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

Estrogen use for treating symptoms of menopause and in oral contraception is under growing attack Recent findings have shown negative correlations between oral contraceptive (OC) use and myocardial infarction, elevated risk of breast cancer, endometrial cancers among wo men between 21 and 39 years of age (especially among those using sequent ial pills) and benign tumors of the liver. Studies have also linked prolonged estrogen therapy in menopausal women with increasing incidence of endometrial cancer. An estimated 5.6-fold increase in endometrial cancer risk has been figured for women who have been using estrogen from 1 to 4.9 years. Consequently, the FDA has announced plans to label all estrogen products with strong restrictive warnings. There is a possibility that sequentials will be removed completely from the market The increasing number of reports of various effects of estrogen still await resolution.
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PMID:More critics raise voices against estrogen therapy. 1222 1

Ever since a gradual but significant reduction in the estrogenic and progestogenic components of oral contraceptives (OCs) was made, there has been a corresponding decrease in adverse effects associated with the pill. The beneficial effects include prevention of pregnancy, reduction in pelvic inflammatory disease, protection against ovarian/endometrial cancer and benign breast tumors and ovarian cysts, reduction in the occurrence of rheumatoid arthritis among OC users, and regulation of the menstrual cycle. The adverse effects include diseases of the circulatory system (myocardial infarction, venous thromboembolism, subarachnoid hemorrhage, hypertension), possible carcinogenicity (breast, cervix, melanoma), pituitary adenomas, liver disorders, glucose metabolix effects (diabetes), vitamin status alteration, delay in return of menstruation and fertility, and a number of minor side effects (nausea, vomiting). Contraindications to OC use include history of malignancy of the breast or genital tract, venous thromboembolism, cerebrovascular accident, undiagnosed abnormal vaginal bleeding, focal migraine, or familial hyperlipidemia. The following situations require medical assessment before OCs are prescribed, and medical supervision if OCs are prescribed: age 40+, smoking and age over 35, mild hypertension or a history of hypertensive disease of pregnancy (toxemia), epilepsy, diabetes mellitus, history of bouts of depression, history of oligomenorrhea or amenorrhea in nulliparous women, and gallbladder disease. Problems could occur with OC use in the following situations: 1) lactation (ideally, OCs should be withheld until the child is weaned but if not possible, OCs should not be given until lactation is established); 2) drug interaction (other contraceptive form should be used when the patient is taking antibiotics or anticonvulsants); 3) tropical diseases (studies are still underway); 4) adolescence (very young girls should use other contraceptive method until regular menstruation is established); 5) postcoital contraception (limited use of steroids in emergency situation); and 6) hormonal pregnancy tests (use of oral steroids for pregnancy testing is not recommended). The 3 main types of OCs currently used are the combined estrogen and progestagen, the progestagen-only OC, and the triphasic OC. The lowest effective dose of a compound should be used, and healthy women may continue to use OCs for many years.
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PMID:Statement on steroidal oral contraceptives. 1226 73

Reports regarding the question of whether oral contraceptive (OC) use enhances the risk of cancer or one of several serious cardiovascular disorders, i.e., thromboembolic disease, stroke, and myocardial infarction are reviewed. In 1974 the Royal College of General Practitioners (RCGP) issued an interim report of a large prospective study involving 46,000 women. The study found a 5-fold increase in the risk of deep venous thrombosis among women taking OCs. Laboratory studies have tried to establish a direct causal relationship between OC use and altered hemostatis. In review of these studies, Bingel and Benoit reported an increased incidence of thromboembolism in OC users with blood group A. Other hemostatic alterations in OC users were also noted. Other investigators have examined the effect of OCs on antithrombin 3. In 1 study, the inhibitory activity of antithrombin 3 on factor X was significantly reduced among 57 women using the combined OCs, but there was no substantial difference in the quantity of antithrombin 3 in these women as compared with 48 women in the control group. In 1 retrospective case control study of 60 surgical patients with complications of pulmonary embolism or venous thrombosis, the risk of postoperative thromboembolism was 6.7 times greater in OC users than in 97 well matched surgical controls. The RCGP study showed that the risk of cerebrovascular disease in women using OCs was 4 times greater than in nonusers. This finding was substantiated by the Boston-based Collaborative Group for the Study of Stroke in Young Women, which observed a 2-fold increase in risk for all types of stroke among OC users. Several studies have demonstrated that serum lipids are higher in women who use OCs than in those who do not, with estrogen being implicated as the cause of the elevation. Other studies have attempted to link serum lipid elevations to myocardial infarction, but the association is unclear. Both epidemiological and laboratory studies have implicated OCs in the genesis of essential hypertension. Several studies have examined mortality trends associated with OC use. In 1 analysis of data from 21 countries, women between 15 and 44 years of age were found to have a 3-fold to 5-fold increase in cardiovascular mortality that was associated with OC use. The principle evidence that suggested a possible link between OCs and breast carcinoma derived from experiments in laboratory animals. There is no conclusive evidence that OCs cause breast cancer in humans. The association between OC use and endometrial cancer is also inconclusive at this time. A marked increase in the incidence of hepatic adenomas among OC users has also been noted recently. The following other effects associated with OC use are reviewed briefly: glucose tolerance tests; birth defects; gallbladder disease; postpill amenorrhea; laboratory tests; and drug activity. Absolute and relative contraindications for OC use are listed.
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PMID:Oral contraceptive risks: a realistic appraisal. 1227 76

