Estrogenic Properties Research Articles

Does Vitamin E Supplementation Alter Hormonal Levels in Polycystic Ovary Syndrome: A Systematic Review of Randomized Controlled Trials

Background: Vitamin E influences hormonal parameters in women, but the evidence concerning its effectiveness in polycystic ovarian syndrome (PCOS) are constrained. Objective: The objective of this systematic review is to perceive the mechanism behind the hormonal effects of vitamin E in PCOS and explore the effectiveness of vitamin E by analyzing the clinical studies. Methods: Electronic bibliographic databases, such as PubMed, Scopus, ProQuest, DOAJ, ScienceDirect, and Cochrane Library, were searched for clinical studies scrutinizing the effect of vitamin E supplementation on PCOS. The systematic review protocol is registered in PROSPERO (CRD42021272963) and was performed as per the PRISMA guidelines. Records analyzing the hormonal parameters were included. For individual study, the risk of bias was ascertained with NHLBI protocol for controlled randomized studies. Results: There were 1438 records identified, of which seven records were retrieved which met the inclusion criteria. Bibliographic details, number of participants, the dose of vitamin E, duration of the treatment and trial, parameters analyzed, and outcome of each study were extracted comprehensively. In the review, the majority of the studies embraced high-quality studies, which included double-blinded controlled trials, open-label controlled studies, and cohort studies. Conclusion: Vitamin E implies having a progesterone-like impression with estrogenic and androgenic properties. Furthermore, the ability of vitamin E as an antioxidant is also advantageous in PCOS women. However, there is a lack of empirical evidence on its mechanism, and the inadequacy of large-scale concerns about different age groups against PCOS is requisite.

Phosphorylation of Zearalenone Retains Its Toxicity.

Microbial biotransformation of Zearalenone (ZEN) is a promising deactivation approach. The residual toxicity and stability of Zearalenone-14-phosphate (ZEN-14-P) and Zearalenone-16-phosphate (ZEN-16-P), two novel microbial phosphorylation products of ZEN, remain unknown. We investigated the cytotoxicity, oxidative stress, proinflammatory, and estrogenic activity of phosphorylated ZENs using porcine intestinal cells, uterine explants, and human endometrial cells and traced their metabolic fate by liquid chromatography-tandem mass spectrometry (LC-MS)/MS analysis. The phosphorylated ZENs significantly decreased the viability of the IPEC-J2 and Ishikawa cells. Similar to ZEN, phosphorylation products induced significant oxidative stress, activated the expression of proinflammatory cytokines, and demonstrated estrogenic activity through upregulation of estrogen-responsive genes, activation of alkaline phosphatase, and proliferation of endometrial glands. LC-MS/MS analysis pointed out that although phosphorylated ZENs are partially hydrolyzed to ZEN, their respective metabolic pathways differ. We conclude that phosphorylation might not be sufficient to detoxify ZEN, leaving its cytotoxic, proinflammatory, and estrogenic properties intact.

Selenium ameliorates oxidized phospholipid-mediated testicular dysfunction and epididymal sperm abnormalities following Bisphenol A exposure in adult Wistar rats.

Bisphenol A (BPA) is an endocrine-disrupting compound extensively utilized in the production of polycarbonate polymers and epoxy resins that, upon exposure, pose a significant threat to male reproductive health because of its estrogenic properties. Accumulating evidence suggests that BPA exposure disrupts the normal process of spermatogenesis, alters testicular morphology and function, and interferes with testicular steroidogenesis and hormonal signaling. However, the precise mechanism by which BPA affects testicular function remains unclear. In this study, we explored the mechanism underlying BPA-induced testicular abnormalities and evaluated the protective effects of Selenium (Se). Thirty-two adult male albino Wistar rats were divided into four groups, and BPA was administered at 50mg/kg body weight, with or without Se supplementation, for 30 days. Se supplementation (2.5mg/kg body weight) was initiated 1 week before BPA administration. BPA administration resulted in alterations in testicular architecture, characterized by basement membrane disintegration in the seminiferous tubules, reduced spermatogenic cell counts, and increased interstitial tubule noncellular space. Furthermore, BPA exposure increased the levels of oxidized phospholipids, lipid peroxides, and hydroxyl radicals and decreased the activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. In addition, BPA significantly reduced the activities of 3β- and 17β-hydroxysteroid dehydrogenases, interfering with testicular steroidogenesis. In rats, coadministration of Se and BPA reduced the levels of oxidized phospholipids and increased the activities of antioxidant enzymes, leading to improved testicular function and epididymal sperm parameters, suggesting that Se plays a critical role in alleviating endocrine disruptor-induced testicular dysfunctions in rats.

