Synthetic Estrogen Research Articles

Impact of Obesity, Menopause, and Depression in Women's Health: An Attempt to Decipher the Complex Relationship.

Menopause symptoms may be distressing, especially when they appear at a time when women are expected to play significant responsibilities in society. Numerous biological systems are influenced by the hormonal changes that start during the menopausal transition. This review attempts to decipher the complex relationship between obesity, menopause, and depression, citing some recent longitudinal and cross-sectional studies. Additionally, this study provides a summary of the different phytoestrogens, their sources, and probable mechanisms of action in addition to available therapeutic alternatives. For this review purpose, the authors have gone through a vast number of articles from various scientific databases like PubMed, Google Scholar, and Web of Science. It is becoming clear that the physiological basis for these menopausal symptoms is complicated and connected to estrogen deficiency, but not alone. Other hormones like FSH, LH, progesterone, and inhibin B are the major ones that are both directly and indirectly responsible for most of the menopausal symptoms. Numerous longitudinal and cross-sectional studies have found a direct relationship between the incidence of menopause and depression as well as obesity. Phytoestrogens like stilbene, lignans, isoflavone, and coumestan have been reported to be the alternatives to synthetic estrogen with lesser side effects, as reported in various studies. The complex relationship between depression, menopause, and obesity presents a complex obstacle to women's health and overall well-being. There might be a lot of promising prospects for revolutionary advancements in women's health during the menopausal stage in the future. Promising drug development that targets not just one but also the three conditions -obesity, menopause, and depression - as well as more thorough research are needed to improve the healthcare system for women who suffer from these conditions.

Lower reporting of venous thromboembolisms events with natural estrogen-based combined oral contraceptives compared to ethinylestradiol-containing pills: A disproportionality analysis of the Eudravigilance database

ObjectivesPharmacovigilance data analysis can accelerate the identification of drug-related safety signals or reassure on the safety profile. This study evaluates the venous thromboembolism (VTE) risk of newer combined oral contraceptive (COC) formulations with natural estrogens, such as estradiol (E2) and estetrol (E4), using data from the EudraVigilance database. Study designWe conducted a disproportionality reporting rate analysis of VTE events associated with various COC formulations by extracting individual case reports from EudraVigilance database up to July 28, 2024. The study compared the proportionality reporting rate between natural estrogen-based COCs (E2 and E4) and conventional synthetic estrogen-based COCs (ethinylestradiol [EE]), with a comparison to EE-levonorgestrel. ResultsThe analysis revealed that COCs containing natural estrogens exhibited significantly lower proportionality reporting rates for thrombotic events compared to EE-based COCs. Specifically, E4-drospirenone (E4-DRSP) showed the lowest proportionality reporting rate (0.12), similar to progestin-only pills. EE-DRSP had the highest proportionality reporting rate (2.25), suggesting an increased thrombotic risk. ConclusionsThe study supports the safer thrombotic profile of natural estrogen-based COCs, particularly E2 and E4 formulations, over synthetic estrogen-based COCs containing EE. These findings support the hypothesis that E2- and E4-based pills are safer than EE-based pills, aligning with a shift toward safer contraceptive options in clinical practice. ImplicationsNatural estrogens such as E2 and E4 may emerge as safer alternatives to synthetic estrogens like EE, particularly when combined with progestins like DRSP. This multilevel evidence underscores the importance of evidence-based prescribing practices to enhance patient safety and minimize thrombotic risks associated with COC use.

