Blackcurrant extract promotes differentiation of MC3T3­E1 pre­osteoblasts.

Osteoporosis risk increases in menopausal individuals owing to the decrease in estrogen secretion. Blackcurrant extract (BCE) ameliorates osteoporosis; however, the underlying mechanisms are unclear. Furthermore, although BCE has phytoestrogenic activity, its effects on osteoblasts are unknown. In the present study, we investigated BCE-mediated attenuation of osteoporosis using mouse MC3T3-E1 pre-osteoblasts, with a focus on osteogenesis. After treating MC3T3-E1 cells with BCE for 48 h, cell proliferation was assessed using Cell Counting Kit-8. Levels of osteoblast differentiation markers, namely alkaline phosphatase activity and total collagen content in the cells, were evaluated after 3 and 14 days of BCE treatment, respectively. The expression of genes encoding osteoblast differentiation markers, including collagen type I (Col-I), alkaline phosphatase (Alp), bone γ-carboxyglutamate protein (Bglap), and runt-related transcription factor 2 (Runx2), was evaluated using reverse transcription-quantitative polymerase chain reaction. Mineralization of the cells was evaluated using Alizarin Red staining. Femoral tissues of ovariectomized (OVX) rats with or without 3% BCE were stained using ALP to evaluate osteogenic differentiation in femoral tissue. After treating MC3T3-E1 cells with BCE, cell proliferation had increased. BCE treatment increased Alp activity and total collagen content. Moreover, the expression of Col-I, Alp, Bglap, and Runx2 increased in BCE-treated cells. Furthermore, when MC3T3-E1 cells were treated with BCE for 21 days, the levels of calcified nodules increased. Alp staining intensity was stronger in the epiphyses on femoral tissue of OVX rats treated with 3% BCE than in those of untreated OVX rats. The results suggest that BCE may promote osteogenesis by inducing osteoblast differentiation.

Extraction of kaempferol derivatives from Zygophyllum paulayanum and its diverse biological activities.

Zygophyllum paulayanum (Zygophyllaceae), is a plant commonly found in the desert region, well-known for its antioxidant, anticancer, wound healing, anti-inflammatory and antibacterial, properties. In this present work, we have studied the extraction of kaempferol derivatives from Z. paulayanum which showed excellent biological activities. The whole plant (root, leaves and stem) was extracted using ethanol, hydrolysed with HCl, and studied for the identification of active molecules. Different techniques like TLC, HPLC, and LCMS have been used to identify and confirm the kaempferol aglycone flavonoid. A mass spectrometric method based on electrospray ionisation has confirmed the presence of kaempferol flavonoid. Apart from the hydrolysed extract, the unhydrolyzed extract was also tested for LCMS which confirms the presence of glycosides such as kaempferol 3-O-beta-D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside, kaempferol 3-O-ß -rutinoside and kaempferol-3-o-rhamnoside. Both extracts of Z. paulayanum exhibited superior antioxidant, anti-inflammatory, antimicrobial, phytoestrogenic and cytotoxic properties which might be due to the presence of kaempferol derivatives.

Alleviation of Menopausal Symptoms by Yam (Dioscorea japonica Thunb.) and Gromwell (Lithospermum erythrorhizon Sieb. Et Zucc.) Extracts in Ovariectomized Mice.

SCOPE: The decline in estrogen during menopause contributes to a variety of menopausal symptoms, for which hormone replacement therapy (HRT) has been extensively applied. Regarding side effects and limited effectiveness of HRT for specific individuals, there is a growing interest in safe alternatives such as phytoestrogens which are structurally analogous to estrogens. This study aims to investigate the efficacy of yam and gromwell extracts, rich in bioactive compounds, and the synergistic effect of extracts on symptoms induced by estrogen deficiency in ovariectomized (OVX) mice. METHODS AND RESULTS: OVX mice receive dietary intervention of either yam, gromwell extract, or their mixture for 14 weeks. Sham-operated mice and E2-injected OVX mice serve as positive controls. Following 14 weeks of oral administration, blood, adipose tissue, vagina, uterus, femurs, and tibias are harvested for further investigation. Consequently, yam and gromwell extracts ameliorate menopausal conditions such as weight gain, glucose intolerance, dyslipidemia, and osteoporosis in estrogen-deficient OVX mice. In addition, the mixture of yam and gromwell extracts synergistically aids in the relief of the indications. CONCLUSION: These results indicate the potential use of yam and gromwell extracts, as well as their mixture, for the development of healthy functional foods to modulate menopausal symptoms.

