Estrogen Research Articles

Association of SOX10 Immunohistochemical Expression with Triple Negative Breast cancer

Abstract Background: The term triple-negative breast cancer (TNBC) refers to a particular class of aggressive, poorly differentiated neoplasms that show the absence of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor2 (HER2) antibodies. The aim of this study is to assess the immunohistochemical expression of SOX10 in TNBC, its correlation with tumor grade and other clinicopathologic characteristics. Materials and methods: A Cross sectional study which included thirty paraffin blocks of primary (TNBC) , that were collected from Karbala teaching centre of histopathology in the period (from Jan. 2023 to Dec. 2023). For each of the collected block, two sections were taken. One stained by hematoxylin and eosin and the other was stained by immunohistochemical method for SOX10. Results: SOX10 reported positive in 43% (13) positive cases versus 57% (17) negative cases, this positivity was significantly correlated with pathological grade (p value =0.012) and the pathological stage (p value =0.038). A particular statistical significance was found in association with the lymph node group and distant metastasis. (p value 0.039 and 0.037) respectively. No significant statistical difference between SOX10 expression and the patient’s age, tumor size, presence of Ductal carcinoma in situ (DCIS) and lymphovascular invasion. Conclusion: The study suggested that SOX10 expression is a prognostic biomarker for TNBC. It also highlighted the clinical significance of targeting SOX10 as a promising potential therapeutic target gene for TNBC therapy. Keywords: SOX10; triple negative breast cancer; immunohistochemistry.

Bladder Outlet Obstruction Due to Recurrent Complete Labial Fusion in Postmenopausal Woman—Case Report

Background: Labial fusion is a rare condition typically observed in prepubescent girls, but it can also occur in postmenopausal women due to estrogen deficiency. Methods: Our case report presents a unique instance of recurrent complete labial fusion causing bladder outlet obstruction in a postmenopausal woman. Results: The 84-year-old patient presented with dysuria and intermittent urine leakage. A physical examination revealed complete labial fusion with a small central opening. The diagnosis was confirmed through clinical evaluation, and surgical intervention was necessary to relieve the obstruction. Recurrent episodes followed despite a hormonal treatment with topical estrogen. Conclusions: This case highlights the importance of early diagnosis and the challenge of managing labial fusion in postmenopausal women, where recurrent episodes may complicate treatment. Surgical management, along with hormone therapy, remain essential for optimal outcomes. Further studies are needed to understand the recurrence mechanisms and to establish standardized treatment protocols.

Genetic Evidence for Estrogenic Effects of Benzophenone-2 on Zebrafish Neurodevelopment and Its Signaling Mechanism.

Estrogens play a crucial role in regulating various biological responses during the early stages of neurodevelopment. Benzophenone-2 (BP2), a widely used organic ultraviolet (UV) filter, has been proven as an estrogenic compound, whereas the estrogenic effects of BP2 on neurodevelopment remain largely unknown. Here, we investigated the neurodevelopmental toxicity of BP2 by exposing zebrafish embryos from 2 to 120 h postfertilization (hpf) at environmentally relevant concentrations. We demonstrated that early life exposure to BP2 induced multiple concentration-dependent impairments in the nervous system, including hypoactivity, abnormal brain morphology, impaired neurocyte proliferation, shortened axon, and increased neurocyte apoptosis. Moreover, metabolomic profiling revealed a decrease in dopamine (DA) and its metabolites in BP2-treated larvae. Using E2 treatment and morpholino knockdown assays, we provided strong genetic evidence that the BP2-induced behavioral disorders were associated with estrogen-dependent signaling, especially estrogen receptors 2a and 2b (esr2). Subsequently, transcriptomic profiling indicated that the activation of esr2 further inhibited the expression of LIM homeobox transcription factor 1 β a (lmx1ba), which is vital for normal neurodevelopment. Consistently, the overexpression of lmx1ba and inhibition of esr2 obviously alleviated BP2-caused neurotoxicity, uncovering a seminal role of esr2 and lmx1ba in BP2-induced neurodevelopmental toxicity. Our findings provide the first evidence in fish that BP2 can induce neurodevelopmental deficits and brain dysfunction and offer novel insights into the mechanisms of toxicity of BP2 as well as other emerging benzophenones.

