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

Despite reports of studies linking menopausal estrogen therapy with endometrial cancer in 1975, physicians have persisted in considering menopause a condition needing medication--with estrogens. To assess the risks and benefits, NIH held a conference on estrogen usage in postmenopausal women. A panel of physicians heard the therapeutic, epidemiologic, and sociologic evidence and summarized the findings in a final report. It was agreed that estrogen therapy will be effective in combating vasomotor flushes (hot flashes) and vaginal atrophy and dryness. Evidence to justify estrogen use for coronary vascular disease and depression does not exist. Further evidence is needed to deterine whether estrogen therapy will decrease osteoporosis-related fractures. The risk of endometrial cancer increases 4-8-fold following 2-4 years of continuous estrogen usage. It was concluded that estrogens should be prescribed in the lowest effective dosages and for short terms, not exceedng 2-4 years. Cyclic progestin administration and yearly curettage sampling for endometrial cancer might reduce the risk of developing endometrial cancer while on estrogen therapy.
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PMID:Estrogen prescribing practices scrutinized at NIH conference. 52 51

The most important short-term uses of estrogen are in the control of vasomotor disturbances, often called hot flashes, and in the therapy of athrophic vaginitis. Dosage should be as low as possible and on a cyclic basis. Estrogens can be employed cyclically but for an unpredictable term in the case of hypogonadism, female castration, and especially in the treatment of osteoporosis. The synthetic estrogen diethylstilbestrol (DES) is used as a contraceptive after coitus, in a large dose and within 72 hours, since it inhibits implantation of the fertilized ovum in the uterus. The use of estrogens in controlling some of the emotional conditions prior to menopause is not advisable, but they can be helpful in controlling acne and to arrest uterine bleeding. Conversely, estrogens have been shown to be associated with vaginal adenosis, and with clear cell carcinoma in girls whose mothers had been given DES during pregnancy; also with endometrial carcinoma in postmenopausal women who had taken the drug for years. The association between estrogens and breast cancer is still not clear, since the drug produces different results in different patients. Since estrogens increase blood coagulability their use is associated with an increased risk of thromboembolism and cardiovascular accidents. In prescribing estrogens physicians must evaluate each patient carefully, and require regular visits at six month intervals.
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PMID:Estrogens: their function, uses and hazards. Part 2. 62 3

The menopause is centered on the ovary and its in-built obsolescence. The events of the menopause start when the active ovary begins to fail and end when the ovary lapses into inactivity. The duration of these events is variable. Stimulated by the pituitary, 1 follicle develops each month as a hormone-producing organ. The life span of the follicle is then 28 days. Follicles continue to develop unt il none respond to the stimulus of the pituitary. The 32-week fetus has about 7 million primordial follicles. At birth, the number has dropped to 2 million. By puberty only 300,000 3008000 remain. During adult life about 400 follicles will have provided the ova and the hormones. The last few capable of funtion may have poor endocrine function. Ovarian activity is controlled by a "biological clock" in the hypothalamus. This controls the pituitary by a gonadotropin-releasing h ormone. In response the pituitary secretes follicle stimulating hormone (FSH) and luteinizing hormone (LH). The creation of the corpus luteum follows in the ovary and secretes progesterone while estrogen secretion continues. A cyclic drop in pituitary gonadotropin secretions causes the corpus luteum to degenerate. The ovary makes estrogen from cholesterol, converting it to pregnenolone, then to progesterone which is androstenedione to andnostenedione and on to estradiol. Estradiol is the estrogen secreted by the ovary, but it can be changed in the liver t o estrone and estriol. The pathways of the steroid hormone synthesis are the same in the adrenal cortex. When estrogen deficiency occurs in the menopause LH levels increase. Later the FSH is raised and remains high for the rest of life. This raised FSH and low estrogen levels appear to cause the characteristic hot flashes. Abrupt deprivation of estrogen causes more symptoms than a slow decline of function. Estrogen therapy may relieve these symptoms. Prevalence of coronary thrombosis rises sharply in the postmenopausal years. Estrogen-containing pills increase the incidence of venous thrombosis. Estrogen therapy reverses the atrophy of the genital tract. Cycles of treatment imitate the normal action of the functioning ovary but usually are not large enough to promote menstruation. Endometrial cancer appears to be increased by estrogen therapy. It may be that the addition of progesterone would protect against this from of cancer. The adjustment of tissues to an altered hormonal environment and the unrelated changes of aging make complicated problem.
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PMID:The menopause: the events of the menopause. 95 89