The bioassay tests and mass spectrometry for evaluation of xenoestrogens in tuna fish

Exposure to xenoestrogens through food is a significant concern. These compounds have estrogen-like activity and lead to cell proliferation. In this study, MCF-7 cells were utilized for bioassay tests and evaluation of cell proliferation of extracts prepared from canned tuna fish. First, a pre-screening using the MTT test was done with the solid and liquid parts of the canned tuna fish. It was observed that the proliferation of cells in the solid part of canned tuna cans actually occurs in tuna meat. Therefore, this portion of canned tuna fish was selected for further studies. The binding affinity with ERα and ERβ receptors was determined through RT-qPCR, and the extract was analyzed via mass spectrometry to identify estrogenic components. The study revealed an increased cell proliferation rate upon treatment with the canned tuna fish extract. 17β-estradiol was considered as positive control. The cell proliferation rate ranged from 27 % to 36.6 % compared to 17β-estradiol. Both ERα and ERβ receptors of MCF-7 cells were stimulated almost equally in the sample extract group. Mass spectrometry analysis identified bisphenol A(BPA) and other estrogenic compounds such as phytoestrogens, phthalates, polychlorinated biphenyls, natural and synthetic estrogen hormones. Our findings emphasize the necessity of using a combination of bioassay tests and analytical methods to carefully manage and evaluate the combined estrogenic effects of components in food samples.

Evidence-based neuroprotective potential of nonfeminizing estrogens: In vitro and in vivo studies.

Menopause weakens the brain's structural integrity and increases its susceptibility to a range of degenerative and mental illnesses. 17β estradiol (17βE2) exhibits potent neuroprotective properties. Exogenous estrogen supplementation provides neuroprotection, but the findings presented by the Million Women Study (MWS) and the Women's Health Initiative (WHI), as well as the increased risk of endometrial cancer, breast cancer and venous thromboembolism associated with estrogen use, have cast doubt on its clinical use for neurological disorders. Thus, the objective of our review article is to compile all in vitro and in vivo studies conducted till date demonstrating the neuroprotective potential of nonfeminizing estrogens. This objective has been achieved by gathering various research and review manuscripts from different records such as PubMed, Embase, Scopus, Google Scholar, Web of Science and OVID, using different terms like 'estrogen deficiency, 17β estradiol, non-feminising estrogens, and brain disorder'. However, recent evidence has revealed the contribution of numerous non-estrogen receptor-dependent pathways in neuroprotective effects of estrogen. In conclusion, synthetic nonfeminizing estrogens that have little or no ER binding but are equally powerful (and in some cases more potent) in delivering neuroprotection are emerging as viable and potential alternatives.

A Global Inventory of Natural and Synthetic Estrogens in Aquatic Systems.

Estrogens are a group of endocrine disruptors that are recognized as a threat to the world's ecosystems and are easily transported through aquatic systems from mainly anthropogenic sources. To illustrate this growing problem, we have compiled a global overview of measured concentrations of natural and synthetic estrogens restricted to freshwater systems (lakes, rivers, and lagoons) and marine coastal and open ocean environments, focusing on estrone (E1), 17$\upbeta$-estradiol (E2), estriol (E3), and 17$\upalpha$-ethinylestradiol (EE2). We found that the cumulative risk quotient is high at 65% of 400 sampled sites, highlighting that estrogen pollution is a major environmental concern. Our investigation revealed that almost no information is available on the concentration levels of E1, E2, E3, and EE2 for the open ocean areas. However, their occurrence in all systems, including open seas, suggests that estrogens are not completely degraded during transport to and within the environment and may be more persistent than previously thought.

Spatiotemporal variations and risk assessment of estrogens in the water of the southern Bohai Sea: A comprehensive investigation spanning three years

The ubiquitous and adverse effects of estrogens have aroused global concerns. Natural and synthetic estrogens in 255 water samples from the southern Bohai Sea were analyzed over three years. Total estrogen concentrations were 11.0–268 ng/L in river water and 1.98–99.7 ng/L in seawater, with bisphenol A (BPA) and 17α-ethynylestradiol (EE2) being the predominant estrogens, respectively. Estrogen showed the highest concentrations in summer 2018, followed by spring 2021 and spring 2019, which was consistent with the higher estrogen flux from rivers during summer. Higher estrogen concentrations in 2021 than in 2019 were driven by the higher level of BPA, an additive used in personal protective equipment. Estrogen exhibited higher concentrations in the southern coast of the Yellow River Delta and the northeastern coast of Laizhou bay due to the riverine input and aquaculture. Estrogens could disturb the normal endocrine activities of organisms and edict high ecological risks (90th simulated RQT > 1.0) to aquatic organisms, especially to fish. EE2 was the main contributor of estrogenic potency and ecological risk, which requires special concern. This is the first comprehensive study of estrogen spatiotemporal variations and risks in the Bohai Sea, providing insights into the environmental behavior of estrogens in coastal regions.

