phytoestrogens and Endometrial-Neoplasms

Phytoestrogens are widely used by postmenopausal women for the treatment of the climacteric syndrome. The risk of adverse effects of this treatment, however, is unknown.. Using a fixed-effects model, we performed a meta-analysis of side effects comparing phytoestrogen treatment with placebo or no treatment in randomized controlled trials.. We identified 174 randomized controlled trials. Side effects were reported in 92/174 randomized controlled trials with 9629 participants. The overall incidence of side effects in the phytoestrogen and control groups was 2019/5502 (36.7%) and 1824/4806 (38.0%), respectively (P=.2; incidence rate ratio [IRR] 1.01; 95% confidence interval [CI], 0.95-1.08). Comparing various side effect categories, we found significantly higher rates of gastrointestinal side effects among phytoestrogen users (P=.003; IRR 1.28; 95% CI, 1.08-1.50). Gynecological (IRR 0.94; 95% CI, 0.74-1.20), musculoskeletal (IRR 1.20; 95% CI, 0.94-1.53), neurological (IRR 0.91; 95% CI, 0.70-1.19), and unspecific side effects (IRR 0.95; 95% CI, 0.88-1.03) were not significantly different between groups. Within side effect categories, we found no significantly higher rates of side effects in women using phytoestrogens. Specifically, the rates of hormone-related side effects such as endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly different between groups.. Based on the available evidence, phytoestrogen supplements have a safe side-effect profile with moderately elevated rates of gastrointestinal side effects. Rates of vaginal bleeding, endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly increased among phytoestrogen users in the investigated studies.

Topics: Breast Neoplasms; Dietary Supplements; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Endometrial Hyperplasia; Endometrial Neoplasms; Estrogen Replacement Therapy; Female; Follow-Up Studies; Gastrointestinal Diseases; Humans; Incidence; Phytoestrogens; Plant Extracts; Postmenopause; Randomized Controlled Trials as Topic; Risk Assessment; Uterine Hemorrhage

This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.

Topics: 4-Butyrolactone; Animals; Cardiovascular Diseases; Colorectal Neoplasms; Dietary Fiber; Edible Grain; Endometrial Neoplasms; Feeding Behavior; Female; Health Status; Humans; Isoflavones; Lignans; Male; Phytoestrogens; Plants, Edible; Prostatic Neoplasms; Seeds; Vegetables

Interest in the physiological role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the class of compounds known as the phytoestrogens, which embody several groups of non-steroidal oestrogens including isoflavones & lignans that are widely distributed within the plant kingdom. Data from animal and in vitro studies provide plausible mechanisms to explain how phytoestrogens may influence hormone dependent states, but although the clinical application of diets rich in these oestrogen mimics is in its infancy, data from preliminary studies suggest potential beneficial effects of importance to health. Phytoestrogens are strikingly similar in chemical structure to the mammalian oestrogen, oestradiol, and bind to oestrogen receptors (ER) with a preference for the more recently described ER beta. This suggests that these compounds may exert tissue specific effects. Numerous other biological effects independent of the ER (e.g. antioxidant capacity, antiproliferative and antiangiogenic effects) have been ascribed to these compounds. Whether phytoestrogens have any biological activity in humans, either hormonal or non hormonal is a contentious issue and there is currently a paucity of data on human exposure. Much of the available data on the absorption and metabolism of dietary phytoestrogens is of a qualitative nature; it is known that dietary phytoestrogens are metabolised by intestinal bacteria, absorbed, conjugated in the liver, circulated in plasma and excreted in urine. Recent studies have addressed quantitatively what happens to isoflavones following ingestion--with pure compound and stable isotope data to compliment recent pharmacokinetic data for soy foods. The limited studies conducted so far in humans clearly confirm that soya isoflavones can exert hormonal effects. These effects may be of benefit in the prevention of many of the common diseases observed in Western populations (such as breast cancer, prostate cancer, menopausal symptoms, osteoporosis) where the diet is typically devoid of these biologically active naturally occurring compounds. However since biological effects are dependent on many factors including dose, duration of use, protein binding affinity, individual metabolism and intrinsic oestrogenic state, further clinical studies are necessary to determine the potential health effects of these compounds in specific population groups. However we cur

Topics: Animals; Breast Neoplasms; Coronary Disease; Diet; Endometrial Neoplasms; Estrogens, Non-Steroidal; Female; Humans; Infant; Infant Food; Intestinal Absorption; Isoflavones; Lignans; Male; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Premenopause; Risk Factors

Environmental oestrogens have been implicated in the pathogenesis of hormonally treated cancers (such as breast and prostate cancer), male infertility, and abnormalities of the male and female reproductive tracts. They may be derived from plants (phytoestrogens), pharmaceuticals, or other synthetic compounds not originally intended to have oestrogenic activity (including soy based infant formulas). This review will discuss the evidence from both animal studies and humans for an effect of these ubiquitous compounds on the development of the human female genital tract, in addition to prolonging the menstrual cycle, alleviating symptoms of the menopause, and protecting against the development of endometrial carcinoma.

Topics: Endometrial Neoplasms; Environmental Exposure; Estrogens, Non-Steroidal; Female; Genitalia, Female; Humans; Isoflavones; Menopause; Menstrual Cycle; Phytoestrogens; Plant Preparations

Topics: Breast Neoplasms; Endometrial Neoplasms; Epidemiologic Studies; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Lung Neoplasms; Male; Neoplasms; Neoplasms, Hormone-Dependent; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Risk Factors; Stomach Neoplasms

Topics: Animals; Bone Density; Breast Neoplasms; Cognition; Coronary Disease; Endometrial Neoplasms; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Osteoporosis; Patient Compliance; Phytoestrogens; Plant Preparations; Risk Assessment; Soybean Proteins; Treatment Outcome

Although there is evidence that phytochemicals decrease the incidence of breast and endometrial cancer, many observations are only phenomenologic, and much work needs to be done to explore basic mechanisms and the strategic exploitation of their interactions. The multiplicity of phytochemical actions at different sites in the process of tumorigenesis may eventually lead to the development of a multiagent strategy designed to maximize the complementary effects of different agents. A number of effects with possible relevance to cancer chemoprevention have been excluded from this review, including effects of phytochemicals on the immune response; the question of dietary restriction, which has a profound effect on tumorigenesis; the relatively low methionine levels in some phytochemicals such as soy, which may limit the synthesis of polyamines necessary for tumor growth [151]; and the fact that diets higher in plant products are usually lower in fat and result in leaner individuals with less potential for the synthesis of estradiol in adipose tissue. Also, many studies dealing solely with in vitro mutagenesis were excluded.