Exploring the impact of 3,3’-diindolylmethane on the urinary estrogen profile of premenopausal women

Background3,3’-diindolylmethane (DIM) is a phytonutrient derived from cruciferous vegetables that is an often-used supplement in the complementary and alternative medicine space. The most common goal for providers when recommending DIM to their patients is to alter estrogen metabolism, yet research into DIM’s effect on the estrogen profile is lacking in the published literature. The objective of this study was to comprehensively evaluate DIM’s effect on the urinary estrogen profile.MethodsIn this retrospective cohort study, we analyzed data from a clinical laboratory, including urinary estrogen and estrogen metabolite concentrations. Analyte concentrations were determined from dried urine samples using a gas chromatography-tandem mass spectrometry assay. Individuals were separated into two groups, either reporting taking DIM (N = 909) or reporting not taking DIM (N = 18,385). Comparisons between individuals in these two groups were made using the Wilcoxon rank sum test. Additionally, we were also able to explore a subset of women who had laboratory results in the database before and after initiating DIM treatment (N = 53). In this subset, differences were assessed with Wilcoxon signed rank tests.ResultsIn the larger group that was separated into women reporting either DIM use or no use, significant differences were observed in the concentrations of almost every urinary estrogen and estrogen metabolite (with the only exception being 2-methoxyestrone) in the urinary estrogen profiles of those taking DIM compared to those not taking DIM (all P values < 0.001). In the smaller subset of individuals with results before and after initiating DIM use, differences were only seen in 4 of the urinary estrogens and estrogen metabolites (P < 0.001 for estrone, estradiol, estriol, and 16-hydroxyestrone). Differences in total estrogens were significant in both the larger group and the smaller subset (both with P < 0.001). Additionally, observed differences in the ratios of metabolites followed a similar trend with more significant differences observed in the larger group. Notably, the 2-hydroxyestrone:16-hydroxyestrone ratio increased significantly in both the larger group and the smaller subset with results before and after DIM use.ConclusionsThe results of this study provide the most comprehensive evaluation to date of DIM’s effect on the urinary estrogen profile. Additionally, the results demonstrate that the dried urine collection and accompanying assay used capture changes that are similar in direction, but not necessarily magnitude, to previous reports in the literature. Considered together, these two things highlight the clinical validity and utility of this approach to the evaluation of DIM supplementation and suggest the need for additional studies using this approach to fully understand the potential clinical utility of DIM.

GPER1 activation by estrogenic compounds in the inflammatory profile of breast cancer cells

Breast cancer (BC) is the most frequent female neoplasm worldwide. Its establishment and development have been related to inflammatory cytokine expression. Steroid hormones such as estradiol (E2) can regulate proinflammatory cytokine secretion through interaction with its nuclear receptors. However, little is known regarding the activation of its membrane estrogen receptor (GPER1) and the inflammatory cytokine environment in BC. We have studied the synthesis and biological effects of molecules analogs to E2 for hormone replacement therapy (HRT), such as pentolame. Nevertheless, its interaction with GPER1 and the modulation of inflammatory cytokines in different BC types has been barely studied and deserves deeper investigation. In this research, the role of GPER1 in the proliferation and modulation of inflammatory cytokines involved in carcinogenesis and metastatic processes in different BC cell lines was assessed by binding to various compounds. To achieve this goal, the presence of GPER1 was identified in different BC cell lines. Subsequently, cell proliferation after exposure to E2, pentolame and GPER1 agonist, G1, was subsequently determined alone or in combination with the GPER1 antagonist, G15. Finally, the pro-inflammatory cytokine secretion derived from the supernatants of BC cells exposed to the previous treatments was also assessed. Interestingly, GPER1 activation or inhibition has significant effects on the cytokine regulation associated with invasion in BC. Notably, pentolame did not induce cell proliferation or increase the proinflammatory cytokine expression compared to E2 in BC cell lines. In addition, pentolame did not induce the presence of the cell adhesion molecule PECAM-1. In contrast, E2 treatment weakly induced the expression of PECAM-1 in MCF-7 and HCC1937 cells, and G1 treatment showed this effect only in MCF-7 cells. The results suggest that GPER1 might be a significant inflammatory modulator with angiogenic-related effects in BC cells. In addition, pentolame might represent an HRT alternative in patients with BC predisposition.

