phytoestrogens and Uterine-Neoplasms

Digoxin, a phyto-estrogen, binds with estrogen receptors (ER) and can cause gynecomastia. Among women currently using digoxin, breast and uterus cancer incidences are significantly increased (approximate risk ratios, 1.3-1.5). Both cancers are often estrogen sensitive. In contrast, ovary and cervix cancers are relatively estrogen insensitive, and incidence is unaffected by digoxin exposure. When digoxin use stops, incidence rapidly reverts to that in nonusers. These patterns parallel those of estrogen, suggesting that digoxin works via ER-stimulated proliferation of ductal and/or acinar cells, accelerating the growth of nascent cancers. Also consistent with an estrogenic effect, men using digoxin have a small but significant reduction in prostate cancer (risk ratio, 0.76). Other estrogen-like drugs, particularly spironolactone, should be investigated for similar effects. The effect of digoxin use in women being treated for breast cancer or in survivors is unknown. Women with estrogen-sensitive cancers on adjuvant therapy may take tamoxifen, which blocks ERs. However, postmenopausal patients may use aromatase inhibitors, which block estrogen production while leaving ERs susceptible to digoxin. If adverse effects are found, tamoxifen may be preferred over aromatase inhibitors in patients receiving estrogen-mimicking drugs. Alternatively, other cardiotropic drugs might be considered in women with or at high risk of developing estrogen-sensitive cancers.

Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Digoxin; Estrogens; Female; Humans; Male; Neoplasms, Hormone-Dependent; Phytoestrogens; Receptors, Estrogen; Risk Factors; Selective Estrogen Receptor Modulators; Spironolactone; Tamoxifen; Uterine Neoplasms

Studies in our laboratory have shown that exposure to genistein causes deleterious effects on the developing female reproductive system. Mice treated neonatally on days 1-5 by subcutaneous injection of genistein (0.5-50 mg/kg) exhibited altered ovarian differentiation leading to multioocyte follicles (MOFs) at 2 months of age. Ovarian function and estrous cyclicity were also disrupted by neonatal exposure to genistein with increasing severity observed over time. Reduced fertility was observed in mice treated with genistein (0.5, 5, or 25 mg/kg) and infertility was observed at 50 mg/kg. Mammary gland and behavioral endpoints were also affected by neonatal genistein treatment. Further, transgenerational effects were observed; female offspring obtained from breeding genistein treated females (25 mg/kg) to control males had increased MOFs. Thus, neonatal treatment with genistein at environmentally relevant doses caused adverse consequences on female development which is manifested in adulthood. Whether adverse effects occur in human infants exposed to soy-based products such as soy infant formulas is unknown but the neonatal murine model may help address some of the current uncertainties since we have shown that many effects obtained from feeding genistin, the glycosolated form of genistein found in soy formula, are similar to those obtained from injecting genistein.

Topics: Animals; Animals, Newborn; Diet; Estrous Cycle; Female; Genistein; Humans; Infant, Newborn; Male; Mammary Glands, Animal; Maternal Behavior; Ovary; Phytoestrogens; Reproduction; Uterine Neoplasms

Chemicals known to disrupt the endocrine system of animal models are assessed for their potential impact on the health of menopausal and postmenopausal women. These "endocrine disrupters" consist of two groups of compounds - man-made and naturally occurring. There is some evidence to suggest that the naturally occurring phytoestrogens, derived from plant material, may have some beneficial effects on menopausal symptoms and the risk of breast cancer, cardiovascular disease and osteoporosis. Further studies are required to confirm these possibilities. Some man-made environmental pollutants appear to increase the risk of breast cancer, although again the evidence is inconclusive. Mechanistic experiments indicate that these chemicals interact with oestrogen receptors and alter metabolism in a number of different ways, some of which may be important in postmenopausal women. Further investigation of the differences in mode of action between the man-made and the natural endocrine disrupters may lead to important insights into their effects on women's health.