Topics: Amino Acid Sequence; Anticarcinogenic Agents; Antineoplastic Agents, Hormonal; Antioxidants; Apoptosis; Breast Neoplasms; Carotenoids; Cell Differentiation; Diet; Endometrial Neoplasms; Enzyme Inhibitors; Estrogens, Non-Steroidal; Ethnicity; Female; Gene Expression Regulation; Growth Inhibitors; Humans; Isoflavones; Molecular Sequence Data; Phytoestrogens; Plant Preparations; Plants, Edible; Terpenes

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Diet, Vegetarian; Dietary Fats; Dietary Fiber; Endometrial Neoplasms; Estrogens; Estrogens, Non-Steroidal; Female; Gonadal Steroid Hormones; Humans; Incidence; Isoflavones; Lignans; Lignin; Male; Menopause; Ovarian Neoplasms; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Risk Factors

This study aims to determine whether long-term isoflavone soy protein (ISP) supplementation affects endometrial thickness and rates of endometrial hyperplasia and cancer in postmenopausal women.. In this randomized, double-blind, placebo-controlled trial, 350 postmenopausal women aged 45 to 92 years were randomized to a total daily dose of 154 mg of ISP or a milk protein-matched placebo for a 3-year period. Women with a surgically absent uterus were excluded from the analysis (final study population, N = 224). The main outcome measures were as follows: mean change in endometrial thickness on transvaginal ultrasound from baseline until up to 36 months of follow-up and the incidence of endometrial sampling, endometrial hyperplasia, and endometrial cancer.. A total of 666 visits among 224 participants were evaluated. Treatment groups did not significantly differ on the mean baseline or on-trial changes in endometrial thickness. Of the 103 placebo-treated participants, 7 (6.8%) underwent endometrial biopsy; 6 (85.7%) of these biopsies were benign. One woman in the placebo group was diagnosed with complex endometrial hyperplasia with atypia and underwent hysterectomy. The pathology result from this surgical operation was stage IB endometrial cancer. Of the 121 participants in the soy group, 9 (7.4%) underwent endometrial biopsy. The results were benign in all nine cases (100%). Although the rate of hyperplasia/malignancy was higher in the placebo group (14.3% vs 0%), the difference was not statistically significant.. Three-year ISP supplementation has no effect on endometrial thickness or on the rates of endometrial hyperplasia and cancer in postmenopausal women.

Topics: Aged; Aged, 80 and over; Biopsy; Dietary Supplements; Double-Blind Method; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Isoflavones; Middle Aged; Phytoestrogens; Placebos; Postmenopause; Risk Factors; Soybean Proteins; Ultrasonography

Phytoestrogens are plant-derived compounds that are structurally similar to endogenous estrogens. Studies have shown phytoestrogens to have possible health benefits although they could also act as endocrine disruptors. This is particularly relevant for estrogen-dependent cancers since estrogens increase risk of breast, endometrial, and ovarian cancer. Using data from the National Health and Nutritional Examination Survey (NHANES), we assessed the associations between urinary phytoestrogens (daidzein, equol, o-Desmethylangolensin (O-DMA), genistein, enterodiol, enterolactone) and breast, endometrial, and ovarian cancer using multivariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs). Cancer diagnosis and other characteristics were collected via in-person questionnaires. We found women in the highest tertile for daidzein and enterodiol had over twice the odds of having breast cancer (OR = 2.51, 95% CI 1.44-4.36 for daidzein, OR = 2.78, 95% CI 1.44-5.37 for enterodiol). In addition, women in the highest tertiles for daidzein and genistein had three to four times the odds of having endometrial cancer, respectively (OR = 3.09, 95% CI 1.01-9.49 for daidzein, OR = 4.00, 95% CI 1.38-11.59 for genistein). Overall, phytoestrogens were positively associated with breast and endometrial cancer although the associations varied by phytoestrogen type. Additional studies are needed to further inform phytoestrogens' role in disease etiology.Supplemental data for this article is available online at at https://doi.org/10.1080/01635581.2021.2020304.

Topics: Breast Neoplasms; Endometrial Neoplasms; Estrogens; Female; Genistein; Humans; Isoflavones; Lignans; Nutrition Surveys; Ovarian Neoplasms; Phytoestrogens

To further define the utility of the Ishikawa cells as a reliable in vitro model to determine the potential estrogenic activity of chemicals of interest, transcriptional changes induced by genistein (GES) in Ishikawa cells at various doses (10 pM, 1 nM, 100 nM, and 10 μM) and time points (8, 24, and 48 h) were identified using a comprehensive microarray approach. Trend analysis indicated that the expression of 5342 unique genes was modified by GES in a dose- and time-dependent manner (P ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest dose of GES evaluated (10 μM). The GES' estrogenic activity was identified by comparing the Ishikawa cells' response to GES versus 17 α-ethynyl estradiol (EE, at equipotent doses, ie, 10 μM vs 1 μM, respectively) and was defined by changes in the expression of 284 unique genes elicited by GES and EE in the same direction, although the magnitude of the change for some genes was different. Further, comparing the response of the Ishikawa cells exposed to high doses of GES and EE versus the response of the juvenile rat uterus exposed to EE, we identified 66 unique genes which were up- or down regulated in a similar manner in vivo as well as in vitro Genistein elicits changes in multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response and offer an in vitro model to assess this mode of action.

Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Dose-Response Relationship, Drug; Endometrial Neoplasms; Estradiol; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genistein; Humans; Oligonucleotide Array Sequence Analysis; Phytoestrogens; Rats; Transcription, Genetic; Uterus

Topics: Endometrial Neoplasms; Feeding Behavior; Female; Glycine max; Humans; Isoflavones; Phytoestrogens; Soy Foods

Compared with western populations, the consumption of soy foods among Japanese is very high and the incidence of endometrial cancer very low. We evaluated the association of soy food and isoflavone intake with endometrial cancer risk in Japanese women.. Prospective cohort study.. Ten public health centre areas in Japan.. Forty nine thousand one hundred and twenty-one women of age 45-74 years who responded to a 5-year follow-up survey questionnaire.. Intakes of soy foods as well as other covariates were assessed in 1995-1998 by a self-administered food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).. Incidence of endometrial cancer.. During an average of 12.1 years of follow up, 112 newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes of soy food and isoflavone were not associated with the risk of endometrial cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy food was 1.02 (95% CI 0.94-1.10), and the corresponding value for isoflavone intake per 15 mg/day was 1.01 (95% CI 0.84-1.22).. In this population-based prospective cohort study of Japanese women, we observed no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk.