Administration of Young Coconut (Cocos nucifera L.) Juice Ameliorates Memory Impairment in a Menopausal Rat Model.

In Southeast Asia, the traditional use of young coconut (Cocos nucifera L.) juice (YCJ) by women to alleviate postmenopausal symptoms suggests potential estrogenic properties. However, few studies explore the impact of YCJ on pathologies associated with estrogen deficiency in postmenopausal animal models. This study examines the impact of YCJ supplementation on memory impairment and depression-like behavior in ovariectomized (Ovx) rats. Ten-week-old female rats underwent either a sham operation (Sham) or bilateral Ovx. The rats in the Ovx + YCJ group received 5×-concentrated YCJ by gavage at a dose of 15 mL/kg body weight. Twelve weeks later, the Morris water maze and forced swim tests were used to evaluate hippocampus-dependent spatial memory and depression-like behavior, respectively. The Ovx rats displayed significant memory impairment (p < 0.05) and depression-like behaviors (p < 0.05), while the memory performance in the rats in the Ovx + YCJ group resembled that of the Sham rats. However, the administration of YCJ did not result in the improvement of depression-like behavior. These findings suggest that YCJ consumption may help ameliorate memory impairment in postmenopausal women.

An overview on the potential application of nanotechnology in enhancing the therapeutic efficacy of phytoestrogens

Phytoestrogens, derived from plants possesses structural similarity with 17 β-estradiol found in mammals. It is abundantly present in soybean along with red clove, alfalfa as well as other legumes, nuts, vegetables and seeds. It is used as hormone replacement therapy and exhibits both anti-estrogenic and estrogenic properties that linked to therapeutic benefits as well as plays active role in sports nutrition. Despite the potential benefits of phytoestrogens, their low solubility, bioavailability, and stability make it challenging to target them effectively. Recent advancements in nanotechnology have paved in facilitating target delivery. Scaling at nano level offered greater surface area, improved solubility, and bioavailability of phytoestrogens which has ultimately reduced the required medication dosage, and enhanced cost-effectiveness, particularly for expensive bioactive substances where precise dosages are recommended. The present article discussed about the potential application of nanotechnology in enhancing therapeutic benefits of phytoestrogens while minimizing their potential side effects.

Chronic disease management via modulation of cellular signaling by phytoestrogen Bavachin.

The emergence of chronic diseases, particularly cancers, cardiovascular, and bone disorders, presents a formidable challenge, as currently available synthetic drugs often result in significant side effects and incur higher costs. Phytoestrogen Bavachin, present in the Psoralea corylifolia L. plant, represents structural and functional similarity to mammalian estrogen and has recently attracted researchers for its medicinal properties. This review spotlighted the extraction methods, bioavailability and therapeutic interventions of Bavachin against diseases. Bavachin exerted estrogenic properties, demonstrating the ability to bind to estrogen receptors (ERs), mimicking the actions of human estrogen and initiating estrogen-responsive pathways. Bavachin delivered potent therapeutic ventures in abrogating chronic diseases, including cancer, neuronal, bone, cardiovascular, skin, lung, and liver disorders via targeting signaling transductions, managing calcium signaling, immune regulation, inflammation, apoptosis, and oxidative stress. In-silico analysis, including Gene ontology and pathway enrichment analysis, retrieved molecular targets of Bavachin, majorly cytochrome c oxidase (COX), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), and ER, hypothesizing Bavachin's cellular mechanism in preventing crucial health ailments. Limitations of Bavachin were also summarized, evidenced by hepatotoxicity at specific dosage levels. In conclusion, Bavachin showed promising therapeutic efficacy in suppressing chronic diseases and can be considered as an adequate replacement for hormone replacement therapy, necessitating further investigations on its effectiveness, safety, and clinical outcomes.