Identifying Herbal Candidates and Active Ingredients Against Postmenopausal Osteoporosis Using Biased Random Walk on a Multiscale Network.

Postmenopausal osteoporosis is a major global health concern, particularly affecting aging women, and necessitates innovative treatment options. Herbal medicine, with its multi-compound, multi-target characteristics, offers a promising approach for complex diseases. In this study, we applied multiscale network and random walk-based analyses to identify candidate herbs and their active ingredients for postmenopausal osteoporosis, focusing on their underlying mechanisms. A dataset of medicinal herbs, their active ingredients, and protein targets was compiled, and diffusion profiles were calculated to assess the propagation effects. Through correlation analysis, we prioritized herbs based on their relevance to osteoporosis, identifying the top candidates like Benincasae Semen, Glehniae Radix, Corydalis Tuber, and Houttuyniae Herba. Gene Set Enrichment Analysis (GSEA) revealed that the 49 core protein targets of these herbs were significantly associated with pathways related to inflammation, osteoclast differentiation, and estrogen metabolism. Notably, compounds such as falcarindiol from Glehniae Radix and tetrahydrocoptisine from Corydalis Tuber-previously unstudied for osteoporosis-were predicted to interact with inflammation-related proteins, including IL6, IL1B, and TNF, affecting key biological processes like apoptosis and cell proliferation. This study advances the understanding of herbal therapies for osteoporosis and offers a framework for discovering novel therapeutic agents.

Identification of Estrogen-Responsive Proteins in Mouse Seminal Vesicles Through Mass Spectrometry-Based Proteomics.

Background: Although estrogenic compounds promise therapeutic potential in treating various conditions, concerns regarding their endocrine-disrupting effects have been raised. Current methodologies for screening estrogenicity in rodent models are limited to the female-specific uterotrophic bioassay. Studies have reported enlargement of the seminal vesicles in orchiectomized males treated with estrogens. However, identifying estrogenicity strictly through changes in wet weights is uninformative regarding the molecular mechanisms of these agents. Therefore, protein-based biomarkers can complement and improve the sensitivity of weight-based assessments. To this end, we present a discovery-driven proteomic analysis of 17β-estradiol's effects on the seminal vesicles. Methods: We treated orchidectomized mice with the hormone for five days and used the vehicle-treated group as a control. Seminal vesicles were analyzed by shotgun approach using data-dependent nanoflow liquid chromatography-tandem mass spectrometry and label-free quantification. Proteins found to be differentially expressed between the two groups were processed through a bioinformatics pipeline focusing on pathway analyses and assembly of protein interaction networks. Results: Out of 668 identified proteins that passed rigorous validation criteria, 133 were regulated significantly by 17β-estradiol. Ingenuity Pathway Analysis® linked them to several hormone-affected pathways, including those associated with immune function such as neutrophil degranulation. The altered protein interaction networks were also related to functions including endocrine disruption, abnormal metabolism, and therapeutic effects. Conclusions: We identified several potential biomarkers for estrogenicity in mouse seminal vesicles, many of them not previously linked with exogenous 17β-estradiol exposure.