Effect of polar fractions of Marsilea crenata C. Presl. leaves in zebrafish locomotor activity.

Neurodegenerative diseases (NDs) are pathological conditions initiated by the loss of neuronal cell structure and the progressive decline in function caused by prolonged neuroinflammation. Postmenopausal women are at a high risk of experiencing NDs due to estrogen deficiency in their bodies, necessitating the administration of phytoestrogens as a replacement for estrogen in the body. One alternative therapy is administering phytoestrogens, estrogen-like substances from plants, which can be obtained from Marsilea crenata C. Presl. leaves. The purpose of this study was to determine whether administration of the n-butanol fraction (BF) and water fraction (WF) of M. crenata leaves could increase locomotor activity in rotenone-induced zebrafish. Treatment was given to each group of zebrafish with BF and WF at doses of 2.5; 5; 10; and 20 ppm to determine the locomotor activity. Then an analysis was carried out by looking at each movement of the zebrafish swimming for 1 min at the time of observation on days 0, 7, 14, 21, and 28. The result showed that BF and WF significantly increased the locomotor activity of zebrafish at the optimum dose of 20 ppm for BF and 5 ppm for WF compared to the negative control. This concludes that the polar fraction of M. crenata leaves is proven to have the potential to prevent ND progressivity.

Estrogenic Isoflavones in Clover Plants, Flower Nectar, Unripe Honeys and Mature Honeys: A Natural Biochemical Transformation of Isoflavones by Honeybees.

This study is the first to report on the presence of oestrogenic compounds in different clover flower nectar samples, in bee-deposited nectars collected from hive combs (unripe honey) and in mature honeys harvested from the same hives. The clover species investigated were two red clover (Trifolium pratense) cultivars, bred specifically for high isoflavone content, alongside a sainfoin (Onobrychis viciifolia) and a purple clover (T. purpureum) cultivar. A total of eight isoflavones, four of them non-glycosidic (biochanin A, formononetin, genistein and daidzein) the others glycosidic (sissotrin, ononin, genistin and daidzin), were targeted for identification and quantification in this study using high-performance thin-layer chromatography (HPTLC). Leaves and flower bracts of the clover samples were also investigated. Different isoflavone profiles were found across the four clover species and also in the different samples collected from each species indicating that, most likely due to the activity of honeybee (Apis mellifera) salivary enzymes, biochemical conversions take place when these bioactive compounds transition from flower nectar into ripe honey. Among the four investigated clover species, the two red clover cultivars, including their honeys, were found to contain higher levels of estrogenic compounds compared to other two cultivars.

Daidzein ameliorates nonmotor symptoms of manganese-induced Parkinsonism in zebrafish model: Behavioural and biochemical approach.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a prevalent neurodegenerative movement disorder characterized by motor dysfunction. Environmental factors, especially manganese (Mn), contribute significantly to PD. Existing therapies are focused on motor coordination, whereas nonmotor features such as neuropsychiatric symptoms are often neglected. Daidzein (DZ), a phytoestrogen, has piqued interest due to its antioxidant, anti-inflammatory, and anxiolytic properties. Therefore, we anticipate that DZ might be an effective drug to alleviate the nonmotor symptoms of Mn-induced Parkinsonism. EXPERIMENTAL APPROACH: Naïve zebrafish were exposed to 2 mM of Mn for 21 days and intervened with DZ. Nonmotor symptoms such as anxiety, social behaviour, and olfactory function were assessed. Acetylcholinesterase (AChE) activity and antioxidant enzyme status were measured from brain tissue through biochemical assays. Dopamine levels and histology were performed to elucidate neuroprotective mechanism of DZ. KEY RESULTS: DZ exhibited anxiolytic effects in a novel environment and also improved intra and inter fish social behaviour. DZ improved the olfactory function and response to amino acid stimuli in Mn-induced Parkinsonism. DZ reduced brain oxidative stress and AChE activity and prevented neuronal damage. DZ increased DA level in the brain, collectively contributing to neuroprotection. CONCLUSION AND IMPLICATIONS: DZ demonstrated a promising effect on alleviating nonmotor symptoms such as anxiety and olfactory dysfunction, through the mitigation of cellular damage. These findings underscore the therapeutic potential of DZ in addressing nonmotor neurotoxicity induced by heavy metals, particularly in the context of Mn-induced Parkinsonism.