Topics: Aged; Body Mass Index; Diet Surveys; Endometrial Neoplasms; Feeding Behavior; Female; Follow-Up Studies; Glycine max; Humans; Isoflavones; Japan; Middle Aged; Phytoestrogens; Population Surveillance; Proportional Hazards Models; Prospective Studies; Public Health; Risk Factors; Soy Foods; Surveys and Questionnaires

Blackcurrants (Ribes nigrum L., Grossulariaceae) contain high amounts of anthocyanin polyphenols, which have antioxidant and anti-carcinogenic health benefits. This study analyzed the potential phytoestrogenic effects of blackcurrant extract (BCE) in breast cancer (MCF-7) and human endometrial cancer (Ishikawa) cell lines that over-express estrogen receptor alpha (ERα), as well as in immature female rats.. Microarray analysis and Ingenuity® Pathway Analysis showed that BCE activated the ERα pathway, whereas quantitative-PCR confirmed that BCE and four types of anthocyanins up-regulated genes downstream of ERα. BCE (0.1-1.0 μg/mL) and anthocyanins (0.1-10 μM) induced MCF-7 cell proliferation; however, this effect was blocked by ER antagonist fulvestrant. Flow cytometry showed that anthocyanins reduced and increased the number of MCF-7 cells in the G0/G1 and G2/M phases, respectively. Anthocyanins stimulated ERα transcriptional activity in human ERα reporter assays and induced alkaline phosphatase activity in Ishikawa cells. Competition assays and in silico analysis indicated that anthocyanins bind to ERα. Finally, BCE focally induced stratification of columnar epithelial cells in the rat uterus and increased cytoplasmic mucin levels in these cells.. These results suggest that blackcurrant anthocyanins act as phytoestrogens in vitro and in vivo.

Topics: Alkaline Phosphatase; Animals; Anthocyanins; Binding, Competitive; Cell Cycle; Cell Line, Tumor; Endometrial Neoplasms; Estrogen Receptor beta; Female; Gene Expression Profiling; Humans; MCF-7 Cells; Molecular Docking Simulation; Phytoestrogens; Rats, Sprague-Dawley; Ribes

Estrogen replacement therapy is commonly used to replace the loss of estrogen in post-menopausal women. However, it is not suitable to be used in women taking tamoxifen as both of the drugs increase the risk of endometrial cancer. This project aimed to study the potential of using the natural compound glabridin in combination with tamoxifen as a drug for estrogen replacement therapy. Ishikawa and MCF-7 cells were used to investigate the estrogenic activities stimulated by the combination of tamoxifen and glabridin through ALP and MTT assays. The expressions of the ESR1 and bcl-2 genes have also been determined using RT-PCR. The results indicated that the combination of 1 x 10(-5)M tamoxifen and 1 x 10(-6)M glabridin exhibited estrogenic activities and suppressed cell growth in both cell lines. The relative expressions of ESR1 and bcl-2 genes indicated that the estrogenicity expressed by the combinatory drug was regulated by estrogen receptor a; however, the reduction in cell proliferation was not modulated by bcl-2 anti-apoptotic proteins. These results suggested that the combination of tamoxifen and glabridin has potential to be used as an estrogen replacement drug with a reduced risk of endometrial cancer that has arisen from the intake of tamoxifen.

Topics: Adenocarcinoma; Breast Neoplasms; Cell Line, Tumor; Drug Therapy, Combination; Endometrial Neoplasms; Estrogens; Female; Humans; Isoflavones; Phenols; Phytoestrogens; Selective Estrogen Receptor Modulators; Tamoxifen

The present study aimed to investigate whether genistein, a potent phytoestrogen mainly found in soybean, modulated the expression of TLRs 2, 3, 4 and 9 proteins in human endometrial epithelial cell line RL95-2 under basal and polyinosinic-polycytidylic acid (poly I: C) stimulated conditions to mimic viral infection. The genistein effects were also compared with 17β-estradiol.. The RL95-2 cells were cultured in the estrogen-deprived media with or without poly I: C 30 min prior to incubation with genistein (10(-7), 10(-6) or 10(-5) M) or 17β-estradiol (10(-9) M) for 48 h. The TLRs protein expression was analyzed by semi-quantitative Western blot.. The cells expressed TLRs 3, 4 and 9 but a very low level of TLR2 proteins. Poly I: C significantly increased the TLRs 2 and 9 protein expressions whereas the TLRs 3 and 4 were reduced. Under basal condition, genistein at 10(-7) M increased the TLR2 while 17β-estradiol decreased the TLR4. All concentrations of genistein and 17β-estradiol attenuated the poly I: C induced increase in the TLR2. By contrast, both genistein at 10(-5) M and 17 β-estradiol further potentiated the TLR4 suppressed by poly I: C. Only 17β-estradiol was found to antagonize the poly I: C-induced changes in TLRs 3 and 9.. Taken together, the present results that genistein increased the basal TLR2 and attenuated the viral component-induced TLR2 protein expression in human endometrial epithelial cells may indicate the potential role of this soy isoflavone in promoting the uterine immune function and probably alleviating the inflammation of endometrium following pathogen

Topics: Blotting, Western; Cell Line; Endometrial Neoplasms; Endometrium; Epithelial Cells; Estradiol; Female; Genistein; Humans; Phytoestrogens

Phyto-oestrogens have been suggested to have a protective effect on hormone-sensitive cancers. However, few studies have investigated the association between dietary phyto-oestrogens and gynaecological cancers. In the present study, we analysed data from two population-based case-control studies of ovarian (1366 cases and 1414 controls) and endometrial (1288 cases and 1435 controls) cancers. Dietary intake information was obtained using a 135-item FFQ, and phyto-oestrogen intake was estimated using published food composition databases. Unconditional logistic regression was used to estimate adjusted OR and 95% CI. In multivariable analyses, there was a suggestive pattern of inverse associations between increasing intakes of total phyto-oestrogens, isoflavones and enterolignans and the risk of ovarian cancer. However, the results only reached statistical significance for the lignan compounds matairesinol and lariciresinol, where the OR for the highest v. the lowest intake category was 0.72 (95% CI 0.54, 0.96; P for trend = 0.02) for matairesinol and 0.72 (95% CI 0.55, 0.96; P for trend = 0.03) for lariciresinol. When the risk of ovarian cancer was assessed by subtype, there was an indication that increasing intakes of phyto-oestrogens may be associated with a decreased risk of mucinous (cases n 158) ovarian tumours (OR for the highest v. the lowest intake category: 0.47 (95% CI 0.24, 0.93); P for trend = 0.04). However, there were no significant associations with other histological subtypes. In contrast, dietary phyto-oestrogens (total or any subclass) were unrelated to the risk of endometrial cancer cases overall or by subtype.