Topics: Aged; Animals; Breast Neoplasms; Coronary Disease; Endocrine System; Environmental Pollutants; Female; Humans; Menopause; Middle Aged; Neoplasms, Hormone-Dependent; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Risk Assessment; Uterine Neoplasms; Women's Health

Topics: Diet; Estrogen Replacement Therapy; Estrogens; Female; Humans; Obesity; Ovarian Neoplasms; Papillomaviridae; Papillomavirus Infections; Phytoestrogens; Risk Factors; Smoking; Uterine Cervical Neoplasms; Uterine Neoplasms

Estrogens are known for their proliferative effects on estrogen-sensitive tissues resulting in tumorigenesis. Results of experiments in multiple laboratories over the last 20 years have shown that a large part of the cancer-inducing effect of estrogen involves the formation of agonistic metabolites of estrogen, especially 16-alpha-hydroxyestrone. Other metabolites, such as 2-hydroxyestrone and 2-hydroxyestradiol, offer protection against the estrogen-agonist effects of 16-alpha-hydroxyestrone. An ELISA method for measuring 2- and 16-alpha-hydroxylated estrogen (OHE) metabolites in urine is available and the ratio of urinary 2-OHE/16-alpha-OHE (2/16-alpha ratio) is a useful biomarker for estrogen-related cancer risk. The CYP1A1 enzyme that catalyzes 2-hydroxyestrone (2-OHE1) formation is inducible by dietary modification and supplementation with the active components of cruciferous vegetables, indole-3-carbinol (I-3-C), or diindolylmethane (DIM). Other dietary components, especially omega-3 polyunsaturated fatty acids and lignans in foods like flax seed, also exert favorable effects on estrogen metabolism. Thus, there appear to be effective dietary means for reducing cancer risk by improving estrogen metabolism. This review presents the accumulated evidence to help clinicians evaluate the merit of using tests that measure estrogen metabolites and using interventions to modify estrogen metabolism.

Topics: Breast Neoplasms; Estradiol; Estrogens; Estrogens, Non-Steroidal; Female; Humans; Hydroxylation; Isoflavones; Neoplasms; Phytoestrogens; Plant Preparations; Postmenopause; Uterine Neoplasms; Vegetables

The steroid hormone estrogen influences female and male reproductive system, 17-beta-oestradiol is the major human oestrogen. Phytoestrogens are naturally occurring oestrogens in many foods of plant origin. They are structurally and functionally similar to 17-beta-oestradiol or produce estrogenic effects. It is suggested that phytoestrogens could lower risk of diseases accompanied woman in meno- and postmenopausal stage. They are consider to decrease risk of breast, endometrial and ovarian cancer, osteoporosis, cardiovascular disease. This report presents the literature review on nutritious and health aspects connected with phytoestrogens. Generally authors confirm the possibility of beneficial health effects of phytoestrogens in humans.

Topics: Age Factors; Breast Neoplasms; Cardiovascular Diseases; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Male; Osteoporosis; Ovarian Neoplasms; Phytoestrogens; Plant Preparations; Plants, Edible; Time Factors; Uterine Neoplasms

Uterine fibroids are highly prevalent, benign tumors. They are the leading indication for hysterectomy, and Black women are disproportionally burdened. Soy-based infant formula contains phytoestrogens, and exposure during sensitive developmental windows may adversely affect the developing uterus; early phytoestrogen treatment in rodent studies led to detrimental uterine effects, including increased fibroid risk in Eker rats. Limited epidemiological studies also have suggested increased fibroid development with soy formula infant feeding.. The goal of this study was to examine the association between soy formula feeding in infancy and fibroid development in adulthood.. We evaluated this association among 1,610 Black/African-American women age 23-35 y in the Study of Environment, Lifestyle & Fibroids (SELF). Soy formula feeding data was gathered directly from the participants' mothers (89%). A standardized ultrasound examination was conducted during 4 clinic visits over 5 y to detect fibroids. Of 1,121 fibroid-free participants at baseline, 150 (13%) were ever fed soy formula as infants, and 269 (24%) developed incident fibroids. We did not observe an association between ever being fed soy formula and incident fibroid risk (. Adding support to limited human data, this prospective fibroid study found that soy-based formula feeding during infancy was associated with a suggestive increase in risk of ultrasound-identified incident fibroids in adulthood. https://doi.org/10.1289/EHP11089.