Outlined is a protocol for the administration of emergency contraceptive pills. The indication for such treatment is unprotected intercourse within the past 72 hours. Absolute contraindications include the possibility of an existing pregnancy and a family history of stroke, heart attack, thrombophlebitis, breast or endometrial cancer, or liver tumor. Possibly excluded, depending on evaluation by a physician, are women with abnormal vaginal bleeding, active hepatitis, active gallbladder disease, high blood pressure, acute focal migraine, breastfeeding women, and those unable to understand instructions. The recommended regimen consists of six tablets of Ovral (two taken immediately, two more in 12 hours) or 12 tablets of Lo/Ovral, Nordette, or Levlen (four taken immediately, repeat dosage in 12 hours). The extra pills are to be used in cases of vomiting within three hours of pill ingestion. Women with a history of oral contraceptive-related nausea and vomiting should be provided with Compazine. Women should be informed that this method is effective in only about 92% of cases. All women who receive emergency contraception should be counseled that this is strictly a back-up method and helped to formulate a long-term birth control strategy.
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PMID:Emergency contraceptive pills (ECP) protocol. 1228 80

New types of contraception approved for use in the US include two long-lasting, hormone-based contraceptives, Depo-Provera and Norplant, and the female condom. The female condom is made of polyurethane, which is thinner, stronger, and a better conductor of heat than latex. Its inner ring fits over the cervix and the outer ring protects the labia and the base of the penis. Its typical-use and perfect-use failure rates are 21-26% and around 5%, respectively. One injection of Depo-Provera blocks ovulation for 3 months. Irregular periods are common with Depo-Provera use. Fertility may not return for 6-12 months after discontinuation. Depo-Provera may protect against endometrial cancer. The 6-capsule system Norplant is inserted subdermally in the arm and releases levonorgestrel for up to 5 years. Since its arrival on the US market, more than 900,000 women have used Norplant. Contraindications to Norplant are liver disease, blood clots, inflammation of the veins, history of breast cancer, or breast feeding in the first 6 weeks postpartum. More than 600,000 US women undergo sterilization annually. 25% of all heterosexually active, fertile women of reproductive age and 60% of these women ages 35-44 have had a tubal ligation. Vasectomy is less risky than tubal ligation. Both vasectomy and tubal sterilization are more than 99% effective. Oral contraceptives (OCs) suppress ovulation. 28% of US women of reproductive age use OCs. OCs are more than 99% effective. OCs appear to increase the risk of blood clots, heart attack, and stroke for smokers over 35. Health benefits of OCs include protection against ovarian cancer, endometrial cancer, pelvic inflammatory disease, ovarian cysts, and benign breast tumors. Barrier methods keep sperm from joining the egg. Latex condoms protect against sexually transmitted diseases (STDs). IUDs interfere with sperm transport and egg fertilization. In the US, there is a perception that IUD use is unsafe. Women with new or multiple partners should use condoms to protect against STDs.
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PMID:Choosing a contraceptive. What's best for you? 1229 May 58