Sex-specific pharmacokinetic response to phytoestrogens in Drosophila melanogaster.

Drosophila melanogaster, or the fruit fly, is widely used for modeling numerous human diseases, such as neurodegeneration, tumor development, cachexia, and intestinal dysfunction. It is a suitable model organism for research targeting the physiology and pathophysiology of the intestinal epithelial barrier and has also been used as a model organism for preliminary drug and bioactive nutrient screening. However, the application of D. melanogaster in research on drug bioavailability and pharmacokinetic properties has not yet been well explored. In this study, we applied D. melanogaster to investigate the absorption and excretion of the orally administered phytoestrogens daidzein, glycitein, genistein, and their glycosides. Therefore, we established a quick, noninvasive method to quantify compound retention in D. melanogaster, suitable for the investigation of a broad variety of potentially bioactive substances. We showed that fruit fly sex plays a key role in the metabolization, transportation, and excretion of phytoestrogenic isoflavones. In particular, female fruit flies retained significantly more isoflavones than male fruit flies, which was reflected in the greater metabolic impact of isoflavones on females. Male fruit flies excreted more isoflavones than females did, which was linked to the upregulation of the xenobiotic transporter gene Mdr50. We also demonstrated that micellized isoflavones were more bioavailable than powdered isoflavones, independent of sex, age or the addition of dietary fibers.

A Case Study Based on the Effect of Phytoestrogen on an Oligozoospermic Patient.

We presented a 30-year-old man suffering from severe oligozoospermia caused by substantial sperm maturation arrest around the spermatid stage. Additionally, he was suffering from a varicocele. For three years, the couple had been trying to conceive. The clinical and endocrinological evaluation of the woman revealed that she was medically fit to undergo pregnancy. We performed laparoscopic ligation of the spermatic vein to treat the varicocele. Semen analysis was conducted at the beginning of the clinical pregnancy journey and after three and six months of treatment, which included 80 mg/day of phytoestrogens for six months. Six months following the end of the therapy, a second semen analysis was carried out. The inherent characteristics of the semen substantially improved in the third month, facilitating the implementation of the reproductive method referred to as intrauterine insemination. Following this treatment, the patient delivered a healthy baby weighing 3300 g. Sperm parameters improved substantially after three months of therapy; however, they reverted to baseline values during the wash-out period. These promising findings strongly suggest that phytoestrogens could be utilized for therapeutic purposes in the management of oligozoospermia. To further demonstrate the potential impact of phytoestrogens on male infertility, it is imperative to conduct a validation phase and randomized controlled trials.

Tissue distribution and pharmacokinetics of isoxanthohumol from hops in rodents.

Vegetables and fruits contain prenylflavonoids with biological functions that might improve human health. The prenylflavonoid isoxanthohumol (IXA) and its derivative, 8-prenylnaringenin (8-PN), have beneficial activities, including anti-cancer effects and suppression of insulin resistance. However, their pharmacokinetic profile is unclear. Previous studies suggested flavonoids have low systemic availability and are excreted via the feces. Therefore, this study investigated the tissue distribution dynamics of high-purity IXA (>90%) from hops administered orally, either singly (50 mg/kg body weight [BW]) or daily for 14 days (30 mg/kg BW), to mice. High-pressure liquid chromatography demonstrated that IXA was absorbed rapidly after a single administration and reached plasma maximum concentration (C max) (3.95 ± 0.81 µmol/L) by 0.5 h. IXA was present at high levels in the liver compared with the kidney, pancreas, lung, skeletal muscle, spleen, thymus, and heart. The highest IXA level after 14 days of IXA ingestion was observed in the liver, followed by the kidney, thymus, spleen, lung, and brain. There was no significant difference in IXA accumulation in tissues between the single and multiple dose groups. Analyses of the livers of rats treated with different concentrations of IXA (112.5-1500 mg/kg BW) once a day for 28 days demonstrated that IXA accumulated dose-dependently with a correlation coefficient of .813. The accumulation of 8-PN was dependent on the intake period but not the intake amount of IXA (correlation coefficient -.255). In summary, IXA and 8-PN were detected in tissues and organs up to 24 h after ingestion, suggesting that orally ingested IXA might have health benefits as a nutraceutical.