Cytotoxicity by endocrine disruptors through effects on ER Ca2+ transporters, aberrations in Ca2+ signalling pathways and ER stress.

Concerns regarding man-made organic chemicals pervading our ecosystem and having adverse and detrimental effects upon organisms, including man, have now been studied for several decades. Since the 1970s, some environmental pollutants were identified as having endocrine disrupting affects. These endocrine disrupting chemicals (EDC) were initially shown to have estrogenic or anti-estrogenic properties and some were also shown to bind to a variety of hormone receptors. However, since the 1990s it has also been identified that many of these EDC additionally, have the ability of causing abnormal alterations in Ca2+ signalling pathways (also commonly involved in hormone signalling), leading to exaggerated elevations in cytosolic [Ca2+] levels, that is known to cause activation of a number of cell death pathways. The major emphasis of this review is to present a personal perspective of the evidence for some types of EDC, specifically alkylphenols and brominated flame retardants (BFRs), causing direct effects on Ca2+ transporters (mainly the SERCA Ca2+ ATPases), culminating in acute cytotoxicity and cell death. Evidence is also presented to indicate that this Ca2+ATPase inhibition, which leads to abnormally elevated cytosolic [Ca2+], as well as a decreased luminal ER [Ca2+], which triggers the ER stress response, are both involved in acute cytotoxicity.

Interaction of Bisphenol A and Its Analogs with Estrogen and Androgen Receptor from Atlantic Cod (Gadus morhua).

The widespread use of bisphenol A (BPA) in polycarbonate plastics and epoxy resins has made it a prevalent environmental pollutant in aquatic ecosystems. BPA poses a significant threat to marine and freshwater wildlife due to its documented endocrine-disrupting effects on various species. Manufacturers are increasingly turning to other bisphenol compounds as supposedly safer alternatives. In this study, we employed in vitro reporter gene assays and ex vivo precision-cut liver slices from Atlantic cod (Gadus morhua) to investigate whether BPA and 11 BPA analogs exhibit estrogenic, antiestrogenic, androgenic, or antiandrogenic effects by influencing estrogen or androgen receptor signaling pathways. Most bisphenols, including BPA, displayed estrogenic properties by activating the Atlantic cod estrogen receptor alpha (gmEra). BPB, BPE, and BPF exhibited efficacy similar to or higher than that of BPA, with BPB and BPAF being more potent agonists. Additionally, some bisphenols, like BPG, induced estrogenic effects in ex vivo liver slices despite not activating gmEra in vitro, suggesting structural modifications by hepatic biotransformation enzymes. While only BPC2 and BPAF activated the Atlantic cod androgen receptor alpha (gmAra), several bisphenols exhibited antiandrogenic effects by inhibiting gmAra activity. This study underscores the endocrine-disrupting impact of bisphenols on aquatic organisms, emphasizing that substitutes for BPA may pose equal or greater risks to both the environment and human health.