Topics: Adenocarcinoma, Mucinous; Aged; Australia; Case-Control Studies; Diet; Diet Surveys; Endometrial Neoplasms; Female; Furans; Humans; Isoflavones; Lignans; Lignin; Logistic Models; Middle Aged; Odds Ratio; Ovarian Neoplasms; Phytoestrogens; Surveys and Questionnaires

The phyto-oestrogen enterolactone has been hypothesised to protect against hormone-dependent cancers, probably through its antioestrogenic potential. We investigated whether a higher level of plasma enterolactone was associated with a lower incidence of endometrial cancer in a case-cohort study in the ‘Diet, Cancer and Health’ cohort. The cohort study included 29 875 women aged 50–64 years enrolled between 1993 and 1997. Information on diet and lifestyle was provided by self-administrated questionnaires and blood was drawn from each participant. Time-resolved fluoroimmunoassay was used for biochemical determination of plasma enterolactone. A total of 173 cases and 149 randomly selected cohort members were included. We estimated incidence rate ratio (IRR) and 95% CI by a Cox proportional hazards model. A 20 nmol/l higher plasma concentration of enterolactone was associated with a non-significant lower risk of endometrial cancer (IRR 0.93, 95% CI 0.84, 1.04). When excluding women with low enterolactone concentrations (quartile 1) due to potential recent antibiotic use, the association became slightly stronger, but remained non-significant (IRR 0.90, 95% CI 0.79, 1.02). Menopausal status, hormone replacement therapy or BMI did not modify the association. In conclusion, we found some support for a possible inverse association between plasma enterolactone concentration and endometrial cancer incidence.

Topics: 4-Butyrolactone; Cohort Studies; Denmark; Diet Surveys; Endometrial Neoplasms; Female; Fluoroimmunoassay; Hormone Replacement Therapy; Humans; Incidence; Lignans; Middle Aged; Phytoestrogens; Proportional Hazards Models; Surveys and Questionnaires

Cytochrome c (CytC) released from mitochondria induces apoptosis in both normal and tumor cells. Expression of Fas ligand (FasL) helps maintain tumor cell survival by inducing apoptosis of Fas-bearing anti-tumor immune cells. A risk of endometrial cancer has been reported to associate with phytoestrogen consumption. Therefore the effects of phytoestrogens, genistein and daidzein, on FasL and CytC protein expression were examined in primary cultured porcine endometrial cells (PE) and human cancerous endometrial cells (RL95-2) by Western blot analysis. Both cells were cultured in standard medium (SM) and switched to estrogen-deprived medium (SF) with or without 17beta-estradiol (E, 1 nM), genistein (10 microM) or daidzein (10 microM) for 48 h. FasL (25 kDa) which was found only in RL95-2 cells was upregulated in SF compared to SM. Treatment of RL95-2 cells with E, daidzein or genistein significantly increased the FasL expression by 7-10 folds. In the present study, low level of CytC was detected in both cells cultured in SM but markedly increased in SF by 1.5-2 folds. The SF-induced increase in CytC level was reversed by genistein or daidzein while E suppressed CytC in PE cells, but not in RL95-2 cells. The findings suggest that genistein and daidzein appear to act as a survival factor by inhibiting intracellular apoptogenic initiator in both normal and cancer endometrial cells. In addition, estrogen and phytoestrogens inducing the death signal FasL expressed by cancerous endometrial cells may cause the tumor progression. Thus, consuming phytoestrogen as a supplement should be awareness in patient with endometrial cancer.

Topics: Analysis of Variance; Animals; Apoptosis; Blotting, Western; Cells, Cultured; Cytochromes c; Endometrial Neoplasms; Estradiol; Fas Ligand Protein; Female; Genistein; Humans; Isoflavones; Phytoestrogens; Swine

Phytochemicals found in soy and other legumes have been speculated to reduce the risk of endometrial cancer; however, inconsistent findings have been reported in the few epidemiological studies conducted to date.. We conducted a prospective analysis of 46 027 nonhysterectomized postmenopausal women who were recruited into the Multiethnic Cohort (MEC) Study between August 1993 and August 1996 and provided detailed baseline information on diet and other endometrial cancer risk factors. A total of 489 women diagnosed with incident endometrial cancer were identified through the Surveillance, Epidemiology, and End Results tumor registry linkages during a median follow-up period of 13.6 years. Cox proportional hazards models were used to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with dietary intake of legumes, soy, and tofu, and for total isoflavones and specific isoflavones (daidzein, genistein, or glycitein). Truncated (age 50-89 years) age-adjusted incidence rates were calculated by applying age-specific rates within isoflavone quintiles to the overall MEC population eligible for endometrial cancer. To estimate the percentage of endometrial cancers that may have been prevented by consuming the highest quintile of total isoflavones, the partial population attributable risk percent was calculated.. A reduced risk of endometrial cancer was associated with total isoflavone intake (highest vs lowest quintile, ≥7.82 vs <1.59 mg per 1000 kcal/d, RR = 0.66, 95% CI = 0.47 to 0.91), daidzein intake (highest vs lowest quintile, ≥3.54 vs <0.70 mg per 1000 kcal/d, RR = 0.64, 95% CI = 0.46 to 0.90), and genistein intake (highest vs lowest quintile, ≥3.40 vs <0.69 mg per 1000 kcal/d, RR = 0.66, 95% CI = 0.47 to 0.91). No statistically significant association with endometrial cancer risk was observed for increasing intake of legumes, soy, tofu, or glycitein. Truncated age-adjusted incidence rates of endometrial cancer for the highest vs lowest quintile of total isoflavone intake were 55 vs 107 per 100 000 women per year, respectively. The partial population attributable risk percent for total isoflavone intake lower than the highest quintile was 26.7% (95% CI = 5.3% to 45.8%).. This study suggests that greater consumption of isoflavone-containing foods is associated with a reduced risk of endometrial cancer in this population of nonhysterectomized postmenopausal women.