Fertility protective effects of Brillantaisia patula leaf extract against cyclophosphamide-induced ovarian damage in Wistar rats

BackgroundThe primary indication of infertility is the incapacity to conceive, and in females, the majority of instances of female infertility stem from ovulation disorders. This study evaluated the female fertility-enhancing effects and safety of aqueous leaf extract of Brillantaisia patula (ALEBP) in a cyclophosphamide (CYP) model of sterility in Wistar rats.MethodSixty-six female rats randomly allotted to six groups (n = 11) were administered with the appropriate regimen for 21 days and then mated with male rats. Group 1 (control) received distilled water. Groups 2–6 were treated with a single dose (200 mgkg− 1 body weight) of cyclophosphamide intraperitoneally and, in addition, received the same volume (0.5 mL) of distilled water, 18, 36, 72 mgkg− 1 body weight of ALEBP and 200 mg per body weight of vitamin C orally. Mating lasted 11 days; on day 20, the female Wistar rats were sacrificed. Data were analysed using One-way Analysis of Variance (ANOVA) followed by Dunett’s posthoc analysis, and GraphPad (at p < 0.05).ResultsResults herein showed that ALEBP significantly (p < 0.05) increased the diminution in activities/levels of glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity (TAC), cholesterol, alkaline phosphatase (ALP), acid phosphatase (ACP), estrogen (ES), and luteinising hormone (LH) induced by cyclophosphamide. ALEBP further reversed the increased level of malondialdehyde (MDA), tumour necrosis factor-α (TNFα), interleukin 8 (IL-8), and follicle-stimulating hormone (FSH) caused by cyclophosphamide (p < 0.05). In addition, ALEBP, while it significantly increased the cyclophosphamide-induced reduction in the number of implantations in each animal, the total number of viable fetuses, the total number of corpora lutea, and the fertility index, also significantly reduced the number of fetal resorptions in each animal and pre-implantation loss that was increased by cyclophosphamide. Moreover, the cyclophosphamide-induced degenerative and necrotic changes in the ovarian cells and uterus were reversed by ALEBP.ConclusionsConsidered as a whole, the aqueous leaf extract of Brillantaisia patula reversed oxidative stress and inflammatory side effects of cyclophosphamide, preserving ovarian function and fertility in the rats. This may suggest its exploration as a safe agent against toxic side effects of chemotherapy and fertility-related disorders of the uterus and ovary.

Service evaluation: HRT regimens prescribed for complex menopausal patient cases

Abstract Introduction With government and NHS drivers, there has been an increase in menopause awareness and management. The NHS Business Services Authority reported a 29% increase in hormone replacement therapy (HRT) prescribing between 2022-2023, with expectation that this would rise further with introduction of the new HRT prepayment certificate in April 20231. Partly due to celebrity sway and supported by national guidance2,3 there is patient expectation towards transdermal oestrogen with natural progesterone HRT. Older women, some years since undergoing natural menopause, are also seeking advice on HRT use (3) with referrals accepted by specialist menopause clinics. Aims This service evaluation project was undertaken to evaluate the prescribing of HRT regimens in complex patient cases seen within a specialist menopause clinic and included assessment of those advised to use natural progesterone as part of their HRT regimen, for endometrial protection2,3. Method 366 specialist menopause clinic appointments over 6 months (05.01.23-22.06.23) were retrospectively evaluated, with patients seen by a multidisciplinary team within an outpatient secondary care setting. Exclusion criteria included appointments not attended, those that were incorrectly booked or patients with inaccessible records. Data was collected using electronic patient records with results analysed using Microsoft Excel. Results Of 327 (89%) appointments evaluated, the patient age ranged between 30-84 years (median age 53). HRT was recommended for 288 (88%) patients. HRT was not recommended in cases such as antiphospholipid syndrome, breast cancer without genitourinary symptoms, in those of advanced age or in line with patient choice with patient decision not to take HRT after an individualised risk benefit evaluation. For 26 (9%) patients, only topical oestrogen treatment for localised genitourinary syndrome symptoms was advised. 171 (52%) patients were postmenopausal, 61 (19%) perimenopausal, 46 (14%) with premature ovarian insufficiency and 20 (6%) with surgical menopause. For 22 patients (7%) with Mirena intra-uterine system in situ, their menopause phase could not be accurately defined. 243 (88%) of those recommended HRT were advised a combined regime; 154 (53%) continuous combined; 67 (23%) sequential combined and 22 (9%) oestrogen with Mirena coil. For patients accepting combined HRT, one third (81) were recommended natural progesterone, with the other patients using progestogens for endometrial protection. Of these 81 patients, 77 (95%) were recommended transdermal oestrogen in combination with natural progesterone. For patients recommended natural progesterone, 68 (84%) were for doses in line with licensing and current British Menopause Society guidance. For 10 patients the off-label recommendation involved doubled doses of natural progesterone to help with control of unfavourable bleeding. Discussion For prescribing of natural progesterone, we assumed that our recommendations to the GP were enacted. With retrospective evaluation of patient letters as a limitation, this project identified that within our specialist clinic complex patient population, a recommendation for natural progesterone was made for one third of patients suitable for combined HRT use. When not prescribed in line with licensing, this was due to issues with vaginal bleeding. Acknowledgments Biranavi Kirupakaran, Sahil Misri, Hernani Almeida, Medical Students, Imperial College London for data collection.