Giant endometrial polyp in a post-menopausal woman: a rare case report from Nepal.

Introduction: Endometrial polyps (EPs) result from the overgrowth of endometrial glands and stroma. Giant endometrial polyps, defined as those exceeding 4 cm, are rare, and their association with phytoestrogen (PE) intake is infrequently reported. Case presentation: The authors present a case of a giant endometrial polyp in a 59-year-old post-menopausal woman from Nepal. The patient presented with lower abdominal pain and a history of vaginal spotting. She was not under any drugs or medications, including hormones, but had a regular intake of PE-rich foods. Imaging revealed a giant endometrial polyp and a uterine fibroid. Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) were performed and histopathology examination confirmed the diagnosis of endometrial polyp and fibroid. Discussion: In our case, the patient's increased age and PE-rich diet were identified as potential risk factors for the giant endometrial polyp. Giant endometrial polyps are rare, with limited cases reported to date, often associated with tamoxifen or raloxifene use. Phytoestrogens can exhibit oestrogenic effects, contributing to endometrial polyps. This case emphasizes the importance of further research to explain the relationship between phytoestrogen intake and giant endometrial polyps. Conclusion: Giant endometrial polyps are uncommon, and their association with phytoestrogen intake remains underexplored. Clinicians should consider dietary factors in history while evaluating endometrial polyps, and further research is necessary to explore the potential role of phytoestrogens in the development of giant endometrial polyps.

Oestrogens, adipose tissues and environmental exposures influence obesity and diabetes across the lifecycle.

Endogenous oestrogens regulate essential functions to include menstrual cycles, energy balance, adipose tissue distribution, pancreatic ß-cell function, insulin sensitivity and lipid homeostasis. Oestrogens are a family of hormones which include oestradiol (E2), oestrone (E1) and oestriol (E3). Oestrogens function by binding and activating oestrogen receptors (ERs). Phytoestrogens are plant-derived compounds which exhibit oestrogenic-like activity and can bind to ERs. Phytoestrogens exert potential oestrogenic-like benefits; however, their effects are context-dependent and require cautious consideration regarding generalised health benefits. Xenoestrogens are synthetic compounds which have been determined to disrupt endocrine function through binding to ERs. Xenoestrogens enter the body through various routes and given their chemical structure they can accumulate, posing long-term health risks. Xenoestrogens interfere with endogenous oestrogens and their functions contributing to conditions like cancer, infertility, and metabolic disorders. Understanding the interplay between endogenous and exogenous oestrogens is critical in order to determine their potential health consequences and requires further investigation. This manuscript provides a summary of the role endogenous oestrogens have in regulating metabolic functions. Additionally, we discuss the impact phytoestrogens and synthetic xenoestrogens have on biological systems across various life stages. We highlight their mechanisms of action, potential benefits, risks and discuss the need for further research to bridge gaps in understanding and mitigate exposure-related health risks.

From Gut to Hormones: Unraveling the Role of Gut Microbiota in (Phyto)Estrogen Modulation in Health and Disease.

The human gut microbiota regulates estrogen metabolism through the "estrobolome," the collection of bacterial genes that encode enzymes like ß-glucuronidases and ß-glucosidases. These enzymes deconjugate and reactivate estrogen, influencing circulating levels. The estrobolome mediates the enterohepatic circulation and bioavailability of estrogen. Alterations in gut microbiota composition and estrobolome function have been associated with estrogen-related diseases like breast cancer, enometrial cancer, and polycystic ovarian syndrome (PCOS). This is likely due to dysregulated estrogen signaling partly contributed by the microbial impacts on estrogen metabolism. Dietary phytoestrogens also undergo bacterial metabolism into active metabolites like equol, which binds estrogen receptors and exhibits higher estrogenic potency than its precursor daidzein. However, the ability to produce equol varies across populations, depending on the presence of specific gut microbes. Characterizing the estrobolome and equol-producing genes across populations can provide microbiome-based biomarkers. Further research is needed to investigate specific components of the estrobolome, phytoestrogen-microbiota interactions, and mechanisms linking dysbiosis to estrogen-related pathology. However, current evidence suggests that the gut microbiota is an integral regulator of estrogen status with clinical relevance to women's health and hormonal disorders.