Topics: Adult; Animals; Black or African American; Female; Humans; Infant; Infant Formula; Leiomyoma; Phytoestrogens; Prospective Studies; Rats; Uterine Neoplasms; Uterus; Young Adult

Hereinwe investigated the effect of elderflower extracts (EFE) and of enterolactone/enterodiol on hormone production and proliferation of trophoblast tumor cell lines JEG-3 and BeWo, as well as MCF7 breast cancer cells. The EFE was analyzed by mass spectrometry. Cells were incubated with various concentrations of EFE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the EFE on ER/ER/PR expression was assessed by immunocytochemistry. EFE contains a substantial amount of lignans. Estradiol production was inhibited in all cells in a concentration-dependent manner. EFE upregulated ER in JEG-3 cell lines. In MCF7 cells, a significant ER downregulation and PR upregulation were observed. The control substances enterolactone and enterodiol in contrast inhibited the expression of both ER and of PR in MCF7 cells. In addition, the production of estradiol was upregulated in BeWo and MCF7 cells in a concentration dependent manner. The downregulating effect of EFE on ER expression and the upregulation of the PR expression in MFC-7 cells are promising results. Therefore, additional unknown substances might be responsible for ER downregulation and PR upregulation. These findings suggest potential use of EFE in breast cancer prevention and/or treatment and warrant further investigation.

Topics: 4-Butyrolactone; Cell Line, Tumor; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Estradiol; Female; Humans; Immunohistochemistry; Lignans; MCF-7 Cells; Phytoestrogens; Plant Extracts; Pregnancy; Progesterone; Receptors, Estrogen; Sambucus; Trophoblastic Neoplasms; Uterine Neoplasms

Isoflavones and lignans are phytoestrogens, and therefore, are able to bind to and activate estrogen receptors. The resultant estrogenic or antiestrogenic effect is dependent on the concentration of these phytoestrogens relative to endogenous estrogens and the site of their action, among others. Thus, isoflavones and lignans act as selective estrogen receptor modulators; having a beneficial effect in some tissues while simultaneously causing deleterious changes in others.. This case-control study investigates the relationship between urinary concentrations of genistein, daidzein, equol, and enterolactone, and the presence of uterine leiomyomas (fibroids) in Jamaican women.. Phytoestrogen concentration in spot urine samples from 157 uterine fibroid cases and 171 fibroid-free controls diagnosed by ultrasonography, were assessed by Time-resolved Fluoroimmnoassay. Statistical evaluations were performed using SPSS 12.0.. The median concentration of urinary enterolactone was significantly different between uterine fibroid cases and controls (p=0.029). However, this was not observed to affect risk of uterine fibroid, as trends across quartiles of urine enterolactone did not differ significantly between cases and controls. Median urinary genistein (p=0.510), daidzein (p=0.838), equol (p=0.621), total isoflavones (0.510) and total phytoestrogens (p=0.084) were similar for both groups. Binary logistic regression analysis of quartiles of urine genistein, daidzein, equol, enterolactone, total isoflavones, and total phytoestrogens showed no association with uterine fibroid.. Uterine fibroid cases had a higher median urine concentration of enterolactone compared with controls. However, this was not observed to affect ones risk of fibroid. Neither was urine genistein, daidzein, equol total isoflavones, and total phytoestrogens observed to be associated with risk of uterine fibroid.