Topics: Aged; Aged, 80 and over; Cohort Studies; Endometrial Neoplasms; Fabaceae; Feeding Behavior; Female; Genetic Predisposition to Disease; Genistein; Glycine max; Growth Inhibitors; Humans; Incidence; Isoflavones; Life Style; Middle Aged; Phytoestrogens; Postmenopause; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; SEER Program; Soy Foods; Surveys and Questionnaires; United States

Our research is focused on modifying effects of an isoflavone aglycones (IAs)-rich extract at a hormonally active dose of 150 mg/kg body weight/day on mammary and endometrial carcinogenesis in female Donryu rats. IA administered for 2 weeks in a phytoestrogen-low diet exerted estrogenic activity and induced cell proliferation in the uterus of ovariectomized rats. Furthermore, administration for 4 weeks resulted in elevation of cell proliferation in the mammary glands of 7,12-dimethylbenz[a]anthracene (DMBA)-treated animals. Forty weeks of postpubertal administration of IA to 5-week-old rats after initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) caused significant increase of incidence and multiplicity of mammary adenocarcinoma, multiplicities of endometrial atypical hyperplasia, adenomatous polyps, and an increased trend of uterine adenocarcinomas. Liquid chromatography with tandem mass spectrometry and immunohistochemical analyses revealed significant elevation of tumorigenesis-related proteins such as S100 calcium-binding protein A8, kininogen 1, and annexins 1 and 2 in mammary adenocarcinomas and cadherin EGF LAG seven-pass G-type receptor 2, DEAD box polypeptide 1, and cysteine- and glycine-rich protein 1 in uterine proliferative lesions of IA-treated animals. Those changes are likely to be related to modulation of estrogen receptor (ER), AP1, nuclear factor-kappa B, and actin signaling pathways. Our results indicate that the postpubertal exposure of Donryu rats to IA at an estrogenic dose results in promotion of mammary and uterine carcinogenesis induced by DMBA and ENNG, which might be related to the activation of ER-dependent signaling and alteration of the molecular tumor environment in the mammary gland and endometrium.

Topics: Adenocarcinoma; Aging; Animals; Cell Proliferation; Cocarcinogenesis; Dietary Supplements; Endometrial Neoplasms; Extracellular Matrix Proteins; Female; Isoflavones; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Neoplasm Proteins; Ovariectomy; Phytoestrogens; Plant Extracts; Rats; Rats, Inbred Strains; Tumor Burden; Uterus

To determine whether the prescribing practice of physicians with regard to estrogen replacement therapy (ERT) in symptomatic women with previous endometrial cancer is consistent with the available evidence.. A descriptive survey was conducted among physicians in Germany, using a questionnaire containing two hypothetical cases of endometrial cancer patients ('low-risk' and 'high-risk' disease) and menopausal symptoms. Physicians were asked about their prescribing practice concerning moderate to severe menopausal symptoms.. Four hundred and twenty questionnaires were sent out, with an overall response rate of 39.8%; 45.6% in the 'low-risk' case and 75.4% in the 'high-risk' case (p < 0.0001) stated that ERT is contraindicated. Only 12.9% were willing to prescribe ERT; 81.9% preferred to prescribe non-estrogenic alternatives (44.8% phytoestrogens, 29.0% selective serotonin reuptake inhibitors).. Despite the evidence that ERT does not increase the risk of recurrence of endometrial cancer, many physicians are reluctant to prescribe ERT in women suffering from moderate to severe menopausal symptoms.

Topics: Adenocarcinoma; Attitude of Health Personnel; Contraindications; Endometrial Neoplasms; Estrogen Replacement Therapy; Female; Germany; Hot Flashes; Humans; Libido; Menopause; Phytoestrogens; Practice Patterns, Physicians'; Risk Assessment; Selective Serotonin Reuptake Inhibitors; Surveys and Questionnaires

Phytoestrogens have been shown to exert anti-estrogenic and estrogenic effects in some tissues, including the breast. However, only a few studies have evaluated their role in endometrial cancer risk. We evaluated this association in a population-based case-control study in New Jersey. A total of 424 cases and 398 controls completed an interview, including a food frequency questionnaire with supplemental questions for phytoestrogen foods. Risk estimates were derived using an unconditional logistic regression, adjusting for major risk factors for endometrial cancer. There was some suggestion of a decreased risk with quercetin intake (OR: 0.65; 95% CI: 0.41-1.01 for the highest compared to the lowest quartile; p for trend: 0.02). We found a limited evidence of an association with any of the lignans evaluated, total lignans, coumestrol, individual isoflavones, total isoflavones, or total phytoestrogens. However, there was some suggestion of an inverse association with total isoflavone intake limited to lean women (BMI <25; OR for the highest tertile: 0.50; 95% CI: 0.25-0.98) and those with a waist-to-hip ratio

Topics: Aged; Body Mass Index; Case-Control Studies; Coumestrol; Eating; Endometrial Neoplasms; Estrogen Replacement Therapy; Female; Food; Humans; Interviews as Topic; Isoflavones; Lignans; Middle Aged; New Jersey; Phytoestrogens; Quercetin; Risk Factors; Soy Foods; Waist-Hip Ratio

Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (diethylstilbestrol, genistein, zearalenone, resveratrol, bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused by these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, bisphenol A, o,p'-DDT, zearalenone, genistein and resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects.

Topics: Benzhydryl Compounds; Cell Line, Tumor; Cluster Analysis; DDT; Diethylstilbestrol; Endocrine Disruptors; Endometrial Neoplasms; Estradiol; Estrogen Antagonists; Estrogens; Female; Fulvestrant; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genistein; Humans; Oligonucleotide Array Sequence Analysis; Phenols; Phytoestrogens; Polymerase Chain Reaction; Receptors, Estrogen; Reproducibility of Results; Resveratrol; Risk Assessment; RNA, Messenger; Stilbenes; Time Factors; Zearalenone

This study examines the association between dietary patterns and endometrial cancer risk. A case-control study of endometrial cancer was conducted from 1996 to 1999 in the San Francisco Bay Area in white, African-American, and Latina women age 35-79. Dietary patterns were defined using a principal components analysis; scoring dietary intake based on correspondence to a Mediterranean-style diet; and by jointly categorizing intake of fruits/vegetables and dietary fat. Four dietary patterns were identified and labeled "plant-based," "western," "ethnic," and "phytoestrogen-rich." None of these dietary patterns nor adherence to a Mediterranean diet (to the extent consumed by this population) was associated with endometrial cancer risk. However, among non-users of supplements, greater consumption of the "western" dietary pattern was associated with a 60% increase in risk (95% CI: 0.95-2.7 per unit change; P-interaction = 0.10). A diet characterized by high fat consumption increased risk, regardless of fruit and vegetable consumption (OR = 1.4, 95% CI: 0.97-2.1 for high fat, low fruit/vegetable intake and OR = 1.4, 95% CI: 0.95-2.1 for high fat, high fruit/vegetable intake compared to low fat, high fruit/vegetable intake). Thus, while like others we found that dietary fat increases endometrial cancer risk, the evaluation of dietary patterns did not provide any additional information regarding risk.