The use of oral contraceptives (OC) by an estimated 150 million women worldwide has prompted concern about their potential risks. But, there are also health conditions--medical and surgical disorders, reproductive tract cancers, and menstruation disorders--that oral contraceptives affect beneficially. OC users have a lower risk of iron deficiency anemia, an important consideration for nutritionally deficient women. The risk of developing pelvic inflammatory disease is also decreased in OC users, as is the risk of ectopic pregnancy. This is important for women in developing countries, where access to medical services for a life-threatening ectopic pregnancy might be limited. Using OCs lowers the incidence of surgery for benign breast disease, the incidence of retention cysts of the ovary, the risk of endometrial cancer, the risk of epithelial ovarian cancer, and relieves symptoms of dysmenorrhea and premenstrual syndrome. The risks associated with OC use, including stroke and heart attack, vary among age groups, smoking status, and other cardiovascular risk factors. For example, elevated serum cholesterol is lower among women in developing countries, so the associated risk of heart attack is lower for these women. Other complications associated with OC use are deep-vein thrombosis, pulmonary embolism, gallbladder disease, and hepatic adenoma. There is controversy about whether OC use increases the risk of cervical neoplasia. Studies that have attempted to define this risk are subject to methodological problems, in that increased surveillance of OC users results in a higher rate of detection. Some controversy exists about OC use and an increased risk of breast cancer, but no definitive results are available. Although the risks associated with OC use can be serious, these risks are only slightly higher among OC users compared with non-users. The benefits, such as reduced risk of serious diseases and gynecological disorders, seem to outweigh the risks, pointing to the need for accurate communication between health professionals and the women they advise about contraceptive choices.
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PMID:Beyond contraception: the health benefits and risks of the pill. 1231 33

This report summarizes a meeting of the IPPF International Medical Advisory Panel (IMAP) held in November, 1986, at which information on steroidal oral contraception (OC), Acquired Immunodeficiency Syndrome (AIDS), and female sterility were discussed. Regarding the multiphasic OC now in use, the benefits to health and well-being outweigh the possible side-effects and infrequent complications. Use is associated with a lower incidence of pelvic inflammatory disease, 96-98% effective prevention of pregnancy, a protective effect against ovarian and endometrial cancer, and regulation of erratic menstrual cycles. Minor side effects include nausea, vomiting, dizziness, headache, fluid retention, and inter-menstrual spotting. Adverse effects are circulatory system disease, myocardial infarction, venous thromboembolism, elevated blood pressure, and liver disease. Data on possible carcinogenicity have been conflicting. For women over age 40 OCs should be prescribed with caution. IMAP also drew up recommendations to assist FPAs to play a more active role in controlling the spread of AIDS. An effective program of Information and Education is of primary importance, targeting family planning workers and clients, teachers, parents, and employers. Wide promotion of condom use is a priority. Studies in Africa have revealed a major epidemic of AIDS, with the major mode of transmission heterosexual. The only immediate practical step in prevention of spread is by changes in sexual behavior. The last topic discussed is that of sterility in African women. The naturally occurring level of infertility expected in all populations of women is 3%; high levels in Africa vary by region from 3-32%. These levels of sterility are acquired through infection with Neisseria gonorrheae and Chlamydia trachomatis. Silent infection of women with Chlamydia make treatment especially difficult.
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PMID:Statement on steroidal oral contraception. 1234 Sep 76

Smoking is dangerous for all women, regardless of the method of contraception used. Women who smoke and take the oral contraceptive pill should stop smoking, since the combined effect of smoking and oral contraception may increase a woman's risk of heart attack compared to smoking only. Since women under age 35 who smoke and use the pill are at greater risk of death from pregnancy and childbirth than from using the pill, smoking and not oral pill use should be eliminated from their lives in the interest of practicing a safe and highly effective mode of birth control. Pill use is definitely not recommended for women aged 35 and older who smoke. Many programs exist to help one stop smoking. Stopping smoking is very important to reduce one's risk of stroke whether or not the pill is being used. Exactly how much the pill may or may not increase a woman's risk of getting a blood clot is controversial, although blood clots among otherwise healthy pill users who do not smoke are rare. In addition to being a very safe method of birth control which is highly effective when taken correctly and consistently, birth control pill use protects women against ovarian cancer, endometrial cancer, painful or irregular periods, breast cysts, iron deficiency anemia, ectopic or tubal pregnancy, and infections of the fallopian tube requiring hospitalization. Healthy, nonsmoking women can safely take the pill right up until menopause.
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PMID:The truth about oral contraceptives, heart attack, stroke and blood clots. 1234 1

