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

Clinical and pathologic findings were compared in 43 postmenopausal endometrial carcinoma patients who had received exogenous estrogens prior to diagnosis and 79 similar patients unexposed to estrogens. Estrogen non-users were more likely to manifest lower parity, later menopause, obesity, hypertension, and diabetes, all of which have been considered to be constitutional risk factors for the development of endometrial carcinoma. Although estrogen users and non-users had similar extent of disease as judged by clinical stage, there was a tendency to more myometrial invasion in hysterectomy specimens from non-users, as well as greater frequency of unfavorable histologic types and grades of tumor. At short-term follow-up, more recurrences occurred in non-users, and this tendency appeared to be independent of clinical stage, histologic type, histologic grade, or modality of treatment. The significance of these and other observation to the determination of the risk-benefit ratio for estrogen administration is discussed.
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PMID:Endometrial carcinoma: clinical-pathologic comparison of cases in postmenopausal women receiving and not receiving exogenous estrogens. 738 46

Various aspects of climacteric treatment with natural human estrogens are discussed. Estradiol, estradiol valerate, estron sulfate, or estriol are used separately or together in various preparations to treat the symptoms of approaching menopause. Estrogen treatment causes proliferation of the endometrium and causes a decrease in LHRH, FSH, and LH secretion. Treatment can take the form of continuous or cyclic treatment with estrogens alone, or sequential estrogne/gestagen preparations can be used. Ovarian function decreases as menopause approaches and results in the cessation of ovulation. Then the hypolutein phase begins, during which the secretion of progesterone is reduced and menstrual bleeding irregularities begin to occur. Eventually, estrogen production decreases so much that menstruation ceases completely, and symptoms such as heat flashes are experienced. Women who want treatment for climacteric symptoms but who want no regular menstrual bleeding can be administered low doses of pure estrogen. Regular abrasio control of endometrial development should be performed, however. Pure estrogen treatment can also be used in the case of hysterectomized women. Otherwise, a sequential treatment is generally indicated. Possible side effects of estrogen substitution therapy are changes in the genitalia, breasts, menstrual bleeding, blood pressure, and weight. There is also an indication that estrogen use can induce endometrial cancer. Besides the definite contraindication of endometrial cancer, relative contraindications of estrogen therapy include breast cancer, reduced liver function, thromboembolic disease, and serious hypertension. Estrogen therapy is to be used to solve acute climacteric symptoms; women should be well informed about possible side effects and that the therapy is no panacea for all menopausal problems.
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PMID:[Peroral treatment with natural human estrogens in the climacteric]. 744 54

Menopause is an endocrinopathy characterized by hypoestrogenism. Estrogen can be replaced easily. Available preparations can be taken by mouth, intramuscularly, transdermally, or transvaginally. Unopposed estrogens increase the risk of endometrial cancer, which can be overcome by the concomitant administration of a progestin agent. The progestin can be administered cyclically either every month, resulting in a monthly menses, or every 3 months, resulting in menses every 3 months. The progestin can also be administered every day, which achieves amenorrhea in over half of the patients; the remainder have breakthrough bleeding. Abnormal bleeding can be assessed by either endometrial biopsy or transvaginal ultrasound.
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PMID:Practical aspects of hormone replacement therapy. 749 85

Estrogen replacement therapy (ERT) has been shown to reduce the risk of cardiovascular disease (CVD) and osteoporosis in postmenopausal women. Studies also indicate a reduced risk of stroke and its consequent mortality among estrogen users, and ERT may also have a role in reducing the risk of Alzheimer's disease and increasing a woman's overall quality of life. On the negative side, some studies show a small duration-related risk of breast cancer with estrogen use and a significant increase in endometrial cancer; the latter is virtually eliminated with the addition of a progestin to the regimen. Although the definitive answer is not yet available, recent epidemiologic data suggest no reduction in protection against CVD and bone fracture with the addition of progestin, which is referred to as hormone replacement therapy, as opposed to using estrogen alone. A woman's potential risks associated with ERT or hormone replacement therapy must be weighed against her lifetime risks of developing CVD, stroke, and bone fracture. The reduction in mortality and morbidity rates with hormone use is generally viewed to be substantial and cost-effective. Health care professionals have an important role in shaping their patients' attitudes. Patients need more information from their physicians about the risks and benefits of estrogen therapy.
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PMID:Benefits and risks of estrogen replacement therapy. 757 95