Topics: Adult; Aged; Case-Control Studies; Confidence Intervals; Diet; Diet, Mediterranean; Dietary Fats; Dietary Fiber; Dietary Proteins; Endometrial Neoplasms; Ethnicity; Female; Fruit; Humans; Interviews as Topic; Logistic Models; Middle Aged; Odds Ratio; Phytoestrogens; Plant Preparations; Plants, Edible; Postmenopause; Premenopause; Principal Component Analysis; Risk Factors; Surveys and Questionnaires; Vegetables

Human endometrial carcinomas, as well as complex atypical hyperplasias (CAH), are estrogen related and frequently have mutations in the PTEN gene. However, the mutual contribution of estrogen and PTEN mutations to endometrial carcinogenesis in vivo is unknown. To address this issue, we investigated whether neonatal estrogenic treatments augment the incidence of CAH and carcinomas in murine PTEN (mPTEN) heterozygous (+/-) mutant mice, an animal model for endometrial carcinoma. Low doses of diethylstilbestrol (1 ng/g/day), genistein (50 microg/g/day) in phytoestrogens, estriol (E(3)) (4 microg/g/day), and vehicle (ethanol and corn oil) were administered subcutaneously daily to neonatal pups from the 1st to 5th day after birth. At 52 weeks of age, the morphological changes in the endometrium, and uterine expression of Hoxa 10 and Hoxa 11, were evaluated. These Hoxa genes are abdominal B-type homeobox genes, which normally regulate differentiation of the Müllerian duct. The incidence of CAH and adenocarcinomas of the endometrium was significantly decreased by the neonatal estrogenic treatments in the mPTEN+/- mice. Coincidentally, all treatments significantly decreased the stromal cell density, and CAH and adenocarcinomas rarely developed in the epithelium adjacent to the affected endometrial stroma. Moreover, the uterine expression of Hoxa 10 in mice with neonatal genistein and E(3) treatments, and that of Hoxa 11 in mice with all treatments, was significantly lower when compared with vehicle alone. Taken together, neonatal estrogenic exposure induced stromal atrophy and/or hyalinization accompanied by repressed expression of Hoxa 10 and Hoxa 11, and exerted an inhibitory effect on PTEN-related tumorigenesis. These findings provide new insight into the interaction between endometrial epithelium and stroma in endometrial carcinogenesis in vivo.

Topics: Adenocarcinoma; Animals; Animals, Newborn; Disease Models, Animal; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Homeobox A10 Proteins; Homeodomain Proteins; Mice; Mice, Inbred C57BL; Organ Size; Phytoestrogens; PTEN Phosphohydrolase; Recombination, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Uterus

To document the chemical and biologic profile of a clinical phase II red clover (Trifolium pratense L.) extract by identifying and measuring the major and minor components visible in the high-performance liquid chromatography-ultraviolet (HPLC-UV) chromatogram and evaluating each compound for estrogenic and antioxidant activity.. Individual compounds in the preformulated (i.e., no excipients present) extract were identified by either chemical isolation followed by structure elucidation or matching to retention time and molecular mass of chemical standards via liquid chromatography-mass spectrometry (LC-MS) analysis. Quantitation of the amounts of compounds found in the preformulated extract was done using HPLC-UV or LC-MS. Isolated compounds or standards were evaluated for their ability to: (1) induce alkaline phosphatase (AP) in an endometrial carcinoma cell line, (2) competitively bind to recombinant human estrogen receptors (ERs) alpha (alpha) and beta (beta), and (3) act as antioxidants by scavenging 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) free radicals.. The preformulated red clover extract had 50% effective concentration (EC 50) of 2.0 to 2.2 microg/mL in the AP estrogenicity assay, and 50% inhibitory concentrations (IC(50)s) of 18.4 to 32.6 microg/mL and 1.9 to 3.4 microg/mL in the ERalpha and ERbeta binding assays, respectively. The preformulated extract was composed of 35.54% isoflavones, 1.11% flavonoids, 0.06% pterocarpans, < or =0.03% coumarins, and < or =0.03% tyramine. Daidzein, genistein, formononetin, biochanin A, coumestrol, and naringenin were estrogenic in the AP assay, and all of these, except formononetin, bound to one or both ERs.. The major and minor chemical and active estrogenic components of a preformulated phase II red clover clinical extract were identified, quantitatively measured, and the final capsule doses were calculated. The extract is currently under evaluation in a year-long clinical study for the alleviation of menopausal hot flashes. This is the first report to thoroughly summarize the chemistry and biology of all major peaks observed in the HPLC-UV chromatogram of a clinical red clover dietary supplement.

Topics: Alkaline Phosphatase; Cell Division; Cell Line, Tumor; Chromatography, High Pressure Liquid; Clinical Trials, Phase II as Topic; Endometrial Neoplasms; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Humans; Isoflavones; Phytoestrogens; Plant Extracts; Trifolium

The aim of this study was to identify genomic aberrations in endometrial cancer cells treated with the phyto-estrogenic compounds tectorigenin, irigenin and apigenin and to compare with those treated with beta-estradiol using array-based comparative genomic hybridisation (array CGH). The microarray contains 287 targets and includes telomeres, microdeletions, oncogenes and tumour suppressor genes and has increased mapping resolution compared to conventional CGH. An endometrial cancer cell line (Ishikawa) was cultured and treated with the phyto-estrogens. Treated cells were examined using the CGH microarray. Over 20 % of the array genes were aberrated in the cells treated with beta-estradiol, tectorigenin and irigenin compared to 3 % in those treated with the same concentration of apigenin. Protein kinase c zeta form, insulin, insulin receptor and protein-tyrosine phosphatase non-receptor-type 1 which are involved in insulin metabolism were aberrated by tectorigenin and irigenin. Apigenin may play a role in the treatment of endometrial cancer and in the treatment of postmenopausal women. Further studies in normal endometrium and primary endometrial cancer cells are needed to elucidate the role of the phyto-estrogens.

