dysfunction. Depo Provera was developed in the 1960s and has been approved for contraception in many other countries. When FDA first reviewed data on the drug in the 1970s, animal studies raised questions about its potential to cause breast cancer. Since then, longterm controlled clinical studies in other countries have shown a risk of breast cancer comparable to oral contraceptives, and no increased risk for ovarian, liver, or cervical cancer. The studies also showed that the contraceptive injection reduced the risk of endometrial cancer. FDA approved the drug October 29, 1992.
 ...
PMID:3-month contraceptive injection approved. 1231 15

Depo-Provera, the Upjohn Company's trade name for depo-medroxy-progesterone acetate (DMPA), is a progestin which is presently approved by the Food and Drug Administration (FDA) for the treatment of endometrial cancer. Clinical trials of DMPA as an injectable contraceptive were initiated in 1963, and many trials continue to be conducted abroad at the request of foreign governments. The contraceptive regimen consists of 150 mg administered intramuscularly every 3 months. DMPA has twice been denied FDA approval as a contraceptive in the United States, despite the advice of FDA advisory committees. The most recent evidence concerning the effectiveness and complications of DMPA as a contraceptive comes from 5000-8000 users in clinical trials at Atlanta's Emory/Grady Family Planning Program and from 86,511 users in Chiang Mai and Lumpoon provinces in Thailand. Contraceptive failure rates were 0.26 pregnancies/100 woman years of use in Atlanta and 1.2 pregnancies/100 woman years of use in Thailand. A recent study of breast cancer found that women who used DMPA had no increased risk of developing breast cancer within the 12 year followup period. In another study it was found that estrogen supplementation was given during only 0.2% of the total 15,615 woman-months of DMPA use. Further, it was found that when DMPA was available for contraception, it was chosen by 11.5% of patients desiring contraception. This was 2nd only to oral contraceptives in frequency as a method choice. Regarding counseling patients who ask about DMPA, private physicians retain the discretionary ability to prescribe FDA-approved drugs for indications other than those for which the drugs are approved. Although there is little hard evidence in support of denial of approval, approval is questionable because drug approval has become more of a political than a scientific process in the United States.
 ...
PMID:Researcher explains status of Depo Provera. [Answer to question of Marienetta Blackwell]. 1233 40

Controversy still surrounds the use of the injectable contraceptive, Depo-Provera, in 3rd world countries, when it has yet to be approved in the US, Canada, Japan, and other developed nations. Some medical professionals maintain Depo is both safe and effective and could curb rapid population growth worldwide. With no conclusive decision made, some countries have approved Depo while others have not yet decided. Originally approved for a variety of uses, Depo is approved in the US only as a treatment for advanced endometrial cancer; however, it is now available in 65 countries and is used as a contraceptive in the Philippines. Depo and its companion Norigest are both progestonogenic injectables and were developed in the late 1950s. Injectables inhibit ovulation and thicken cervical mucus, thereby preventing fertilization. The reservoir usually lasts from 3-6 months, and its action cannot be reversed until the body has completely absorbed the drug. Injectables are highly effective; most accidental pregnancies occur shortly after the 1st injection before the drug has taken effect or at the end of an interval when its effect is wearing off. Overall the rate of fertility return corresponds to the rates for the pill and the IUD. Injectables have the advantage of preventing side effects brought on by estrogens; thus they would be beneficial to women desiring to use contraception but who cannot manage pill side effects. They do not interfere with lactation and have the lowest failure rate of the reversible methods. Important to developing countries is that injectables require no effort on the part of the user. Injectables do disrupt the menstrual pattern and Depo use often results in weight gain. Little is known about the longterm risks of Depo; however, in 1973 the US Food and Drug Administration withdrew approval of Depo for pregnancy-related uses because of links to birth defects. Other recent studies have uncovered other possible effects including uncertainty about whether injectables affect the composition of breastmilk or whether they raise blood glucose levels. Ethics have entered into the controversy with the "contraceptive double standard" where Depo has been exported to 3rd world nations when it has been ruled unsafe for American women. Campaigns have been organized against the distribution and use of injectables in the developed nations and a few in the 3rd world have begun to organize. While the Philippines has approved Depo, it is not yet considered an official method of the National Population Program. Policymakers await a more thorough analysis of factors for and against the promotion of the drug.
 ...
PMID:Injectable contraceptives: how safe are they? 1233 24

In October 1992, the US Food and Drug Administration (FDA) approved Depo-Provera for contraceptive use thus increasing the number of available contraceptives to women. Yet USAID has distributed it through its family planning programs in developing countries for many years. It has been available in the US since 1969 for noncontraceptive purposes such as endometrial cancer treatment. More than 30 million women around the world have used it to prevent conception. Today about 9 million women in 90 countries use it. A reason FDA did not approve Depo-Provera is that some studies revealed a link between it and breast tumors and cervical cancer in animals. More recent research conducted by WHO shows no connection with cervical cancer or ovarian cancer. In fact, it demonstrates Depo-Provera may protect against endometrial cancer. Yet it does indicate an insignificant increased risk of breast cancer in younger women. Some research suggests Depo-Provera may decrease bone density leading to osteoporosis and may increase the risk of having a low birth weight infant if the child is conceived before an injection. Evidence exists that it may lead to longer delays in becoming pregnant than other forms of contraception. Still 70% do conceive within 12 months after the last injection. Each Depo-Provera injection delivers a progestin in a water-based solution over 12 weeks resulting in suppressed ovulation. Its failure rate is .5%/year, so Depo-Provera is one of the most effective reversible contraceptive available. The most common side effects are menstrual changes and weight gain (5-15 lbs.). Some contraindications include pregnancy, heart or liver disease, and breast cancer. As of November 1992, the FDA had not announced the cost or whether there would be a reduced price for family planning and public health clinics. Women's health and rights advocates plan on monitoring introduction of Depo-Provera to make sure that women have received comprehensive information and were not coerced to use it.
 ...
PMID:FDA gives final approval to Depo amid concerns over safety, cost and coercion. 1234 20