Causes of Low Milk Supply: The Roles of Estrogens, Progesterone, and Related External Factors.

Low milk supply (LMS) poses a significant challenge to exclusive and continued breastfeeding, affecting ∼10% to 15% of mothers. Milk production is intricately regulated by both endocrine and autocrine control mechanisms, with estrogens and progesterone playing pivotal roles in this process. In addition to endogenously produced hormones, external substances capable of interfering with normal hormonal actions, including phytoestrogens, mycoestrogens, synthetic estrogens, and hormonal contraceptives, can influence milk production. The effects of these extrinsic hormones on milk production may vary based on maternal body mass index. This comprehensive review examines the multifaceted causes of LMS, focusing on the involvement of estrogens, progesterone, and related external factors in milk production. Furthermore, it investigates the interplay between hormonal factors and obesity, aiming to elucidate the endocrine mechanisms underlying obesity-associated LMS. Insights from this review provide valuable perspectives for developing interventions to improve milk production and address the challenges associated with LMS.

Polyphenols as potential preventers of osteoporosis: A comprehensive review on antioxidant and anti-inflammatory effects, molecular mechanisms, and signal pathways in bone metabolism.

Osteoporosis (OP) is a skeletal disorder characterized by decreased bone density, alterations in bone microstructure, and increased damage to the bones. As the population ages and life expectancy increases, OP has become a global epidemic, drawing attention from scientists and doctors. Because of polyphenols have favorable antioxidant and anti-allergy effects, which are regarded as potential methods to prevent angiocardipathy and OP. Polyphenols offer a promising approach to preventing and treating OP by affecting bone metabolism, reducing bone resolution, maintaining bone density, and lowering the differentiation level of osteoclasts (OC). There are multiple ways in which polyphenols affect bone metabolism. This article provides an overview of how polyphenols inhibit oxidative stress, exert antibacterial effects, and prevent the occurrence of OP. Furthermore, we will explore the regulatory mechanisms and signaling pathways implicated in this process.

From Plants to Therapies: Exploring the Pharmacology of Coumestrol for Neurological Conditions.

Neurological disorders are possibly the most prevalent and have been identified to occur among individuals with autism beyond chance. These disorders encompass a diverse range of consequences with neurological causes and have been regarded as a major threat to public mental health. There is no tried-and-true approach for completely protecting the nervous system. Therefore, plant-derived compounds have developed significantly nowadays. Coumestrol (CML) is a potent isoflavone phytoestrogen with a protective effect against neurological dysfunction and has been discovered to be structurally and functionally similar to estrogen. In recent years, more research has been undertaken on phytoestrogens. This research demonstrates the biological complexity of phytoestrogens, which consist of multiple chemical families and function in various ways. This review aimed to explore recent findings on the most significant pharmacological advantages of CML by emphasising neurological benefits. Numerous CML extraction strategies and their pharmacological effects on various neurological disorders, including PD, AD, HD, anxiety, and cognitive impairments, were also documented.

Anti-Influenza Virus Activity of Citrullus lanatus var. citroides as a Functional Food: A Review.

Influenza is an acute respiratory illness caused by the influenza virus, in response to which vaccines and antiviral drugs are administered. In recent years, the antiviral effects of plants and foods have garnered attention. This review is the first to summarize the therapeutic properties of wild watermelon (Citrullus lanatus var. citroides) against influenza from a phytochemical viewpoint. Wild watermelon is a wild plant with significant potential as a therapeutic candidate in antiviral strategies, when focused on its multiple anti-influenza functionalities. Wild watermelon juice inhibits viral growth, entry, and replication. Hence, we highlight the possibility of utilizing wild watermelon for the prevention and treatment of influenza with stronger antiviral activity. Phytochemicals and phytoestrogen (polyphenol, flavonoids, and prenylated compounds) in wild watermelon juice contribute to this activity and inhibit various stages of viral replication, depending on the molecular structure. Wild plants and foods closely related to the original species contain many natural compounds such as phytochemicals, and exhibit various viral growth inhibitory effects. These natural products provide useful information for future antiviral strategies.