Evaluating the estrogen degradation potential of laccase and peroxidase from Bacillus ligniniphilus L1 through integrated computational and experimental approaches

This study investigated the degradation potential of laccase and catalase-peroxidase from the extremophilic marine bacterium Bacillus ligniniphilus L1 against endogenous and synthetic estrogen compounds using an integrated computational and experimental approach. Molecular docking identified five estrogen compounds exhibiting reliable bindings with enzymes, which were then subjected to enzyme activity assays. The degradation potential of the two enzymes against five selected estrogen compounds were investigated and compared with their commercial counterparts. Laccase from L1 showed higher degradation potential against estrone (47.02 % without and 62.21 % with ABTS) compared to commercial laccase (39 % without and 54.20 % with ABTS). For estradiol valerate, commercial laccase showed a slightly higher degradation (52.47 %) than L1 laccase (49.94 %), but with ABTS, L1 laccase performed better (74.15 % vs. 68.03 %). Notably, L1 catalase-peroxidase demonstrated significantly higher degradation for all tested compounds compared to its commercial counterpart with efficiencies of 96.16 %, 89.09 %, 74.94 %, 64.91 %, and 62.80 % against estropipate, quinestrol, estradiol valerate, estriol and estrone, respectively, revealing its potential for commercial applications. Molecular dynamics simulations revealed the interaction and stability of enzyme-estrogen complexes, with MMGBSA binding energy calculations supporting experimental results. These findings highlight the usefulness of the computational approach in elucidating the molecular mechanisms underlying enzyme-mediated bioremediation of environmental contaminants.

Vaginal LASER and estrogen comparison in Genitourinary Syndrome of Menopause

Aim:This study aims to compare the efficacy of CO2 fractionated laser therapy and topical estrogen treatment in managing Genitourinary Syndrome of Menopause (GSM). Materials and Methods:A total of 88 patients diagnosed with GSM were included in this retrospective study. Of these, 39 received CO2 fractionated laser treatment, while 49 were treated with topical estrogen. Patients whose treatment was completed 1 to 1.5 months prior and had pre-treatment Vaginal Health Index (VHI) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scored recorded were included in the study. These patients were invited for a follow-up visit, during which post-treatment VHI and ICIQ-SF scores were assessed by a physician. Results:Both the laser and estrogen groups showed significant improvements in VHI and ICIQ-SF scores after treatment (p < 0.00001 for both groups). No statistically significant difference was found between the post-treatment VHI and ICIQ-SF scores of the two groups (p < 0.923 and p < 0.579, respectively). Conclusion:Although there was no significant difference in the treatment efficacy between estrogen and CO2 fractionated laser therapy, there was a considerable difference in cost, with CO2 fractionated, with laser treatment being 23–24 times more expensive. Therefore, CO2 fractionated laser therapy, which shows similar short-term efficacy to topical estrogen, may be more suitable for patients where hormone therapy is contraindicated.