Changes in CpG Methylation of the Vitellogenin 1 Promoter in Adult Male Zebrafish after Exposure to 17α-Ethynylestradiol.

Numerous pharmaceutical and industrial chemicals are classified as endocrine-disrupting chemicals (EDCs) that interfere with hormonal homeostasis, leading to developmental disorders and other pathologies. The synthetic estrogen 17α-ethynylestradiol (EE2) is used in oral contraceptives and other hormone therapies. EE2 and other estrogens are inadvertently introduced into aquatic environments through municipal wastewater and agricultural effluents. Exposure of male fish to estrogens increases expression of the egg yolk precursor protein vitellogenin (Vtg), which is used as a molecular marker of exposure to estrogenic EDCs. The mechanisms behind Vtg induction are not fully known, and we hypothesized that it is regulated via DNA methylation. Adult zebrafish were exposed to either dimethyl sulfoxide or 20 ng/L EE2 for 14 days. Messenger RNA (mRNA) expression and DNA methylation were assessed in male zebrafish livers at 0, 0.25, 0.5, 1, 4, 7, and 14 days of exposure; and those of females were assessed at 13 days (n ≥ 4/group/time point). To test the persistence of any changes, we included a recovery group that received EE2 for 7 days and did not receive any for the following 7 days, in the total 14-day study. Methylation of DNA at the vtg1 promoter was assessed with targeted gene bisulfite sequencing in livers of adult male and female zebrafish. A significant increase in vtg1 mRNA was observed in the EE2-exposed male fish as early as 6 h. Interestingly, DNA methylation changes were observed at 4 days. Decreases in the overall methylation of the vtg1 promoter in exposed males resulted in levels comparable to those in female controls, suggesting feminization. Importantly, DNA methylation levels in males remained significantly impacted after 7 days post-EE2 removal, unlike mRNA levels. These data identify an epigenetic mark of feminization that may serve as an indicator of not only estrogenic exposure but also previous exposure to EE2. Environ Toxicol Chem 2024;43:1547-1556. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Patterns of oral contraceptives consumption and estimated concentrations of 17α-ethinylestradiol in water bodies from the municipality of Santa Maria Madalena, Southeastern Brazil

Organic contaminants with estrogenic activity have generated increasing concerns in the scientific community since they are capable of triggering adverse effects in the endocrine system of several organisms. 17α-ethinylestradiol (EE2), a synthetic estrogen used in oral contraceptives, has been identified as one of the main responsible for causing such changes. Thereby the objective of this study was to generate information on EE2 consumption and estimate its possible impact on the water bodies of Santa Maria Madalena. Firstly, a survey was carried out about EE2 consumption through interviews with 325 women aged 15 to 59 residing in the study area, and then estimated the EE2 release in the water bodies. About 30% of the women interviewed reported using oral contraceptives. The EE2 average daily intake for each woman was 20 μg day-1. Extrapolating this intake to 30% of the population and adopting an excretion rate of 57%, it was calculated a total discharge of 4.8 mg day-1 of this estrogen into the local water bodies. It diluted by the small flow of these streams leads to an estimated environmental concentration of 0.3 ng L-1, which according to ecotoxicological studies is already enough to trigger adverse effects to the aquatic biota.