Diet-microbiome-immune interplay in multiple sclerosis: Understanding the impact of phytoestrogen metabolizing gut bacteria.

Multiple sclerosis (MS) is a chronic and progressive autoimmune disease of the central nervous system (CNS), with both genetic and environmental factors contributing to the pathobiology of the disease. Although HLA genes have emerged as the strongest genetic factor linked to MS, consensus on the environmental risk factors is lacking. Recently, the gut microbiota has garnered increasing attention as a potential environmental factor in MS, as mounting evidence suggests that individuals with MS exhibit microbial dysbiosis (changes in the gut microbiome). Thus, there has been a strong emphasis on understanding the role of the gut microbiome in the pathobiology of MS, specifically, factors regulating the gut microbiota and the mechanism(s) through which gut microbes may contribute to MS. Among all factors, diet has emerged to have the strongest influence on the composition and function of gut microbiota. As MS patients lack gut bacteria capable of metabolizing dietary phytoestrogen, we will specifically discuss the role of a phytoestrogen diet and phytoestrogen metabolizing gut bacteria in the pathobiology of MS. A better understanding of these mechanisms will help to harness the enormous potential of the gut microbiota as potential therapeutics to treat MS and other autoimmune diseases.

Systems biology based miRNA-mRNA expression pattern analysis of Emodin in breast cancer cell lines.

Breast cancer has been among the most prominent cancers with high mortality. Currently most of the offered therapeutics are toxic; hence, less toxic therapeutic intervention is required. Here, we studied the molecular mechanisms of the effect of a phytoestrogen Emodin on estrogen receptor positive MCF-7 and negative MDA-MB-231 cells by carrying out a comprehensive network assessment. Differentially expressed microRNAs along with their previously identified differentially expressed mRNAs were analyzed through microarrays by using integrative systems biology approach. For each cell line miRNA-target gene networks were built, gene ontology and pathway enrichment analyses were performed, enrichment maps were constructed and the potential key genes, miRNAs and miRNA-gene interactions were studied.

Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer.

Nano-targeted delivery systems have been widely used for breast tumor drug delivery. Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells. However, targeted ligands have a significant impact on the safety and effectiveness of active delivery systems, limiting the clinical transformation of nanoparticles. Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor. In the present study, molecular docking was used to select tanshinone IIA (Tan IIA) among phytoestrogens as a target ligand to be used in nanodelivery systems with some modifications. Modified Tan IIA (Tan-NH2) showed a good biosafety profile and demonstrated tumor-targeting, anti-tumor and anti-tumor metastasis effects. Moreover, the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN. Tan-Dox-MSN had a uniform particle size, good dispersibility and high drug loading capacity. Validation experiments in vivo and in vitro showed that it also had a better targeting ability, anti-tumor effect and lower toxicity in normal organs. These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.

Insight into the Potential Mechanisms of Endocrine Disruption by Dietary Phytoestrogens in the Context of the Etiopathogenesis of Endometriosis.

Phytoestrogens (PEs) are estrogen-like nonsteroidal compounds derived from plants (e.g., nuts, seeds, fruits, and vegetables) and fungi that are structurally similar to 17ß-estradiol. PEs bind to all types of estrogen receptors, including ERα and ERß receptors, nuclear receptors, and a membrane-bound estrogen receptor known as the G protein-coupled estrogen receptor (GPER). As endocrine-disrupting chemicals (EDCs) with pro- or antiestrogenic properties, PEs can potentially disrupt the hormonal regulation of homeostasis, resulting in developmental and reproductive abnormalities. However, a lack of PEs in the diet does not result in the development of deficiency symptoms. To properly assess the benefits and risks associated with the use of a PE-rich diet, it is necessary to distinguish between endocrine disruption (endocrine-mediated adverse effects) and nonspecific effects on the endocrine system. Endometriosis is an estrogen-dependent disease of unknown etiopathogenesis, in which tissue similar to the lining of the uterus (the endometrium) grows outside of the uterus with subsequent complications being manifested as a result of local inflammatory reactions. Endometriosis affects 10-15% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. In this review, the endocrine-disruptive actions of PEs are reviewed in the context of endometriosis to determine whether a PE-rich diet has a positive or negative effect on the risk and course of endometriosis.