A phase I multicenter evaluation of a novel antiestrogen, toremifene, was undertaken in postmenopausal women with various advanced difficult-to-treat malignancies. One hundred and seven women were treated at one of six dosage levels (10, 20, 40, 60, 200, or 400 mg/d orally) for at least 8 weeks. Weekly evaluations for toxicity were conducted. The most common side effects were nausea (31%), vomiting (12%), and hot flashes (29%). Five patients were removed from the study for possible adverse reactions: three patients experienced hypercalcemia; one experienced tremulousness, fatigue, and inability to think clearly; and one had vaginal bleeding. Twelve patients died while on study, 11 with disease progression and one with a pulmonary embolus. Sex hormone-binding globulin (SHBG) levels increased and there was a modest decline in serum antithrombin III levels. Four of 48 assessable patients had partial responses: three with breast cancer and one with endometrial cancer. Toremifene was generally well tolerated at the doses tested.
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PMID:Phase I study of toremifene in patients with advanced cancer. 183 8

Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%). Three patients with bone metastases from breast cancer developed hypercalcemia. At doses greater than or equal to 40 mg/day a decline in LH and FSH occurred which was not statistically significant. At all doses tested SHBG rose during therapy. A dose dependent estrogenic blockade was seen on the vaginal epithelium following challenge with transdermal estradiol. Steady-state concentrations of toremifene were reached within 4 weeks, and at doses greater than or equal to 60 mg/day ranged from 879-3445 ng/ml. The half-life was found to be 5 days, and at three weeks following discontinuation of treatment concentrations greater than 24 ng/ml were detected. The N-desmethyl and 4-hydroxy metabolites achieved steady state levels within 4 weeks and had half-lives of 6 and 5 days respectively. Partial responses were seen in 4 patients, 3 with breast cancer treated at 200 mg/day and 1 with endometrial cancer treated at 400 mg/day.
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PMID:Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. 214 80

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)
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PMID:Estrogen-replacement therapy in patients with previous endometrial carcinoma. 240 7

This review briefly outlines the pharmacology of natural and synthetic estrogens, and synthetic progestins, and summarizes their beneficial and adverse effects for contraceptive and menopausal therapy. Currently, oral contraceptives contain 30-50 mc synthetic estrogen, and 1-5 mg nor-progestin; menopausal therapy may be either 0.625-1.25 mg natural estrogen or estrogen plus 10 mg medroxyprogesterone acetate daily if the woman has her uterus. The biologic effects of estrogens are : decrease in lipoproteins, increased blood coagulation factors, increased blood pressure, decreased glucose tolerance. Progestins increase blood lipids and increase insulin and glucose. Oral contraceptives increase the risk of cardiovascular disease, particularly in smokers and in women over 35, in proportion to dose. These studies should be recapitulated in more detail with the newer low-dose pills. Orals have far more beneficial effects, besides providing an inexpensive, effective method contraception. The death rate of users of oral contraceptives is 3.7/100,000 (1.8 in nonsmokers and 6.5 in smokers), but the risk is 5.5 times higher in nonusers exposed to pregnancy and childbirth. The risk for users of barrier methods backed up by abortion is lower, but pills are cheaper and more acceptable. If woman did not take oral contraceptives, they would not be protected from cancer of the breast, ovary, endometrium, and ovarian and breast cysts. Menopausal therapy puts woman at increased risk of endometrial cancer only if the estrogen is taken alone, not if progestin is combined with the estrogen. There are no other adverse effects except decreased glucose tolerance and possible comprise of lipoproteins if a norprogestin of menopausal estrogens effectively treat hot flashes, depression, vaginal atrophy and bones loss.
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PMID:The adverse effects of hormonal therapy. 351 31