The Association of Mammographic Breast Density and Breast Cancer Biology Among Breast Cancer Women in Jordan

Background: A breast mammogram is considered the gold standard modality for breast cancer screening. The sensitivity of breast mammograms is highly linked to mammographic breast density (MBD) which is strongly linked to women's age, ethnicity, and other factors. Higher breast density is considered one of the risk factors for breast cancer development and it can be associated with different pathological and biological features of breast cancer. Methods: This is a retrospective review of 97 women with a diagnosis of breast cancer in a tertiary hospital in Jordan who were diagnosed in the period between 2018 and 2020. We compared patients with a positive status for estrogen (ER) or progesterone (PR) receptors (ER+/PR+) and others with negative receptors (ER-/PR-), in terms of their correlation with MBD. Results: The analysis has included 97 patients. Of which, 87.6% had either a PR+ or an ER+, and 38.1% of patients were positive for HER2/neu protein. The sample mean age was 56.4 and most patients were obese (56.7%). MBD of our cohort was 30.9% (30/97) fatty, 29.9% (29/97) scattered, 23.7% (23/97) heterogeneously dense, and 15.5% (15/97) dense. The ER+/PR+ group was more associated with fatty (35.3% vs 0.0%) and scattered (31.8% vs 25.0%) MBD types than the ER-/PR- group, and less associated with the dense type (9.4% vs 58.3%), and the association was statistically significant (P &lt; 0.001). However, no statistically significant correlation was found between MBD and the HER2/neu protein status. Conclusion: According to our results, ER+/PR+ group patients tend to have fatty and scattered MBD types than the ER-/PR- patients. Larger randomized cohorts should investigate the association between breast cancer biological subtypes and MBD.

Protein expression of estrogen, progesterone, and human epidermal growth factor receptors in young Iraqi women with breast cancer

Breast cancer is currently evaluated by the presence of hormonal receptors in the tumor tissue, which are among the most important prognostic and predictive markers used at present. The current study was conducted in Thi-Qar Governorate (Iraq) on women aged 20-40 years who have breast cancer (BC), highlighting­ the spread of this disease among young groups. The expression of estrogen (ER), progesterone (PR), and human epidermal growth factor (Her2/neu) receptors in breast tissues using immunohistochemical analysis was estimated. Breast tissue samples were collected from patients undergoing breast surgery and biopsy. Formalin-fixed paraffin-embedded samples were divided into BC (80), and control (20) groups. The study found that protein expression of both ER and PR was positive in 87.5% and negative in 12.5%, Her2/neu positive in 60% and negative in 40% of BC samples. The subtypes identified were luminal A (58.75%), luminal B (31.25%), HER2-positive (6.25%), and triple-negative (3.75%) BC. The high percentage of luminal A molecular subtype of BC is considered a good prognosis and treatable by anti-hormonal therapy. Keywords: breast cancer, estrogen, human epidermal growth factor, immunohistochemistry, progesterone, receptors

Endometrial Dysbiosis: A Possible Association with Estrobolome Alteration

Background/Objectives: Microbiota modification at the endometrial level can favor gynecological diseases and impair women’s fertility. The overgrowth of pathogen microorganisms is related to the contemporary alteration of estrogen-metabolizing bacteria, including β-glucuronidase, thereby enhancing estrogen-related inflammatory states and decreasing anti-inflammatory cells. The possible connection between estrobolome impairment and gynecological diseases has been suggested in animal models. Nevertheless, in humans, coherent evidence on the estrobolome alteration and functionality of the female reproductive tract is still lacking. The objective of this study was to explore alterations in estrogen-related signaling and the putative link with endometrial dysbiosis. Methods: Women with infertility and repeated implantation failure (RIF, N = 40) were enrolled in order to explore the putative link between estrogen metabolism and endometrial dysbiosis. Endometrial biopsies were used to measure inflammatory and growth factor molecules. β-glucuronidase enzyme activity and estrogen receptor (ER) expression were also assessed. Results: Herein, increased levels of inflammatory molecules (i.e., IL-1β and HIF-1α) and decreased levels of the growth factor IGF-1 were found in the endometrial biopsies of patients presenting dysbiosis compared to eubiotic ones. β-glucuronidase activity and the expression of ERβ were significantly enhanced in patients in the dysbiosis group. Interestingly, Lactobacilli abundance was inversely related to β-glucuronidase activity and to ERβ expression, thus suggesting that an alteration of the estrogen-activating enzyme may affect the expression of ERs as well. Conclusions. Overall, these preliminary data suggested a link between endometrial dysbiosis and estrobolome impairment as possible synergistic contributing factors to women infertility and RIF.