Reduced estrogenic risks of a sunscreen additive: Theoretical design and evaluation of functionally improved salicylates

Salicylic esters (SEs), the widely used ultraviolet (UV) absorbers in sunscreen products, have been found to have health risks such as skin sensitization and estrogenic effects. This study aims to design SE substitutes that maintain high UV absorbance while reducing estrogenicity. Using molecular docking and Gaussian09 software for initial assessments and further application of a combination of two-dimensional and three-dimensional quantitative structure–activity relationships (2D-QSAR and 3D-QSAR, respectively) models, we designed 73 substitutes. The best-performing molecules, ethylhexyl salicylate (EHS)−5 and EHS-15, significantly reduced estrogenicity (44.54 % and 17.60 %, respectively) and enhanced UV absorbance (249.56 % and 46.94 %, respectively). Through screening for human health risks, we found that EHS-5 and EHS-15 were free from skin sensitivity and eye irritation and exhibited reduced skin permeability compared with EHS. Furthermore, the photolysis and synthetic pathways of EHS-5 and EHS-15 were deduced, demonstrating their good photodegradability and potential synthesizability. In addition, we analyzed the mechanisms underlying the changes in estrogenic effects and UV absorption properties. We identified covalent hydrogen bond basicity and acidity Propgen value for atomic molecular properties and the highest occupied molecular orbital eigenvalue as the main factors affecting the estrogenic effect and UV absorbance of SEs, respectively. This study focuses on the design and screening of SEs, exhibiting enhanced functionality, reduced health risks, and synthetic feasibility.

Estrogenic analysis of ten Thai medicinal plants used for treating menstrual irregularity by ERα and ERβ yeast two-hybrid systems

IntroductionSeveral traditional Thai medicinal plants have historically been utilised to alleviate menstrual irregularities. While it is hypothesised that phytoestrogens are pivotal in their medicinal efficacy, more empirical evidence is needed to verify this assumption. Furthermore, our understanding of the estrogenic effects mediated by estrogen receptors (ERα and ERβ) and their alterations post-intestinal enzymatic digestion is limited. This study aims to assess the estrogenic activity of 10 medicinal plants before and after in vitro simulated gastrointestinal digestion using yeast two-hybrid (Y2H) systems. MethodsY2H systems were constructed based on the interaction between the ligand-binding domain of estrogen receptors and the receptor interaction domain of coactivators. The medicinal plants were extracted in water at 95 °C for 1 hour or in 70% ethanol for 24 hours (1: 8 w/v). Their estrogenic activities before and after in vitro gastrointestinal digestion were determined using Y2H systems. ResultsThe majority of ethanol extracts exhibited higher estrogenic activity compared to water extracts, with detection notably facilitated by the ERβ-Y2H system. This study represents the first documentation of the estrogenic activities of Dendrolobium lanceolatum and Morinda coreia, both prominently identified by the ERβ-Y2H system. Specifically, the D. lanceolatum extract demonstrated the highest estrogenic activity, showing a significant enhancement following gastrointestinal enzymatic digestion, suggesting the presence of active metabolites. ConclusionsThese findings advance our understanding of the estrogenic properties of medicinal plants for treating menstrual irregularities, clarifying their effects on estrogen receptor subtypes and post-hydrolysis activities. Such insights are vital for determining their potential as alternative medicines.

Microwave-assisted bio-derived bismuth oxybromide (BiOBr) decorated polyaniline nanocomposite for highly sensitive electrochemical determination of endocrine disruptor bisphenol-A

In the presence of polyaniline (PANI), the novel nanocomposites of PANI-BiOBr bismuth oxybromide (BiOBr) were synthesized using a microwave-assisted green synthesis method and used to detect bisphenol A (BPA). By using fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and electrochemical methods, the hybrid PANI-BiOBr nanocomposite was confirmed. The higher conductivity, improve active surface-to-volume ratio, and enhanced electrochemical behaviour of the PANI-BiOBr nanoplatform can be attributed to the synergistic actions of PANI and BiOBr. With a high sensitivity of 11.7 μA (log nM)−1 cm2 and a low limit of detection of 0.19 × 10−9 μM, the constructed PANI-BiOBr sensor exhibits a broad linear range from 0.19 × 10−9 μM to 3.04 × 10−3 μM. In addition, this sensor produced adequate findings with outstanding selectivity, stability, repeatability, and reproducibility. Furthermore, the developed electrochemical PANI-BiOBr nanoplatform is essential in analysing real-world materials to detect BPA. The results obtained from these real sample analyses not only confirmed the effectiveness of the PANI-BiOBr nanocomposite sensor for BPA detection but also underscored its capability to detect other compounds with estrogenic properties, beyond just BPA.