17α-ethinyl estradiol induces behavioral and reproductive damages in zebrafish (Danio rerio)

Synthetic estrogen 17α-ethinyl estradiol (EE2) is recognized for its ability to cause endocrine disruption in aquatic organisms and its high resistance to environmental degradation, being found in Brazilian waterbodies up to 100 ng L-1. Thus, the aim of this study was to evaluate the exploratory behavior and the histological effects on zebrafish gonads, caused by environmentally relevant concentrations of EE2. Females were exposed to nominal concentrations of 25 ng L-1 and 100 ng L-1 EE2 for 21 days. After that, a behavioral and histological analysis of gonads was performed. The EE2 caused the reduction of the exploratory activity of the animals, when observed the behavior, and an acceleration of the maturation process of the oocytes evaluated in the histological analysis. Considering the results obtained after the exposure to EE2, we highlight the concern about the potential risks it may cause to the aquatic biota, alerting to the need to control and monitor these micropollutants present in Brazilian water resources.

Estetrol/drospirenone versus 17α-ethinylestradiol/drospirenone: An extended one generation test to evaluate the endocrine disruption potential on zebrafish (Danio rerio)

Combined oral contraceptives, comprising of both an oestrogen and a progestin component, are released in aquatic environments and potentially pose a risk to aquatic wildlife by their capacity to disrupt physiological mechanisms.In this study, the endocrine disruptive potential of two mixtures, 17α-ethinylestradiol (EE2), a synthetic oestrogen, or estetrol (E4), a natural oestrogen, with the progestin drospirenone (DRSP) have been characterised in three generations of zebrafish, according to an adapted Medaka Extended One Generation Reproduction Test. Zebrafish (Danio rerio) were exposed to a range of concentrations of EE2/DRSP and E4/DRSP (∼1×, ∼3×, ∼10× and ∼30× predicted environmental concentration, PEC). Survival, growth, hatching success, fecundity, fertilisation success, vitellogenin (VTG), gonad histopathology, sex differentiation, and transcriptional analysis of genes related to gonadal sex steroid hormones synthesis were assessed.In the F0 generation, exposure to EE2/DRSP at ∼10 and ∼30× PEC decreased fecundity and increased male VTG concentrations. The highest concentration of EE2/DRSP also affected VTG concentrations in female zebrafish and the expression of genes implicated in steroid hormones synthesis. In the F1 generation, sex determination was impaired in fish exposed to EE2/DRSP at concentrations as low as ∼3× PEC. Decreased fecundity and fertility, and abnormal gonadal histopathology were also observed. No effects were observed in the F2 generation. In contrast, E4/DRSP induced only minor histopathological changes and an increase in the proportion of males, at the highest concentration tested (∼30× PEC) in the F1 generation and had no effect on hatching success of F2 generation.Overall, this study suggests that the combination E4/DRSP has a more favourable environmental profile than EE2/DRSP.

Estradiol-17β and bisphenol A affect growth and mineralization in early life stages of seabass

Natural and synthetic estrogens are contaminants present in aquatic ecosystems. They can have significant consequences on the estrogen-sensitive functions of organisms, including skeletal development and growth of vertebrate larvae. Synthetic polyphenols represent a group of environmental xenoestrogens capable of binding the receptors for the natural hormone estradiol-17β (E2). To better understand how (xeno-)estrogens can affect the skeleton in fish species with high ecological and commercial interest, 16 days post-hatch larvae of the seabass were experimentally exposed for 7 days to E2 and Bisphenol A (BPA), both used at the regulatory concentration of surface water quality (E2: 0.4 ng.L−1, BPA: 1.6 μg.L−1) or at a concentration 100 times higher. Skeletal mineralization levels were evaluated using Alizarin red staining, and expression of several genes playing key roles in growth, skeletogenesis and estrogen signaling pathways was assessed by qPCR. Our results show that E2 exerts an overall negative effect on skeletal mineralization at the environmental concentration of 0.4 ng.L−1, correlated with an increase in the expression of genes associated only with osteoblast bone cells. Both BPA exposures inhibited mineralization with less severe effects and modified bone homeostasis by regulating the expression of gene encoding osteoblasts and osteoclasts markers. Our results demonstrate that environmental E2 exposure inhibits larval growth and has an additional inhibitory effect on skeleton mineralization while both BPA exposures have marginal inhibitory effect on skeletal mineralization. All exposures have significant effects on transcriptional levels of genes involved in the skeletal development of seabass larvae.