Endometrial fibroblasts derived from uterine endometrium as controls and endometrial cancer cells (Ishikawa and HHUA cells) were used to analyze the manner of induction of c-Ha-ras transcripts in endometrial cancers, some of which are estrogen-dependent in growth. Estrogen increased c-Ha-ras expression and tyrosine kinase (TK) activity in fibroblast and Ishikawa cells, but not in HHUA cells. Progesterone diminished c-Ha-ras expression and tyrosine kinase (TK) activity induced by estradiol in the fibroblasts, but not in Ishikawa cells, which persistently overexpressed c-Ha-ras. In these cells, epidermal growth factor (EGF) increased c-Ha-ras expression as did estradiol. Pretreatment with tyrphostin, an inhibitor of TK, abolished estrogen-inducible overexpression of c-Ha-ras. The combination of both estradiol and EGF at maximum effective concentration exerted no additive or synergistic effect on induction of c-Ha-ras expression. In conclusion, persistent activation of TK might lead to overexpression of c-Ha-ras in some endometrial cancer cells under estrogen predominant milieu, which might be associated with the transformation or growth potential.
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PMID:Estrogen induces c-Ha-ras expression via activation of tyrosine kinase in uterine endometrial fibroblasts and cancer cells. 757 18

Estrogen receptors of human endometrial cancer Ishikawa cells were found to be present in moderate amounts (160-200 fmol/mg protein), and to specifically bind moxestrol (R2858) with a very high affinity characterized by a Kd around 60 pM, when measured under equilibrium conditions. The binding specificity respected a decreasing order as follows: estradiol (E2: 100%) > 4-hydroxy-tamoxifen (4OHTAM: 52.7%) > estriol (E3: 5.7%) > estrone (E1: 2.1%) > TAM (0.2%). The induction of alkaline phosphatase activity (APase) used as an estrogen-specific response, confirmed the intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT): norethindrone (NOR), norethynodrel and levonorgestrel, at concentrations ranging from 10(-8) to 10(-6) M. The effect of NOR was partially blocked by the antiestrogen 4OHTAM, which was also partially agonistic in this model, but neither by the antiprogestin mifepristone (RU486) nor by the aromatase inhibitor aminoglutethimide. A simulatory effect was also detected at 10(-7) or 10(-6) M with ethindrone, the testosterone- (T) derived progestin homologous to NOR, and with both androgenic parent-compounds, i.e. T and 19NT themselves. In contrast, progesterone (P) derivatives like medroxyprogesterone acetate (MPA) and chlormadinone acetate (CMA) remained totally inactive, as well as 19-nor-progesterone (19NP) itself or its progestagenic derivatives: ORG 2058 and nomegestrol acetate (NOM). Structure-activity relationships deduced from these studies suggest that it is not the absence of the 19-methyl group which can account for the estrogenic potential of the so-called "19-norprogestins", but rather their steroid structure derived from T in a broad sense (including the 19NT derivatives), as opposed to the non-estrogenic therapeutic progestins derived from P like MPA or CMA, or from 19NP like NOM.
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PMID:Lack of estrogenic potential of progesterone- or 19-nor-progesterone-derived progestins as opposed to testosterone or 19-nor-testosterone derivatives on endometrial Ishikawa cells. 757 23

A substantial body of recent experimental, clinical and epidemiological evidence indicates that hormones play a major role in the etiology of several human cancers. The ability of hormones to stimulate cell division in certain target organs such as the breast, endometrium, prostate and the ovary, may lead following repeated cell divisions to accumulation of random genetic errors that ultimately produce the neoplastic phenotype. Hormone-related cancers account for more than 30% of all newly diagnosed female cancers in the United States. While most non-hormone-dependent adult cancers rise continuously with age, hormone-responsive cancers of the breast, the ovary and the endometrium rise with age until menopause, and then distinctly level off to a plateau. These epidemiologic characteristics may indicate that the key etiologic events for these cancers occur in the premenopausal period. Prevention strategies that intervene during the premenopausal period can be expected to have a greater long-term impact in reducing risk than those implemented for an equivalent length of time in the postmenopausal years. Epidemiological studies demonstrate a reduction in endometrial cancer risk of about 11.7% per year of combination oral contraceptive (COC) use; ovarian cancer risk may be reduced by 7.5% per year of COC use, while breast cancer studies have produced mixed results. A comparison of age-adjusted incidence and mortality rates for women less than 50 years of age between the years 1973-1974 and 1986-1987 demonstrate a change in the average rate of breast cancer of plus 9.6% incidence and minus 8.2% mortality; the rates reflect the cancer burden of women who would and would not have had access to COCs during the majority of their child-bearing years. The use of hormone replacement therapy (HRT) is well established to provide short-term relief of symptoms related to menopause and long-term protection from the consequences of estrogen deficiency, such as postmenopausal osteoporosis and cardiovascular disease. Besides COCs, use of HRT constitutes the other major setting in which exogenous steroid hormones are widely used in essentially healthy women and has had a remarkable impact on cancer incidence and mortality. Estrogen replacement therapy (ERT) and endometrial cancer risk are strongly associated with respect to both dose and duration. Endometrial cell mitotic activity during continuous high-dose estrogen monotherapy equals that observed during the follicular phase of the menstrual cycle, and the total mitotic activity over a 28-day period amounts to roughly double that of a premenopausal woman as long as there is no opposition by a progestogen.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Does HRT modify risk of gynecological cancers? 758 88