Topics: Apigenin; Cell Line, Tumor; Chromosome Aberrations; DNA, Neoplasm; Endometrial Neoplasms; Estradiol; Female; Gene Expression Profiling; Humans; Iridaceae; Isoflavones; Phytoestrogens; Phytotherapy; Plant Extracts; RNA, Messenger

The soy isoflavone daidzein (DAI) is known to undergo metabolism to equol (EQO) and to 3'-hydroxy-DAI (3'-HO-DAI) and 6-hydroxy-DAI (6-HO-DAI) in humans. In order to better understand the implications of soy diets for human health, the hormonal and genotoxic activities of these DAI metabolites were studied in cultured human endometrial carcinoma cells. When the estrogenicity was tested by cell-free binding to recombinant human estrogen receptor (ER) alpha and beta as well as by the induction of enzyme activity and gene expression of alkaline phosphatase (ALP) in Ishikawa cells, the ranking order was EQO>DAI>3'-HO-DAI>6-HO-DAI. All compounds had a higher affinity to ERbeta than to ERalpha. No significant anti-estrogenic effects of the DAI metabolites were observed in the cells at non-cytotoxic concentrations. The in vitro genotoxicity was assessed by analyzing effects on cell cycle distribution and cell morphology as well as the induction of micronuclei (MN). EQO caused a slight increase in G1 and decrease in S phase of the cell cycle, and slightly but significantly induced kinetochore-positive as well as kinetochore-negative MN and an elevated proportion of abnormal mitotic spindles. 3'-HO-DAI, but not 6-HO-DAI, induced kinetochore-negative MN. The observation that major human metabolites of DAI exhibit estrogenic and genotoxic potential may be of relevance for the safety evaluation of diets containing soy isoflavones.

Topics: Adenocarcinoma; Alkaline Phosphatase; Cell Cycle; Cell Line, Tumor; Drug Screening Assays, Antitumor; Endometrial Neoplasms; Enzyme Induction; Equol; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression; Humans; Isoflavones; Micronuclei, Chromosome-Defective; Micronucleus Tests; Mutagens; Phytoestrogens; RNA, Messenger; Spindle Apparatus

To evaluate the association of intake of soya food, a rich source of phytoestrogens, with the risk of endometrial cancer.. Population based case-control study, with detailed information on usual soya food intake over the past five years collected by face to face interview using a food frequency questionnaire.. Urban Shanghai, China.. 832 incident cases of endometrial cancer in women aged of 30 to 69 years diagnosed during 1997-2001 and identified from the Shanghai Cancer Registry; 846 control women frequency matched to cases on age and randomly selected from the Shanghai Residential Registry.. Odds ratios for risk of endometrial cancer in women with different intakes of soya foods.. Regular consumption of soya foods, measured as amount of either soya protein or soya isoflavones, was inversely associated with the risk of endometrial cancer. Compared with women with the lowest quarter of intake, the adjusted odds ratio of endometrial cancer was reduced from 0.93 to 0.85 and 0.67 with increasing quarter of soya protein intake (P for trend 0.01). A similar inverse association was observed for soya isoflavones and soya fibre intake. The inverse association seemed to be more pronounced among women with high body mass index and waist:hip ratio.. Regular intake of soya foods is associated with a reduced risk of endometrial cancer.

Topics: Adult; Aged; Case-Control Studies; China; Endometrial Neoplasms; Female; Glycine max; Humans; Incidence; Isoflavones; Middle Aged; Odds Ratio; Phytoestrogens; Plant Preparations; Risk Factors; Urban Health

The development of endometrial cancer is largely related to prolonged exposure to unopposed estrogens. Phytoestrogens (i.e., weak estrogens found in plant foods) may have antiestrogenic effects. We evaluated the associations between dietary intake of seven specific compounds representing three classes of phytoestrogens (isoflavones, coumestans, and lignans) and the risk of endometrial cancer.. In a case-control study from the greater San Francisco Bay Area, we collected dietary information from 500 African American, Latina, and white women aged 35-79 years who were diagnosed with endometrial cancer between 1996 and 1999 and from 470 age- and ethnicity-matched control women identified through random-digit dialing. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).. Isoflavone (OR = 0.59, 95% CI = 0.37 to 0.93 for the highest versus lowest quartile of exposure) and lignan (OR = 0.68, 95% CI = 0.44 to 1.1) consumptions were inversely related to the risk of endometrial cancer. These associations were slightly stronger in postmenopausal women (OR = 0.44, 95% CI = 0.26 to 0.77 and OR = 0.57, 95% CI = 0.34 to 0.97 for isoflavones and lignans, respectively). Obese postmenopausal women consuming relatively low amounts of phytoestrogens had the highest risk of endometrial cancer (OR = 6.9, 95% CI = 3.3 to 14.5 compared with non-obese postmenopausal women consuming relatively high amounts of isoflavones); however, the interaction between obesity and phytoestrogen intake was not statistically significant.. Some phytoestrogenic compounds, at the levels consumed in the typical American-style diet, are associated with reduced risk of endometrial cancer.

Topics: Adult; Aged; Black or African American; Case-Control Studies; Endometrial Neoplasms; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Feeding Behavior; Female; Glycine max; Hispanic or Latino; Humans; Isoflavones; Logistic Models; Middle Aged; Obesity; Odds Ratio; Parity; Phytoestrogens; Plant Preparations; Risk Assessment; San Francisco; White People

The phytoestrogen genistein was studied in normal and malignant experimental uterine models in vivo. The action of genistein on the uterus and vagina of ovariectomized DA/Han rats after 3 day oral administration (25, 50 or 100 mg/kg/BW/d) was compared to ethinyl oestradiol (0.1 mg/kg/BW/d). Effects on uterine and vaginal morphology, uterine growth and uterine gene expression were studied. A dose dependent increase of the uterine wet weight and the uterine and vaginal epithelial height, a dose dependent up-regulation of complement C3, down-regulation of clusterin mRNA expression and a stimulation of the vaginal cornification was observed after administration of genistein. Uterine gene expression and vaginal epithelium respond to genistein at doses where no significant effects on uterine wet weight were detectable. In general the vagina was more sensitive to genistein than the uterus. To analyse the action of genistein in malignant uterine tissue, the impact of a 28 d treatment with 50 mg/kg/d of genistein on the in-vivo tumour growth of RUCA I endometrial adenocarcinoma cells, following subcutaneous inoculation into syngeneic DA/Han rats, was assessed. In contrast to ethinyl oestradiol (0.1 mg/kg/BW/d), a dose of 50 mg/kg/BW/d of genistein did not affect tumour growth. Nevertheless C3 and TRPM2 mRNA expression in the tumour were both significantly stimulated by ethinyl oestradiol and genistein. In comparison to ovariectomized animals genistein up-regulated uterine wet weight and uterine dependent gene expression in tumour bearing animals. In conclusion, four independent uterine and vaginal parameters indicate genistein is a weak oestrogen receptor agonist in the uterus and vagina of female DA/Han rats, and evidence is provided for a selective oestrogen receptor modulator (SERM)-like action of genistein in normal and malignant uterine tissue.