Comparison of in vitro Toxicities of 8-Prenylnaringenin, Tartrazine and 17β-Estradiol, Representatives of Natural and Synthetic Estrogens, in Rat and Human Hepatoma Cell Lines

ABSTRACT Background: Phytoestrogens have been praised for their beneficial health effects, whereas synthetic xenoestrogens have been connected to ailments. Aims: To ascertain whether the toxicities of natural and synthetic estrogens differ, we examined the potent phytoestrogen 8-prenylnaringenin (8-PN), the common synthetic xenoestrogen tartrazine, and the physiological estrogen 17β-estradiol (E2). Methods: These three compounds were tested for cytotoxicity, cell proliferation and genotoxicity in human HepG2 and rat H4IIE hepatoma cells. Results: All three estrogens elicited cytotoxicity at high concentrations in both cell lines. They also inhibited cell proliferation, with E2 being the most effective. They all tended to increase micronuclei formation. Conclusion: Natural estrogens were no less toxic than a synthetic one.

Sensitivity of cholinesterases and carboxylesterases to pharmaceutical products in Tinca tinca.

Discharges to the aquatic environment of pharmaceuticals represent a hazard to the aquatic organisms. Subchronic assay with 17-alpha-ethinylestradiol (EE2) and in vitro essays with pharmaceuticals of environmental concern were conducted to examine the sensitivity of tissue acetylcholinesterase (AChE) and carboxylesterase (CbE) activities of Tinca tinca to them. Subchronic exposure to 17-alpha-EE2 caused significant effects on brain, liver, and muscle CbE, but no on AChE activities. Most of the pharmaceuticals tested in vitro were considered as weak inhibitors of tissular AChE activity. Depending on the tissues, some compounds were classified as moderate inhibitors of CbE activity while other were categorized as weak enzymatic inhibitors. An opposite trend was observed depending on the tissue, while brain and liver CbE activities were inhibited, the muscle CbE activity was induced. Changes experienced on enzymatic activities after exposure to pharmaceuticals might affect the physiological functions in which these enzymes are involved. In vitro exposure to 17-alpha-EE2 in tench could be an informative, but not a surrogate model to know the effect of this synthetic estrogen on AChE and CbE activities.

Use of All-Male cyp17a1-Deficient Zebrafish (Danio rerio) for Evaluation of Environmental Estrogens.

Natural and synthetic environmental estrogens (EEs) are widespread and have received extensive attention. Our previous studies demonstrated that depletion of the cytochrome P450 17a1 gene (cyp17a1) leads to all-testis differentiation phenotype in zebrafish and common carp. In the present study, cyp17a1-deficient zebrafish with defective estrogen biosynthesis were used for the evaluation of EEs, as assessed by monitoring vitellogenin (vtg) expression. A rapid and sensitive assessment procedure was established with the 3-day administration of estradiol (E2), followed by examination of the transcriptional expression of vtgs in our cyp17a1-deficient fish. Compared with the control fish, a higher E2-mediated vtg upregulation observed in cyp17a1-deficient zebrafish exposed to 0.1 μg/L E2 is known to be estrogen receptor-dependent and likely due to impaired in vivo estrogen biosynthesis. The more responsive vtg expression in cyp17a1-deficient zebrafish was observed when exposed to 200 and 2000 μg/L bisphenol A (BPA) and perfluoro-1-octanesulfonate (PFOS). The estrogenic potentials of E2, BPA, and PFOS were compared and assessed by the feminization effect on ovarian differentiation in cyp17a1-deficient zebrafish from 18 to 50 days postfertilization, based on which a higher sensitivity of E2 in ovarian differentiation than BPA and PFOS was concluded. Collectively, through the higher sensitivity to EEs and the capacity to distinguish chemicals with different estrogenic potentials exhibited by the all-male cyp17a1-deficient zebrafish with impaired estrogen biosynthesis, we demonstrated that they can be used as an excellent in vivo model for the evaluation of EEs. Environ Toxicol Chem 2024;43:1062-1074. © 2024 SETAC.