Depot medroxyprogesterone acetate (DMPA, Depo-Provera) is used for contraception by 8-9 million women in more than 90 countries, including the US, as of January 1993. Pharmacologically active levels of DMPA persist for 3-4 months following injection. A 150 mg dose is used most often for high contraceptive efficacy every 3 months. Norethindrone enanthate (NET-EN, Noristerat) is somewhat less widely used and is not marketed in the US. Injectables act primarily by inhibiting ovulation, lowering the levels of follicle-stimulating hormone and luteinizing hormone. Approximately 50% of women using DMPA for 1 year report amenorrhea whose occurrence is less frequent with NET-EN. Menstrual changes are the most frequent causes of discontinuation of injectables. In cases of heavy bleeding it is appropriate to undergo gynecological examination to rule out unrelated conditions, such as vaginitis, cervicitis, or cervical lesions. The use of conjugated estrogen (12.5-2.5 mg daily) for 10-21 days will minimize bleeding. Some women using injectables experience headache, dizziness, bloating of the abdomen or breast, and mood changes. Long-term use of DMPA or NET-EN can often result in 1-3 kg weight gain. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives was launched in 1979 to examine cancer risks with the use of DMPA in Thailand, Mexico, and Kenya. The relative risk of breast cancer was 1.21, which was statistically not significant. In women diagnosed with breast cancer under age 35, short-term exposure to DMPA was associated with a slightly increased breast cancer risk, which, however, was not associated with duration of use. DMPA dramatically lowers the risk of endometrial cancer for at least eight years following discontinuation of its use. DMPA did not alter the risk of cervical cancer. Fertility returns in 70% of former users within 12 months; it is suitable for postpartum and lactating women, and provides other noncontraceptive benefits.
 ...
PMID:Injectable contraception: the USA perspective. 1234 20

To study the functional differences between the two progesterone receptor isoforms (hPRA and hPRB) in human endometrial cancer, two new endometrial carcinoma cell lines were created-one expressing hPRA and one expressing hPRB.A well-differentiated, hPR-negative Ishikawa cell line was stably transfected with either hPRA or hPRB cDNA. Transfected cells were selected, and two cell lines expressing approximately equal amounts of receptor were isolated-one expressing hPRA (PRA-14) and one expressing hPRB (PRB-59). Cell growth experiments revealed a growth-inhibitory response to progestins (MPA and R5020) in the PRB-59 cells but not in the PRA-14 cells. Differences in expression of genes targeted by the two isoforms were studied using a cDNA expression array technique. A different set of genes appeared to be progesterone regulated in the PRA-14 cells than in the PRB-59 cells. None of the genes were regulated by both hPRA and hPRB. Insulin-like growth factor binding protein 3 expression was studied in more detail as an example of a gene regulated in PRB-59 cells but not in PRA-14 cells. We established a new model to study functional differences between the two hPR isoforms in human endometrial carcinoma cells. This model revealed distinctive differences in target gene regulation between the two hPR isoforms. Moreover, antiproliferative actions of progesterone on human endometrial cancer cells could be observed only in the PRB-expressing cell line.
 ...
PMID:Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines. 1251 94

Carcinoma of the endometrium is the most common female pelvic malignancy in the US. Although it is primarily a disease of the postmenopausal female, 25% of patients are premenopausal, with 3-5% in women 40 years old or younger. The younger group of women with endometrial carcinoma are frequently nulligravid with a history of infertility, and a strong desire to preserve fertility. This may pose a therapeutic dilemma for both patients and treating physicians. Medical treatment for young patients with grade 1 endometrial carcinoma who wish to preserve fertility is a reasonable and appealing option. A comprehensive evaluation prior to counseling the patient should include. A complete history and physical examination. A formal D&C with review of histology with an experienced gyn-onc pathologist. Evaluation of the pelvic and abdomen preferably with contrast-enhanced MRI or transvaginal ultrasound. In patients found to have a clinical stage I grade 1 tumor and who want to preserve fertility, thorough counseling including risks and benefits, and explanation that the data is partial and incomplete due to the lack of appropriate controlled studies is mandatory. In patients considered for medical treatment, a high dose progestin regimen should be started with endometrial sampling every 3 months until complete regression of the tumor is documented. For patients willing to conceive at this stage, treatment options should be discussed. In women who do not want pregnancy at this stage, a maintenance treatment with oral contraceptive agent or Depo-provera (medroxyprogesterone acetate 150 mg i.m. q 12 weeks) should be recommended, with periodic ultrasound evaluation of the endometrium. When the patient finishes her fertility plans, the option of hysterectomy should be considered. Although most responses are long standing, there is a small risk of progression during or after cessation of progestin therapy.
 ...
PMID:Endometrial adenocarcinoma in young patients: evaluation and fertility-preserving treatment. 1554 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>