A physician survey was conducted in 13 counties surrounding Albany and Syracuse, N.Y., to determine estrogen prescribing patterns for treatment of problems associated with menopause. A case history of a 51-year-old woman was included in questionnaires sent to the physicians, who were asked how they would treat her in 1981 and how they would have treated her in 1974. Of the 717 questionnaires mailed to gynecologists, internists, and family practitioners, 584 were returned, a response rate of 81 percent. When asked how they would treat the woman, who was described as having frequent, severe hot flashes and other menopausal symptoms, 65 percent of the physicians practicing in both 1974 and 1981 would prescribe estrogen for the patient in 1981; 82 percent would have done so in 1974. Although 87 percent of the gynecologists would have prescribed estrogen both years, the gynecologists surveyed would have decreased daily estrogen doses of 1.25 mg by 72 percent and increased daily doses of .625 mg and .3 mg by 68 percent. Overall, 19 percent of the physicians surveyed would prescribe a daily estrogen dose of 1.25 mg or more for more than 6 months or .625 mg daily for 3 or more years in 1981, compared with 48 percent in 1974. These results suggest that many physicians have responded to the increasing evidence in the literature of a link between using estrogen to treat menopausal symptoms and endometrial cancer by switching from high doses of estrogen for long durations to smaller doses for shorter durations. Many physicians are also simply prescribing estrogens for fewer patients.
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PMID:Prescribing estrogen during menopause: physician survey of practices in 1974 and 1981. 643 92

The three primary indications for estrogen replacement therapy in postmenopausal women are severe vasomotor symptoms (hot flashes), prevention or treatment of osteoporosis, and atrophy of the genital tract. Estrogen replacement therapy is well established as reducing the morbidity and mortality associated with osteoporosis. The increased incidence of endometrial cancer associated with estrogen use (from 1/1,000 to 4/1,000 per year) must be accepted and viewed in perspective. Many of these estrogen-related cancers are stage I lesions, with a cure rate of 95%. In addition, the risk associated with estrogen replacement therapy can be reduced by coadministration of a progestogen during the last ten days of the cycle.
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PMID:Estrogen replacement therapy--boon or bane? Current status of the controversy. 670 Nov 32

Controversy regarding almost all aspects of hormone replacement therapy continues. Interest in active management of the menopause and its problems is increasing at a time when it is becoming more and more difficult to evaluate the literature -- over 100 articles each year on the subject. Currently, few authorities disagree with the concept of short-term estrogen therapy for hot flashes or vaginal atrophy, yet when long-term hormonal replacement therapy is advocated the controversy begins. Some women appear to need long-term therapy for persistent vasomotor symptoms and genital atrophy, and a strong economic argument has been made for long-term estrogen replacement in all postmenopausal women to reduce the later incidence of symptomatic osteoporosis. Estrogens in a dosage equivalent to 0.625 to 1.25 mg of estrone sulphate can greatly reduce the rate of postmenopausal cortical bone loss, demonstrable osteoporosis and the incidence of fractures in later years. Most leading authorities are against unrestricted estrogen use. The primary concern is that of endometrial cancer developing in a few susceptible women who receive long-term estrogen therapy. Recent evidence supports that a dose and duration related risk exists, but that the risk is probably low, that the cancer is generally diagnosed early, is of relatively low malignancy, and responds with an excellent prognosis to adequate surgical treatment. There is no question that patients receiving long-term estrogen therapy need continuing medical supervision.
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PMID:Long-term oestrogen usage and the postmenopausal woman. 678 Jul 71


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