Topics: Adult; Case-Control Studies; Female; Humans; Isoflavones; Jamaica; Leiomyoma; Phytoestrogens; Risk Factors; Uterine Neoplasms; Women's Health

AIM AND SETTING: To test the effects of crude extracts from flax (Linum usitatissimum) on progesterone and estradiol and ERα and β/PR production in choriocarcinoma cell lines Jeg 3 and BeWo. Tumor trophoblast cells (Jeg 3 and BeWo) were incubated in the presence of different concentrations of the flax crude extracts. Estradiol and progesterone production was measured. Estrogen receptor α and β as well as progesterone receptor expressions were also assessed.. In Jeg 3 cells, progesterone production was downregulated by flax root and leaves extract, while in BeWo cells only flax root extract did manage to downregulate progesterone production. ERβ expression was significantly downregulated by flax root and flax leaves extract in both cell lines; on the contrary, ERα expression was increased by flax leaves extract in BeWo cells. PR expression was downregulated by flax leaves extract in Jeg 3 and by flax root extract in BeWo cells.. Flax extracts derived from leaves and especially from roots can modify progesterone and possibly estradiol production, while at the same time they seem to alter ERβ expression. Further studies on animal models and adequately designed retrospective epidemiological studies are imperative to clarify this role upon progesterone.

Topics: Cell Line, Tumor; Cell Proliferation; Choriocarcinoma; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Flax; Humans; Phytoestrogens; Plant Extracts; Pregnancy; Progesterone; Receptors, Progesterone; Trophoblasts; Uterine Neoplasms

Uterine leiomyomas are the most common gynecological benign tumor and greatly affect reproductive health and well-being. They are the predominant indication for hysterectomy in premenopausal women. Current epidemiological study reported that soy products intake is inversely associated with diseases leading to hysterectomy. Genistein is a soy-derived phytoestrogen and its inhibitory effect on leiomyoma cell proliferation is reported. In this study, we investigated the siginificant inhibitory effect of genistein on estradiol (E(2))-induced leiomyoma cells proliferation.. The Eker rat-derived uterine leiomyoma cell line ELT-3 cells were used. Cell proliferation was assessed by counting the number of cells. The expression of estrogen receptors and peroxisome proliferator-activated receptor-gamma (PPARgamma) was evaluated by Western blot analysis.. PPARgamma was expressed in ELT-3 cells and genistein acted as PPARgamma ligand. This inhibitory effect of genistein was attenuated by the treatment of cells with PPARgamma antagonist bisphenol A diglycidyl ether (BADGE) or GW9662.. These experimental findings in vitro show that the repressive effect of genistein on E(2)-induced ELT-3 cell proliferation is through the activation of PPARgamma. Genistein may be useful as an alternative therapy for leiomyoma.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Estradiol; Female; Genistein; Leiomyoma; Ligands; Phytoestrogens; PPAR gamma; Rats; Receptors, Estrogen; Uterine Neoplasms

The developing fetus is uniquely sensitive to perturbation with estrogenic chemicals. The carcinogenic effect of prenatal exposure to diethylstilbestrol (DES) is the classic example. Because phytoestrogen use in nutritional and pharmaceutical applications for infants and children is increasing, we investigated the carcinogenic potential of genistein, a naturally occurring plant estrogen in soy, in an experimental animal model previously reported to result in a high incidence of uterine adenocarcinoma after neonatal DES exposure. Outbred female CD-1 mice were treated on days 1-5 with equivalent estrogenic doses of DES (0.001 mg/kg/day) or genistein (50 mg/kg/day). At 18 months, the incidence of uterine adenocarcinoma was 35% for genistein and 31% for DES. These data suggest that genistein is carcinogenic if exposure occurs during critical periods of differentiation. Thus, the use of soy-based infant formulas in the absence of medical necessity and the marketing of soy products designed to appeal to children should be closely examined.

Topics: Adenocarcinoma; Animals; Diethylstilbestrol; Estrogens, Non-Steroidal; Fallopian Tubes; Female; Genistein; Isoflavones; Male; Mice; Phytoestrogens; Plant Preparations; Pregnancy; Uterine Neoplasms; Uterus

Topics: Animals; Animals, Newborn; Carcinogenicity Tests; Diethylstilbestrol; Estrogens, Non-Steroidal; Female; Genistein; Isoflavones; Mice; Mutagens; Organ Size; Phytoestrogens; Plant Preparations; Uterine Neoplasms; Uterus