(R)-(-)-Xanthorrhizol Inhibits the Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Matrix Metalloproteinases via the NF-κB Signaling Pathway.

(R)-(-)-xanthorrhizol is a bioactive sesquiterpenoid and major chemical constituent of Curcuma zanthorrhiza rhizomes. It was reported to have many pharmacological activities including nephroprotective, hepatoprotective, antimicrobial, anti-inflammatory, antioxidant, antihypertensive, antihyperglycemic, antiplatelet, estrogenic, and antiestrogenic properties. (R)-(-)-xanthorrhizol was also investigated for antiproliferative activity against many cancer cells including breast, lung, liver, ovarian, and colon cancer. It was also revealed to have a potential effect on TNBC cells MDA-MB-231. Considering the previous studies, this study has aimed to investigate the antimigratory and anti-invasive properties, as well as the possible molecular mechanisms, behind these properties. The findings of (R)-(-)-xanthorrhizol on MDA-MB-231 cell migration and invasion demonstrated significant inhibition at three different concentrations in a concentration-dependent manner, which was observed in the scratch, transwell migration, and invasion assays. Further investigation of the molecular mechanism using gelatin zymography revealed that (R)-(-)-xanthorrhizol prevented cell migration and invasion of breast cancer cells through the inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression. Western blot analysis indicated that the inhibition of matrix metalloproteinases is possibly the result of the inhibition of phosphorylation in the NF-κB signaling pathway. These findings corroborate (R)-(-)-xanthorrhizol to proceed for the further studies as a possible future drug candidate for cancer patients.

ANTIMICROBIAL ACTIVITY OF PIMPINELLA - AN OVERVIEW

Pimpinella species, belonging to Apiaceae (Lindl.) family, utilized in many fields of industry as spice, fruit, vegetable and beverage have especially been used in traditional medicine as a remedy in various countries. Essential oils (EO) of various species including Pimpinella cypria, Pimpinella kotshchyana, Pimpinella saxifraga, and Pimpinella anisum were reported to have antibacterial and antifungal activities. Furthermore, it was observed that P. anisum EO possessed antiviral properties. Along with its antimicrobial activity, Pimpinella species were found to have antioxidant, anti-inflammatory, anticonvulsant, antispasmodic, estrogenic, cytotoxic, insecticidal, and repellent properties. This review aims to provide an enhanced understanding on some Pimpinella species’ morphology, chemical constituent, industrial and medicinal usage, and antimicrobial activities against bacteria, fungi, and viruses.

Silkworm (Bombyx mori L.) Has Beneficial Effects on Menopausal Symptoms by Enhancing Estrogen Receptor Signaling in Ovariectomized Mice.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.

Aframomum subsericeum and Aframomum alboviolaceum leaf essential oils exhibit testosterone antagonistic and oestrogen synergic effects in male Wistar rats: potential candidates for prostate cancer treatment