Prolame produces anxiolytic- and antidepressant-like effects in middle-aged female rats with less uterotrophic effects than 17β-estradiol

Estrogen hormone replacement therapy (EHRT), improving women's life quality at menopause, reduces anxiety and depression symptoms associated with ovarian hormonal decline. However, its potential adverse effects, like thromboembolism and cancer risk, limit its use. Prolame is a synthetic 17β-amino estrogen with antithrombotic actions that exerts anxiolytic- and antidepressant-like effects on young adult ovariectomized female rats. It is unknown if prolame's effects may be observed in age and endocrine conditions emulating menopause. This study aimed to identify the antidepressant- and anxiolytic-like effects of prolame and E2 (used as a reference estrogen treatment) in middle-aged female rats coursing with irregular cycles, in two different conditions: ovariectomized or gonadally intact. Results were compared with those from young adult ovariectomized rats. Prolame (60 or 120 μg/kg), 17β-estradiol (E2, 40 or 80 μg/kg), or vehicle were chronically administered, and their effects were evaluated in the elevated plus-maze, defensive burying behavior test, open field test, and forced swimming test. Uterotrophic actions were estimated by uterine weight related to body weight. Prolame and E2 produced robust anxiolytic- and antidepressant-like effects in young adult ovariectomized rats, but these effects were absent in gonadally intact middle-aged rats. Interestingly, only prolame induced anxiolytic- and antidepressant-like effects in middle-aged ovariectomized rats. Uterotrophic effects of prolame were weaker than E2 effects, notably in middle-aged females. Altogether, present data support the notion that prolame has the potential to be considered an EHRT with relevant psychoactive actions and with apparently lower adverse-side effects, especially in middle-aged populations.

Comparative Study of Bisphenol-A and its Analogue Bisphenol-S on Growth and Condition Factor of Juvenile Zebrafish (Danio rerio)

Bisphenol-A is a synthetic estrogen highly used in the production of polycarbonate plastics and epoxy resins in plastic industry world-wide. Bisphenol-A presents as a ubiquitous environmental contaminant in all ecosystems. Bisphenol-A is an endocrine disruptor which affects the growth, development and physiology of living organisms. Therefore, bisphenol-S has been introduced as a safe alternative to bisphenol-A and it has become the widely used bisphenol-A substitute. Bisphenol-S has also been identified as an endocrine disruptor and emerging environmental contaminant. Therefore the safety of bisphenol-S substitution has become questionable. Thus, this study was carried out to comparatively assess the impacts of bisphenol-A and bisphenol-S exposure on growth and condition factor of zebrafish (Danio rerio). After 7-days acclimatization period, twenty juvenile zebrafish of 67 dpf (days post fertilization) of age were treated 35 days with 10 μg/L and 100 μg/L of bisphenol-A, bisphenol-S and with treatment control in triplicate tanks. Mean body length, weight, specific growth rate and condition factor of fish were evaluated. Mean body weight increment of zebrafish under 100 μg/L of bisphenol-S and bisphenol-A were significantly different from the treatment control (p<0.05, One way ANOVA, Tukeys pairwise Comparison). The mean body length increment and specific growth rate were not significant under both concentrations of bisphenol-S and bisphenol-A with treatment control (p>0.05). However, the condition factor of fish under both concentrations of bisphenols were significantly less than control (p<0.05). The condition factor of fish under comparable concentrations of bisphenol-S and bisphenol-A were not statistically significant. Therefore, it can be concluded that exposure to environmental concentrations of both types of bisphenols could affect the wellbeing of juvenile zebrafish. Based on the findings, bisphenol-S cannot be recommended as a safe substitution to bisphenol-A. Yet, more comprehensive studies are recommended to evaluate relative effect of bisphenol-S on freshwater ecosystem health. 
 Keywords: Body length, Body weight, Condition factor, Bisphenol-A, Bisphenol-S, Zebrafish, (Danio rerio)

