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)

To prevent hyperplasia and carcinoma of the endometrium during oestrogen replacement therapy (ORT), the addition of progestogens once a month is considered mandatory. However, there is no sound scientific basis for this assumption. As the addition of progestogens has several disadvantages, it is important to minimize the frequency of progestogen addition. Vaginosonography is a rather new technique which has not yet been used for monitoring ORT. In this study the increase in endometrial thickness, as measured by vaginosonography, was taken as an indicator of stimulation of the endometrium by oestrogens. Oestrogen treatment was started in post-menopausal women with little endometrium (thickness less than 3 mm). As long as there was virtually no increase during oestrogen treatment, no progestogen was added, but where considerable growth occurred (greater than 3 mm) progestogen was administered. By means of vaginosonography the growth of the endometrium can be monitored precisely on an individual basis. It is thus possible to distinguish women with a slow growing endometrium from those with an endometrium that grows fast. In this way it will perhaps become possible to minimize progestogen addition during ERT by tailoring dosage to individual requirements.
 ...
PMID:Monitoring of oestrogen replacement therapy by vaginosonography of the endometrium. 152 30

For patients with previous endometrial cancer, ERT is not the accepted practice in the U.S. The therapeutic dictum that estrogen is contraindicated in patients with previous uterine adenocarcinoma is, however, not substantiated by clinical data. The relation of unopposed estrogen stimulation to endometrial hyperplasia and carcinoma, and the published studies relating ERT to endometrial cancer, have resulted in the clinical perception--and cautionary statements to that effect--that estrogen is contraindicated for patients with a history of endometrial carcinoma. The exact biologic effects of ERT on endometrial adenocarcinoma have not yet been studied adequately, however; the initial clinical data suggest that there is no increase in recurrence or mortality. In the meantime, the clinician is left with contradictory data as a basis for determining the proper management of symptomatic patients. The total impact of estrogen deficiency on the health of women and the ratio of benefits and risks of ERT are yet to be defined completely. The preponderance of evidence suggests that estrogen has a beneficial effect on the major cause of death in women, coronary heart disease, by increasing the high-density lipoprotein (HDL) fraction of cholesterol. It is established that estrogen prevents the demineralization of bone and delays the ravages of osteoporosis. No one has died from vaginal atrophy, bladder dysfunction, or hot flashes; the quality of life and marriage have been improved, however, by relieving these symptomatic conditions with ERT. Several studies have attempted to analyze with various statistical models the ratio of benefits to risks, and the majority of authors have concluded that the beneficial effect on cardiovascular disease alone clearly outweighs any known risk.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Estrogen-replacement therapy in patients with previous endometrial carcinoma. 240 7

Early age at natural menopause or bilateral ovariectomy substantially reduce a woman's lifetime risk of breast cancer. Reversible 'bilateral ovariectomy' can now in effect be achieved by 'high-dose' luteinising hormone releasing hormone (LHRH) agonists (LHRHAs). The harmful effects of such medical reversible bilateral ovariectomy, in particular the increased risks of coronary heart disease and osteoporosis, can in all likelihood be obviated by 'low-dose' oestrogen replacement therapy (ERT), specifically 0.625 mg of conjugated equine oestrogens (CEE) for 21 days in each 28-day treatment cycle, and such ERT use will only negate to a relatively small extent the beneficial effect of such bilateral ovariectomy on breast cancer risk. We calculate that such an LHRHA plus low-dose ERT regimen given to a premenopausal woman for 10 years will, in addition to being a most effective contraceptive, decrease her lifetime risk of breast cancer by more than 50%. We calculate that such a 10-year regimen will also decrease her risk of ovarian cancer by two-thirds. This regimen should leave endometrial cancer risk and bone metabolism unaltered, and may reduce the risk of heart disease. The addition of a 'low-dose' progestogen to the regimen for 12 days in each 28-day treatment cycle would be beneficial to the endometrium, but it will adversely affect risk factors for heart disease and it may significantly reduce the benefit of the regimen as regards breast cancer. A satisfactory compromise may be to add a low-dose progestogen for 12 days at less frequent intervals. Another possibility may be to deliver a progestogen solely to the endometrium with an intra-uterine device; the benefits of such a regimen would be a significant reduction in the incidence of breast, ovarian and endometrial cancer.
 ...
PMID:LHRH agonists and the prevention of breast and ovarian cancer. 267 44

Tamoxifen is actually considered the drug of choice for the hormonal treatment of early and metastatic breast cancer due to its efficacy and low toxicity. In addition, clinical trials of adjuvant therapy have demonstrated a 35% decrease in controlateral breast cancer in women receiving tamoxifen compared with controls, suggesting a potential role for this drug in chemoprevention of breast cancer in healthy women at increased risk of disease. Although tamoxifen is usually classified as an estrogen antagonist it also has partial estrogenic effects in some tissues such as liver, bone and uterus. The estrogenic action of tamoxifen on lipid metabolism and bone mineral density suggests additional benefits in protection against cardiovascular diseases and osteoporosis in postmenopausal women. Of particular interest could be the use of tamoxifen as an alternative to traditional estrogen replacement therapy in postmenopausal women previously treated for breast cancer or at increased risk of disease due to family history or histology on breast biopsy. The potential adverse effects of tamoxifen are partially similar to those of ERT and includes an increased risk of endometrial cancer, hepatic diseases, thromboembolic alterations and ocular toxicity. The mechanism of action of tamoxifen is briefly examined and the potential toxic effects and benefits of tamoxifen treatment are discussed.
 ...
PMID:Metabolic effects of tamoxifen in postmenopause. 784 May 29