Background: Aframomum species are routinely used as spices in many traditional Cameroonian meals due to their sweet fragrance. Many species of the Aframomum species are also used to treat cancer, pain, arthritis, and stomach disorders. This work was performed to determine the chemical composition, antiandrogenic, and estrogenic properties of Aframomum subsericeum and Aframomum alboviolaceum leaf essential oils. Methods: The chemical components of A. subsericeum and A. alboviolaceum essential oils were identified by gas chromatography-mass spectroscopy. The anti-androgenic and estrogenic properties were investigated in vivo in physically and chemically castrated Wistar rats, respectively. Results: Fifteen compounds versus nine compounds were identified in A. subsericeum and A. alboviolaceum essential oils, respectively. The main compounds of Aframomum subsericeum were cyclohexene, 1-methyl-4-(1-methylethylidene) (10.03%), γ-terpine (12.22%), and myrtenyl acetate (8.52%), while those of Aframomum alboviolaceum were γ-terpinene (20.07%), caryophyllene (11.58%), myrtenyl acetate (7.22%), and (1R)2, 6, 6 trimethylbicyclo [3.1.1] hept-2-ene (6.97%). The results of the anti-androgenic test reveal that both A. subsericeum and A. alboviolaceum induced a significant decrease in androgen-dependent organs, especially the prostate and seminal vesicle, at doses of 200 mg/kg and 100 mg/kg. Interestingly, A. alboviolaceum showed oestrogen synergic effects on the above organs. Conclusions: So, this study reveals mainly the presence of diterpenoids in both A. subsericeum and A. alboviolaceum, which are potential candidates for prostate cancer treatment. The in vivo results show that Aframomum leaf essential has antiandrogenic and oestrogen synergic properties, suggesting that the oils could provide a safe natural drug for prostate cancer treatment.

The Effect of Psoralea corylifolia (Babchi) on Neuronal Apoptosis Induced by Palmitate in PC12 Cells and its Role in Alzheimer’s Disease: A Review

Background: Psoralea corylifolia (PC) seed extract (PCE) has been extensively utilized as an herbal drug due to its favorable effects on human health. It’s extracts and active components have demonstrated a variety of biological actions including estrogenic, anticancer, antioxidant, anti-bacterial, anti-depressant, anti-inflammatory and anti-ageing properties. Purpose: A study of this medicinal herb has major constituents extracted using different plant parts has been depicted and among them, Bakuchiol has the highest ethyl acetate extract content. Methods: The mechanism behind PCE’s anti-lipotoxic activity against palmitate (PA)-induced lipotoxicity in PC12 cells was examined. Results: CE therapy not only raised the quantities of mRNA for antioxidant genes such as heme-oxygenase and nuclear factor (erythroid-derived 2)-like 2 but also lowered the production of reactive oxygen species caused by PA. Conclusion: Prenylflavonoids play a unique role in the treatment of Alzheimer’s disease (AD) and can be used as a nootropic agent. This article comprehensively enumerated the literature on the anti-apoptotic effects of PC and its potential pathogenesis in AD.

Preoperative topical estrogen application in the management of hypospadias: a systematic review.

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.

Estrogen-Containing Contraceptive Use and Blood Lead Concentrations in a Cohort of Young Women [ID 2683459

INTRODUCTION: Toxic metal lead is stored in the skeleton and, with increased bone turnover, is mobilized to systemic circulation. Given the bone-conserving properties of estrogens, we hypothesized that current users of estrogen-containing contraception would have lower blood lead concentrations. METHODS: We conducted a cross-sectional analysis using baseline data from the Study of Environment, Lifestyle &amp; Fibroids (SELF). During 2010–2012 (baseline), 1,693 self-identified Black women, ages 23–35, enrolled. Data on contraceptive use were ascertained by interview. We quantified lead concentrations in whole blood using inductively coupled plasma mass spectrometry (ICP-MS). Among 1,555 participants, we estimated the percent difference in blood lead concentrations and 95% CIs between current users and nonusers of estrogen-containing contraception using multivariable linear regression, adjusting for potential confounders. RESULTS: The geometric mean blood lead concentrations for estrogen-containing contraceptive users and nonusers were 0.41 micrograms/dL (95% CI: 0.39, 0.43) and 0.51 micrograms/dL (95% CI: 0.50, 0.52), respectively. After adjustment, current use of estrogen-containing contraception was associated with 10% lower blood lead concentrations (95% CI: −15%, −4%). Considering estrogen-containing contraceptive type, compared to nonusers, combined oral contraceptive users (n=187) had 9% lower blood lead concentrations (95% CI: −15%, −2%) and vaginal ring/transdermal patch users (n=33) had 17% lower blood lead concentrations (95% CI: −29%, −4%). CONCLUSION: As hypothesized, we observed lower blood lead concentrations with current use of estrogen-containing contraception. Further research is warranted to confirm the results and to understand the relationship between lead exposure, hormonal contraception, and bone health to limit systemic lead exposure.