Topics: Adenocarcinoma; Animals; Clusterin; Complement C3; Endometrial Neoplasms; Epithelium; Estrogens, Non-Steroidal; Ethinyl Estradiol; Female; Gene Expression; Genistein; Glycoproteins; Isoflavones; Molecular Chaperones; Organ Size; Ovariectomy; Phytoestrogens; Plant Preparations; Rats; RNA, Messenger; Selective Estrogen Receptor Modulators; Tumor Cells, Cultured; Uterus; Vagina

Phytoestrogens are increasingly used by patients as "natural" alternatives to hormone replacement. Attention in scientific and lay literature has focused on their potential to prevent menopausal symptoms, bone loss, heart disease, or breast cancer. Less is known about effects on the endometrium, specifically, whether prolonged exposure to phytoestrogens could promote hyperplasia or neoplasia, as does unopposed estrogen.. We report the case of a woman diagnosed with grade 1 endometrioid adenocarcinoma of the endometrium whose history was notable for extensive use of supplemental phytoestrogens.. The effects of phytoestrogens on endometrial tissue are not known. Given their increasing popularity and availability in concentrated form as dietary supplements, additional research is warranted before we can counsel our patients regarding the safety of such supplements.

Topics: Adult; Carcinoma, Endometrioid; Dietary Supplements; Endometrial Neoplasms; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Phytoestrogens; Plant Preparations; Plants; Plants, Medicinal; Self Administration

Severe developmental and reproductive disorders in wild animals have been linked to high exposure to persistent environmental chemicals with hormonal activity. These adverse effects of environmental estrogens have raised considerable concern and have received increasing attention. Although numerous chemicals with the capacity to interfere with the estrogen receptor (ER) have been identified, information on their molecular mechanism of action and their relative potency is rather limited. For the endometrium, the lack of information is due to the lack of a suitable experimental model. We investigated the functions of phytoestrogens in an endometrial-derived model, RUCA-I rat endometrial adenocarcinoma cells. The cells were cultured on a reconstituted basement membrane to preserve their functional differentiation and estrogen responsiveness. We assessed the relative binding affinity to the estrogen receptor of the selected phytoestrogens coumestrol, genistein, daidzein, and the putative phytoestrogen mangostin compared to estradiol by a competitive Scatchard analysis. The following affinity ranking was measured: 17beta-estradiol >>> coumestrol > genistein > daidzein >>> mangostin. In addition, we investigated the capacity of these compounds to promote the increased production of complement C3, a well-known estradiol-regulated protein of the rat endometrium. All substances tested increased the production of complement C3, although different concentrations were necessary to achieve equivalent levels of induction compared to estradiol. Mechanistically we were able to demonstrate that the increase of complement C3 production was mediated by primarily increasing its steady-state mRNA level. These findings indicate that RUCA-I cells represent a sensitive model system to elucidate relative potencies and functions of environmental estrogens in an endometrium-derived model.

Topics: Adenocarcinoma; Animals; Complement C3c; Coumestrol; Endometrial Neoplasms; Endometrium; Estradiol; Estrogens, Non-Steroidal; Female; Genistein; Isoflavones; Phytoestrogens; Plant Preparations; Plants; Rats; Receptors, Estrogen; RNA, Messenger; Tumor Cells, Cultured

The authors conducted a case-control study among the multi-ethnic population of Hawaii to examine the role of dietary soy, fiber, and related foods and nutrients on the risk of endometrial cancer. Endometrial cancer cases (n = 332) diagnosed between 1985 and 1993 were identified from the five main ethnic groups in the state (Japanese, Caucasian, Native Hawaiian, Filipino, and Chinese) through the rapid-reporting system of the Hawaii Tumor Registry. Population controls (n = 511) were selected randomly from lists of female Oahu residents and matched to cases on age (+/-2.5 years) and ethnicity. All subjects were interviewed using a diet history questionnaire that included over 250 food items. Non-dietary risk factors for endometrial cancer included nulliparity, never using oral contraceptives, fertility drug use, use of unopposed estrogens, a history of diabetes mellitus or hypertension, and a high Quetelet's index (kg/cm2). Energy intake from fat, but not from other sources, was positively associated with the risk of endometrial cancer. The authors also found a positive, monotonic relation of fat intake with the odds ratios for endometrial cancer after adjustment for energy intake. The consumption of fiber, but not starch, was inversely related to risk after adjustment for energy intake and other confounders. Similar inverse gradients in the odds ratios were obtained for crude fiber, non-starch polysaccharide, and dietary fiber. Sources of fiber, including cereal and vegetable and fruit fiber, were associated with a 29-46% reduction in risk for women in the highest quartiles of consumption. Vitamin A and possibly vitamin C, but not vitamin E, were also inversely associated with endometrial cancer, although trends were not strong. High consumption of soy products and other legumes was associated with a decreased risk of endometrial cancer (p for trend = 0.01; odds ratio = 0.46, 95% confidence interval 0.26-0.83) for the highest compared with the lowest quartile of soy intake. Similar reductions in risk were found for increased consumption of other sources of phytoestrogens such as whole grains, vegetables, fruits, and seaweeds. Ethnic-specific analyses were generally consistent with these results. The observed dietary associations appeared to be largely independent of other risk factors, although the effects of soy and legumes on risk were limited to women who were never pregnant or who had never used unopposed estrogens. These data suggest that plant-based

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Confounding Factors, Epidemiologic; Dietary Fats; Dietary Fiber; Dietary Proteins; Endometrial Neoplasms; Energy Intake; Estrogens, Non-Steroidal; Ethnicity; Female; Hawaii; Humans; Isoflavones; Middle Aged; Odds Ratio; Phytoestrogens; Plant Preparations; Plants, Edible; Risk Factors; Soybean Proteins