The most important benefit of ERT may well be its cardioprotective effect. But unopposed estrogen therapy also carries the risk of inducing endometrial cancer. A compelling body of evidence indicates that adjunctive progestogen protects effectively against estrogen-induced endometrial adenocarcinoma, and that progestogen therapy is effective in the treatment of hyperplasia in most women who have taken unopposed estrogen. Yet there is concern that adjunctive progestogen may attenuate the cardioprotective effects of estrogen. It is therefore agreed that adjunctive progestogen therapy is not indicated for hysterectomized women, and should be given at the lowest effective dose to non-hysterectomized women. Phase II dose-ranging clinical trials using secretory transformation as an efficacy endpoint to estimate protective effects of different doses of progestogen against endometrial hyperplasia/adenocarcinoma are complicated by the possibility that the doses protecting against hyperplasia may differ from those producing secretory changes. Further work is needed to identify one or several progestogen-regulated markers that most closely correlate with protection against estrogen-induced endometrial cancer.
 ...
PMID:Aspects of hormone replacement therapy. 797 28

Since postmenopause unopposed oestrogen replacement therapy (ERT) increases the incidence of endometrial carcinoma, the addition of a progestin in non-hysterectomised women is mandatory for hormonal substitution. On the other hand, progestins have a negative influence on serum lipids and may thus put in question the benefits of the ERT with regard to the cardiovascular risk. Progestins lower HDL and increase LDL in a dose-dependent way according to their chemical structure. In the present non-randomised study, the influence of a cyclic combined oestrogen progestin substitution on the serum lipids has been measured. From a total of 90 apparently healthy postmenopausal patients, 59 received a transdermal ERT with 17 beta-Estradiol (Estraderm TTS 50), whereas 31 women obtained a daily dose of 0.625 mg conjugated equine oestrogens (CE) perorally. Additionally all patients were given 10 mg medroxyprogesterone-acetate (MPA) daily during the first 10 days of each month. After 6 months of therapy, the following changes of serum lipids, expressed as percentage of initial values, were measured: total cholesterol in the transdermal group -2.3% (n.s.), in the peroral group -11.8% (p < 0.00001); triglycerides -3.7% (n.s.) resp. +8.6% (n.s.); HDL cholesterol + 0.2% (n.s.) resp. -1.8% (n.s.); LDL cholesterol +1.3% (n.s.) resp. -14.8% (p < 0.00001). The calculated atherogenic indices showed a decrease in the peroral substituted group of -6.5% (n.s.) for the HDL/total cholesterol ratio and -14.8% (p < 0.002) for the LDL/HDL ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Cyclical gestagen (MPA) supplement for continuous transdermal or oral estrogen substitution in postmenopause: modification of serum lipids]. 827 Jan 55

In the treatment of locally advanced carcinoma of the uterine cervix the multimodal therapeutic approach is useful to improve overall survival and disease-free survival. Two studies of concomitant radiochemotherapy were conducted. In the first, recurrences of gynecologic tumors were treated, in the second primary tumors of the uterine cervix. In the first study 29 patients, of whom 15 with endometrial cancer recurrence, 10 with cervical cancer recurrence and 4 with vulvar cancer recurrence were treated with FUMIR schedule (5-FU and mitomycin C plus concomitant radiotherapy to the pelvis in two cycles of 23.4 Gy) and subsequent brachytherapy boost. In the second study 17 patients, of whom 14 evaluable, were treated with external beam radiotherapy (ERT 40 Gy) and concomitant chemotherapy (5-FU and CDDP). Before and after treatment the patients were examined with MRI. After radiochemotherapy radical hysterectomy and histology of surgical specimen was performed. Results of first study were as follows: acute G1-G2 (RTOG) hematologic toxicity 56%, G3 4%; G1-G2 gastrointestinal 54%, G1-G2 skin 29%; G1-G2 rectum 24%; G1-G2 bladder 25%; G1-G2 vagina 30%. Local control, overall survival and disease-free survival at 24 months were 45%, 76% and 67%, respectively. Results of the second study showed 9/14 patients with complete response and 4/4 patients with partial response (93%), no change in 1, with 100% MRI accuracy as compared to histology. Based on these results a phase III clinical trial was planned in primary cancer of the uterine cervix using concomitant radiochemotherapy (CDDP + 5-FU) plus intracavitary brachytherapy for organ preservation.
 ...
PMID:Organ preservation in locally advanced carcinoma of the uterine cervix. 944 53