Exploring the connection: endocrine disruptors and polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is heterogeneous endocrine disorder in females manifesting reproductive dysfunction and metabolic abnormalities. Endocrinopathy in the form of hyperandrogenism leading to alteration in clinical phenotype and fertility seen. Atherogenic dyslipidaemia and insulin resistance as a result of metabolic disturbance also encountered. Recent years, endocrine disrupting chemicals (EDCs) are widely studied and linked for their alleged role in the development of PCOS. EDCs like bisphenol A (BPA), Phthalate, methoxychlor and chlorpyrifos which are present in many industrial as well as daily use products poses risk of development of various diseases. This review discusses the role of EDCS specially BPA in the pathogenesis of PCOS with study of interest identified and extracted from databases like Pub Med and Google scholars using MeSH keywords. BPA has estrogenic property and binds to oestrogen receptors α and β. Stimulation of ovarian theca cells and dysregulation of steroid biosynthesis leads to androgen overproduction. It stimulates GnRH Pulse generator, decreasing the level of LH hence fertility is affected. BPA also interact with adipose tissue receptors and causes differentiation, lipid deposition and inhibition of adiponectin. Its serum and urinary levels are found to be elevated in PCOS patient. In animal studies, it is found that BPA exposure causes impaired folliculogenesis, insulin resistance and DNA methylation. EDC exposure, especially BPA which is an integral constituent of many industrial and daily use items may cause PCOS possibly by altering androgen synthesis, adipocyte stimulation and epigenetic modification.

Exploring the anti-osteoporosis potential of Petroselinum crispum (Mill.) Fuss extract employing experimentally ovariectomized rat model and network pharmacology approach

One of the most prevalent secondary osteoporosis is ovariectomy-induced osteoporosis. Parsley (Petroselinum crispum) has potent estrogenic and antioxidant properties and was used traditionally in the treatment of amenorrhea and dysmenorrhea. The present study aimed to characterize parsley leaf extract (PLE) employing RP-HPLC-MS-MS/MS-based method and possible protective effect in ovariectomized (OVX)-induced osteoporosis in rats was assessed. Rats were randomly assigned into SHAM group, OVX group, PLE + OVX group (150 mg/kg/day, p.o), and estradiol benzoate (E2) + OVX group (30 μg/kg/day, s.c). After eight weeks following ovariectomy, biomarkers of bone strength, bone resorption, oxidative stress and histopathology were carried out. A network pharmacology approach investigated the key targets and potential mechanisms by of PLE metabolites against osteoporosis using databases: PubChem, BindingDB server, DisGeNET, ShinyGO, and KEGG Pathway. Moreover, FunRich 3.1.3, Cytoscape 3.10.0, and MOE 2019.0102 softwares were used for network pharmacology analysis and molecular docking studies.Flavones and hydroxycinnamic acid derivatives were predominant among 38 metabolites in PLE. It significantly restored bone strength and bone resorption biomarkers, osteocalcin (OST), oxidative stress biomarkers and histopathological alterations. The employed network pharmacology approach revealed that 14 primary target genes were associated with decreasing the severity of osteoporosis. Molecular docking revealed that cGMP-PKG signaling pathway has the highest fold enrichment and its downstream PDE5A. Luteolin, diosmetin, and isorhamnetin derivatives affected mostly osteoporosis targets. PLE exhibited protective action against ovariectomy-induced osteoporosis in rats and may be a promising therapy for premenopausal bone loss. cGMP-PKG signaling pathway could be a promising target for PLE in treating osteoporosis.