Estrogen contamination increases vulnerability of amphibians to the deadly chytrid fungus

Aquatic contaminants and infectious diseases are among the major drivers of global amphibian declines. However, the interaction of these factors is poorly explored and could better explain the amphibian crisis. We exposed males and females of the Brazilian Cururu Toad, Rhinella icterica, to an environmentally relevant concentration of the estrogen 17-alpha-ethinylestradiol (an emerging contaminant) and to the chytrid infection (Batrachochytrium dendrobatidis), in their combined and isolated forms, and the ecotoxicity was determined by multiple biomarkers: cutaneous, hematological, cardiac, hepatic, and gonadal analysis. Our results showed that Cururu toads had many physiological alterations in response to the chytrid infection, including the appearance of cutaneous Langerhans's cells, increased blood leukocytes, increased heart contraction force and tachycardia, increased hepatic melanomacrophage cells, which in turn led to gonadal atrophy. The estrogen, in turn, increased the susceptibility of the toads to the chytrid infection (higher Bd loads) and maximized the deleterious effects of the pathogen: reducing leukocytes, decreasing the contraction force, and causing greater tachycardia, increasing hepatic melanomacrophage cells, and leading to greater gonadal atrophy, which were more extreme in females. The exposure to estrogen also revealed important toxicodynamic pathways of this toxicant, as shown by the immunosuppression of exposed animals, and the induction of the first stages of feminization in males, which corroborates that the synthetic estrogen acts as an endocrine disruptor. Such an intricate relationship is unprecedented and reinforces the importance of studying the serious consequences that multiple environmental stressors can cause to aquatic populations.

Phytoestrogen: A protective shield for post-menopausal symptoms and breast cancer risk

Menopause is a physiological unavoidable condition in women’s life which leads to vasomotor, psychological, urogenital and chronic diseases collectively termed as post-menopausal symptoms (PMS). Hormone replacement therapy (HRT) is conventional line of treatment for treating PMS in which estrogens replacement is major choice for better therapeutic efficacy against symptoms like hot flushes, osteoporosis, hormonal balances, insomnia, obesity etc. However, estrogen is reported risk factor for breast cancer. The review discusses Ayurveda based strategies for management of PMS with phytoestrogen herbs, diet, lifestyle modification, de-addiction measures, yoga, aroma therapies etc. supported by evidence-based documentation.Herbs namely Dhanyaka (Coriander sativum), Manjishtha (Rubia cordifolia L), Chandana (Santalum album L), Ashwagandha (Withania somnifera L. Dunal), Jatamansi (Nardostachys jatamansi DC), Shatavari (Asparagus racemosus L), Kumari (Aloe vera L), Yashtimadhu (Glycyrrhiza glabra L), Haridra (Curcuma longa L), Triphala (Combination of fruits of Haritaki, Bibhitak, Amalaki in the proportion 1:2:4), Gokshura (Tribulus terrestris L), Arjuna (Terminalia Arjuna L.), Guduchi (Tinospora cordifolia L.), Ela (Elettaria cardamomum L), Narikela (Coccus nucifera L), Masha (Phaseolus vulgaris L), Mudga (Vigna radiata L). Shunthi (Zinziber officinale Roxb), Methika (Trigonella foenumgraecum L), Tila (Sesamum indicum L) are the natural sources of phytoestrogens. Phytoestrogen don’t exert side effects like synthetic estrogen molecules. These herbs are useful for management of various symptoms of PMS. Having anti-cancer potential against breast carcinoma these are useful for prevention of risk of breast cancer.