When choosing a method of contraception, a woman must consider the pros and cons of various methods together with her family physician. In this process, the doctor provides information on the advantages and disadvantages, while the woman decides. A sub-50 pill of the second-generation preparation is the oral contraceptive of choice. If the woman chooses a newly developed method of contraception, she must be carefully informed about the uncertainties with regard to reliability and safety. Oral contraceptives are absolutely contra-indicated in the following cases: a history of myocardial infarction, stroke (CVA), venous thromboembolism, a known coagulation-factor deficiency, breast or endometrial carcinoma or severe liver-function disorders. Non-hormonal methods of contraception are preferred in such a case. If there are two or more risk factors for cardiovascular disease, the doctor and the patient must consider the pros and cons of hormonal contraception. In this connection, stopping smoking is more effective than not using an oral contraceptive. A prescription for an oral contraceptive can be given without a physical examination, not even a measurement of the blood pressure; follow-up is only necessary in the case of side effects or questions. Progestagen-only contraceptives are absolutely contraindicated in the following cases: current venous thromboembolism, vaginal bleeding of unknown origin, progestagen-dependent tumours such as breast cancer, and severe liver function disorders.
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PMID:[Summary of the practice guideline 'Hormonal contraception' (second revision) from the Dutch College of General Practitioners]. 1552 40

Atypical endometrial hyperplasia has been associated with progression to endometrial cancer, the most common genital malignancy. There are multiple risk factors for endometrial cancer, such as early menarche, exogenous estrogen exposure, obesity and diabetes. Diabetics have a 3-4 fold relative risk of endometrial cancer. Also, several studies have demonstrated an association between insulin resistance and endometrial cancer. There is known the first description of atypical endometrial hyperplasia resistant to progestogen therapy, which was subsequently treated with an insulin-sensitizng agent, metformin. Metformin is a biguanide antihyperglycemic agent used in the treatment of adult-onset diabetes. Unlike the sulfonylureas, metformin does not act primarily by increasing insulin secretion. In contrast, metformin lowers the rate of gluconeogenesis in the presence of insulin. Therefore, it is considered an insulin-sensitizer. Increased insulin sensitivity may improve the metabolic effect of insulin and decrease its mitogenic effect by tissue-specific mechanisms. One explanation for tissue specific differences in insulin binding and action may be through the relative expression of the insulin receptor (IR) isoforms. The IR isoforms IR-A and IR-D differ by 12 amino acid residues, owing to the alternative splicing of exon. The IR-A is predominantly expressed in malignant tissues and may lead to mitogenic effects within the cell. The relative expressions of IR-A and IR-B in normal and malignant endometrial tissue is not known. Besides direct effects on the IR, several additional mechanisms have been proposed for the mitogenic effect of insulin in endometrial cancer. In addition to the possible direct mitogenic effects of insulin through the IR-A, insulin resistance may be associated with alterations in expression of insulin-like growth factors (IGFs) and the IGF binding proteins (IGFBPs) or may inhibit the protective effect of progestagens. Binding sites for IGF-1 and IGF-2 have been confirmed in both normal and malignant endometrium. Binding of IGF-1 is significantly higher in endometrial cancer compared to normal endometrium. In the Ishikawa human endometrial cancer cell line IGF-1 was a more potent mitogen than insulin or IGF-2. Insulin may increase mitogenicity by regulating the expression of IGFBPs. The IGFBPs are a family of proteins that have both proliferative and anti-proliferative effects. While all six high-affinity IGFBPs are expressed in the endometrium, IGFBP-1 is the best characterized. Hyperinsulinemia can decrease IGFBP-1 even in the presence of progesterone, perhaps inhibiting progesterone's protective effects. Interestingly, IGFBP-1 was undetectable or minimally expressed in endometrial cancers. Nestler discussed results of a 6-month treatment of 100 nonebese women with PCOS, which showed a somewhat greater effect of metformin than rosiglitazone and no benefit of administering both agents in combination. Long-term treatment with oral contraceptives decreases endometrial cancer, with a reduction in serum androgens and a decreases in hirsutism and acne, but may worsen insulin resistance and lead to deteriration in glucose tolerance. Insulin sensitizers, on the other hand, should decrease endometrial hyperplasia by inducing regular menses, but may not be as beneficial in improving androgen - related symptoms. Note that the Nurses Health Study (NHS) showed increased risk of diabetes in oral contraceptive users. These considerations may be related to the finding that women who used oral contraceptives have increased risk of myocardial infarction. Thus, in view of the particular increase in CVD risk among women with PCOS, one might be less likely to recommend oral contraceptives, while insulin sensitizers may be of particular benefit, decreasing androgens, improving ovulation and fertility, and reducing the risk of diabetes and CVD. Theoretically, metformin, a treatment which is now widely used to treat infertile women with PCOS, may have a role in preventing endometrial hyperstimulation by lowering insulin concentrations and restoring ovulation. However, the long-term effects of this drug in women with PCOS are not known and more studies are required before suggesting its use for preventing endometrial cancer.
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PMID:[Molecular action of insulin-sensitizing agents]. 1635 Jul 24


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