The benefits of oestrogen replacement therapy (ERT) in preventing vasomotor symptoms, cardiovascular disease, osteoporosis, and colon cancer are well documented. Other potential benefits i.e. dementia and macular degeneration are being investigated. Although oestrogen is said to be contraindicated in women previously treated for breast and endometrial cancer, there is no data to support this admonition. Preliminary data would suggest ERT can be used safely in women who have had these cancers. Prospective randomised studies are currently on going in the United States and Europe addressing ERT in previously treated breast and endometrial cancer. Informed consent, patients' desires, and benefit-risk considerations are all part of information the woman needs to make a decision concerning ERT.
 ...
PMID:HRT and women who have had breast or endometrial cancer. 1069 60

Fifteen percent of premenopausal women, 10-40% of postmenopausal women, and 10-25% of women receiving systemic hormone therapy experience urogenital atrophy. The most common symptoms are dryness, burning, pruritus, irritation, and dyspareunia. Estrogen loss, drugs, and chemical sensitivities are causes. Estrogen or hormone replacement therapy (ERT-HRT) is the treatment of choice in postmenopausal women. Dosages prescribed for menopause symptoms or to prevent osteoporosis (and, potentially, other conditions) can restore the vagina to premenopausal physiology and relieve symptoms. Concomitant progestins are necessary for women with an intact uterus to minimize or eliminate estrogen-induced endometrial cancer. Low-dosage oral and vaginal ERT can relieve urogenital atrophy but might not produce systemic effects. Progestins are not necessary with vaginal rings and vaginal tablets. If ERT is given only to treat urogenital atrophy, estrogen creams 1 or 2 times/week may prevent recurrence after symptoms are resolved. Progestins are not required for occasional estrogen cream use. Vaginal moisturizers provide longer relief by changing the fluid content of endothelium and lowering vaginal pH. Vaginal lubricants provide short-term relief. Women with contraindications to ERT-HRT could use lubricants for intercourse-related dryness or moisturizers for more continuous relief. The lay press promotes agrimony, black cohosh, chaste tree, dong quai, witch hazel, and phytoestrogens for vaginal dryness and dyspareunia; however, no evidence exists to support these specific claims. Pharmacists should be actively involved in identifying, preventing, and treating urogenital atrophy.
 ...
PMID:Urogenital atrophy: prevention and treatment. 1131 May 20

Sex steroids are not known to damage DNA directly. They can stimulate or inhibit cell proliferation, and thus can modulate tumor developmental progression. Sex steroid-related tumors in women are represented by breast cancer and endometrial cancer, and a possible relationship exists between sex steroids and both ovarian and colon cancer. Among current ERT users or those who stopped use 1-4 years previously, the relative risk of having breast cancer diagnosed increases by a factor of 1.023 for each year of hormone use. This increase is comparable with the effect on breast cancer of delaying menopause, and seems to be largely limited to lean women. The breast cancers diagnosed during ERT are more likely to contain ER and are less aggressive. Some reports indicate no increase in breast cancer mortality in HRT users. Recent data suggest that an estrogen-progestin regimen may increase breast cancer risk beyond that associated with estrogen alone. However, the effect of progestogens on the breast awaits further clarification. ERT/HRT is generally considered to be contraindicated in breast cancer patients, as no firm data are yet available from randomized clinical trials. Despite the potential risks, ERT/HRT could be considered for breast cancer patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given, particularly in women with ER--(hormone-resistant) cancers. Unopposed estrogen therapy is known to increase endometrial cancer risk, and is appropriate only for hysterectomized women. To negate the excess risk of endometrial hyperstimulation, an adequate progestin dose must be given in a continuous combined regimen or for an appropriate number of days in sequential regimens (10 days or more for some progestogens or 12 days or more for other progestogens). An appropriate combination of estrogen and progestin does not appear to increase, and may even decrease, the risk of endometrial cancer. HRT is generally considered to be contraindicated in endometrial cancer patients. Despite the potential risks, HRT could be considered for patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given. Available data suggest a reduced risk of colorectal adenoma and colon cancer in current users of HRT, but definitive studies are still needed. There is no contraindication to HRT prescription in colon cancer survivors. Consistent epidemiological data describe a decreased incidence of ovarian cancer with oral contraceptive use during the reproductive years. Studies on HRT and risk of epithelial ovarian cancer have produced conflicting results but most data seem to exclude a strong association. While no data contraindicate HRT use in epithelial ovarian cancer survivors, current studies do not allow us to exclude the possibility that estrogens alone could stimulate ovarian cancer growth in a small fraction of patients. Additional studies are required. It is important to consider that not all estrogens and progestins are used with the same dosage, route of administration (oral, transdermal and for estradiol intranasal) and, mostly, different estrogens do not show the same bioavailability and tissue effects. The available data do not allow to discriminate for all these variables and therefore it is inappropriate to consider jointly all forms of hormonal therapy. This issue is considered as an important area for future evaluation and research. The International Menopause Society is in the process of drawing up specific recommendations for further research in the field of HRT and cancer.
 ...
PMID:Controversial issues in climacteric medicine II. Hormone replacement therapy and cancer. International Menopause Society Expert Workshop. 9-12 June 2001, Opera del Duomo, Pisa, Italy. 1158 39


1 2 Next >>