Nature based solutions for removal of steroid estrogens in wastewater.

Estrogens are a growing problem in wastewater discharges because they are continuously entering the environment and are biologically active at extremely low concentrations. Their effects on wildlife were first identified several decades before, but the environmental limits and the remedial measures are still not completely elucidated. Most conventional treatment processes were not designed with sufficiently long retention times to effectively remove estrogens. Nature-based wastewater treatment technologies such as treatment wetlands (TW) and high-rate algal ponds (HRAP) are economically feasible alternatives for decentralized wastewater treatment and have promise for removing steroid hormones including estrogens. For small communities with populations below 50,000, the overall cost of TWs and HRAPs is considerably lower than that of advanced decentralized treatment technologies such as activated sludge systems (AS) and sequencing batch reactors (SBR). This results from the simplicity of design, use of less materials in construction, lower energy use, operation and maintenance costs, and operation by non-skilled personnel. The nature-based technologies show high removal (>80%) for both natural and synthetic estrogens. Estrogen removal in TWs can be enhanced using alternative media such as palm mulch, biochar, and construction wastes such as bricks, instead of traditional substrates such as sand and gravel. While TWs are effective in estrogen removal, they have the disadvantage of requiring a relatively large footprint, but this can be reduced by using intensified multilayer wetland filters (IMWF). Using filamentous algae in HRAP (high-rate filamentous algal pond; HRFAP) is an emerging technology for wastewater treatment. The algae supply oxygen via photosynthesis and assimilate nutrients into readily harvestable filamentous algal biomass. Diurnal fluctuations in oxygen supply and pH in these systems provide conditions conducive to the breakdown of estrogens and a wide range of other emerging contaminants. The performance of these nature-based systems varies with seasonal changes in environmental conditions (particularly temperature and solar irradiation), however a greater understanding of operating conditions such as loading rate, hydraulic retention time (HRT), pond/bed depth, dissolved oxygen (DO) concentration and pH, which influence the removal mechanisms (biodegradation, sorption and photodegradation) enable TWs and HRAPs to be successfully used for removing estrogens.

Occurrence and environmental risk assessment of 4 estrogenic compounds in surface water in Belgiumin the frame of the EU Watch List.

The presence of natural estrogens estrone (E1), 17β-estradiol (E2), estriol (E3) and synthetic estrogen 17α-ethynylestradiol (EE2) in the aquatic environment has raised concerns because of their high potency as endocrine disrupting chemicals. The European Commission (EC) established a Watch List of contaminants of emerging concerns including E1, E2 and EE2. The proposed environmental quality standards (EQSs) are 3.6, 0.4, 0.035ng/L, for E1, E2, EE2, respectively. A thorough evaluation of analytical procedures developed by several studies aiming to perform sampling campaigns in different European countries highlighted that the required limits of quantification in surface water were not reached, especially for EE2 and to a lesser extent for E2. Moreover, data regarding the occurrence of these contaminants in Belgian surface water are very limited. A sampling campaign was therefore performed on a wide range of rivers in Belgium (accounting for a total of 63 samples). The detection frequencies of E1, E2, E3 and EE2 were 100, 98, 86 and 48%, respectively. E1 showed the highest mean concentration (= 4.433ng/L). In contrast, the mean concentration of EE2 was 0.042ng/L. The risk quotients (RQs) were calculated based on the respective EQS of each analyte. The frequency of exceedance of the EQS was 31.7% for E1, EE2, while it increased to 44.4% for E2. The extent of exceedance of the EQS, represented by the 95th percentile of the RQ dataset, was higher than 1 for E1, E2, EE2. The use of a confusion matrix was investigated to try to predict the risk posed by E2, EE2, based on the concentration of E1.