A women spends about one-third of her life in her postmenopausal years. Some women supplement this period of decreased estrogen production with estrogen replacement therapy (ERT). Many epidemiologic studies have examined the long-term effect of postmenopausal estrogen deprivation and of ERT. Since the 1970s, we have evaluated the risks and benefits of ERT in one population of older women in the California retirement community of Leisure World. ERT is the most effective method for preventing osteoporotic bone loss and fractures in postmenopausal women. In Leisure World, ERT reduced the risk of hip fractures by about 50%. The effect is greatest in longterm users, but may be lost after discontinuation. Postmenopausal osteoporosis affects the bones of the jaws as well as other skeletal bones. Bone loss in the jaws may result in tooth loss. In Leisure World, estrogen users have retained more natural teeth than nonusers. Cardiovascular disease is the leading cause of hospitalization and death in women. In Leisure World, ERT reduced the risk of fatal and nonfatal myocardial infarction, ischemic heart disease, other heart disease, and stroke by 20-40%. The reduction is greatest in long-term and/or current users. ERT is effective in women with and without cardiovascular disease risk factors. One of the most feared aspects of aging is Alzheimer's disease. In Leisure World, women who had used ERT had a reduced risk of Alzheimer's disease. Risk decreased with increasing duration of use. Estrogen use, however, is not without risk. Unopposed estrogen increases risk of endometrial cancer. Risk increases with increasing years of use and remains high after discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The risks and benefits of estrogen replacement therapy: Leisure World. 758 89

Estra-1,3,5 (10)-triene-3,17-diol (17 beta)-, 3-[bis(2-chloroethyl) carbamate] (Estramustine EM) was tested for its anticancer effect on human endometrial cancer cell lines: Ishikawa and its estrogen (E) independent sub-clone EIIL (Estrogen Independent Ishikawa Line). The results showed: (1) EM inhibited growth of both cell lines in a dose dependent manner giving ID50 for Ishikawa as 12 microM and for EIIL as 65 microM. (2) The addition of EM to the culture medium caused cell detachment and death associated with a breakdown of DNA to approximately 90 base pair fragments. (3) Reverse transcription-polymerase chain reaction to examine expressions of c-erbB-2, nidogen and fas showed that EM completely abolished fas expression and resulted in a 40% decrease in nidogen expression in Ishikawa but not in EIIL. No change was seen in c-erbB-2 expression. The present data indicate that the E component of EM does not stimulate the growth of Ishikawa or EIIL. Since the growth of both cell lines was inhibited but apparently in an E receptor (ER) dependent manner, EM may be of value in an adjuvant therapy for endometrial cancer, especially an ER positive one.
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PMID:[Estramustine phosphate, estrogen conjugated with nitrogen mustard inhibits the growth of endometrial cancer cells in vitro]. 777 15

The presenting symptoms, hormonal regimens, treatment modalities, tumor pathology, and follow-up of 25 women developing endometrial cancer while receiving postmenopausal estrogen and progestin therapy were investigated retrospectively. Patients were interviewed and hormone therapies were confirmed through medical records. Pathology specimens were reviewed. Patients received conjugated estrogens (n = 20) or another estrogen (n = 5). For those on conjugated estrogens, the mean daily dose was 0.68 mg, monthly duration was 24.9 days, and monthly dose was 17.0 mg. Women also received medroxyprogesterone acetate (n = 23) or norethindrone acetate (n = 2). The most common regimen was sequential medroxyprogesterone acetate, at a mean daily dose of 7.5 mg, monthly duration of 9.3 days, and monthly dose of 68 mg (mean duration = 5.7 years). Most tumors were low stage and grade, with few demonstrating grade 3 disease (n = 2) or greater than 50% myometrial invasion (n = 2). Twenty-three (92%) had disease limited to the uterus, while two had stage IIIA disease. All are alive and disease-free after a median follow-up of 26 months. Estrogen and progestin therapy does not prevent endometrial cancer in all patients. Women who developed this tumor on sequential therapy in general received less than the recommended guidelines for daily dosage and monthly duration of progestin. Most patients had early-stage and low-grade disease. Continued vigilance in the care of women on hormone replacement therapy is necessary even when combination therapy is prescribed.
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PMID:Development of endometrial cancer in women on estrogen and progestin hormone replacement therapy. 795 53


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