Simultaneous removal of E1, E2, EE2 and levonorgestrel from water using TiO2 catalyst anchored on activated carbon: Processes optimization, materials characterization, and assessment of the estrogenicity reduction

Removal of estrogen hormones from water matrices is crucial owing to its adverse effects on aquatic ecosystems and human health. The present investigation applies an advanced approach to assess the effectiveness of combined processes (adsorption and visible-light-driven photo-degradation) for simultaneous removal of estrone (E1), 17β-estradiol (E2), 17α-ethinylestradiol (EE2), and levonorgestrel (LEVO) in water, applying TiO2-activated carbon composite selected through design of experiment (DoE) for process optimization. Based on a central composite rotatable design (CCRD), composites were synthesized with percentages of activated carbon (AC) ranging from 2.93% to 17.07% (wt.) and calcination temperatures between 259 and 541 °C. The composite with the best performance TiO2-AC15%-541 (15% wt. AC, calcined at 541 °C), achieved a total removal of 98.3 ± 1.15% for E1, 99.0 ± 1% for E2, 99.3 ± 1.15% for EE2, and 96.0 ± 2.65% for LEVO at the initial concentration of 100 μg L−1 under simulated solar irradiation. Further optimization using once more CCRD involved three independent variables: pH; hormone concentration/TiO2-AC15%-541 loading ratio; and the intensity of simulated solar irradiation. Under optimized conditions (pH 2.64, hormone concentration/TiO2-AC15%-541 loading ratio of 3.8 mg g−1, and irradiation intensity of 41 W m−2 UV-A), the TiO2-AC15%-541 composite removed 99.8% of E1, 99.8% of E2, 99.0% of EE2, and 92.1% of LEVO. Furthermore, the process achieved a 99.9% reduction in estrogenic activity, assessed with yeast estrogen screen (YES) assay. These results demonstrate that TiO2-AC15%-541 is an efficient and cost-effective remediation agent for treating mixed estrogen compounds in water, with significant potential for commercial applications.

Effect of Vaginal Laser and Topical Therapies on Vulvovaginal Atrophy Symptoms in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

Background: Vulvovaginal atrophy (VVA) significantly impacts the quality of life in breast cancer patients leading to symptoms like vaginal dryness, dyspareunia, and genital discomfort. Quality of life in this context is measured using validated scales like the Vaginal Health Index, Visual Analog Scale (VAS), and the Female Sexual Function Index (FSFI). Methods: We performed a systematic review and meta-analysis to identify effective treatment options for VVA, including topical estrogen, systemic hormone therapy, vaginal DHEA, ospemifene, and non-hormonal methods like intravaginal laser therapy, moisturizers, and lubricants. A systematic search of four databases (MEDLINE, Scopus, CENTRAL, Embase) identified studies on VVA treatment efficacy in breast cancer patients, yielding 13,039 records, with 32 eligible studies and 8 included in the meta-analysis. Results: Significant improvements were found with intravaginal laser therapy, showing notable differences in the Vaginal Health Index (MD = 8.24, p < 0.01), dyspareunia (MD = -4.82, p = 0.05), and dryness (MD = -5.05, p = 0.01). However, no significant changes were observed in FSFI and vaginal pH. Notably only intravaginal laser therapy was included in the meta-analysis, as other treatment options lacked comparable data. Both hormonal and non-hormonal treatments improved quality of life, with laser therapy showing the most substantial effects. Conclusions: Intravaginal laser therapy is an effective treatment for VVA symptoms in breast cancer survivors, particularly in improving the Vaginal Health Index and reducing dyspareunia. Despite the strengths of the study, variability among studies, lack of RCT-s and data limitations, especially on long-term effects, present challenges.

Site-specific O-GlcNAcylation of progesterone receptor (PR) supports PR attenuation of interferon stimulated genes (ISGs) and tumor growth in breast cancer

Hormone receptor (HR) positive breast cancer, defined by expression of estrogen (ER) and/or progesterone (PR) receptor expression, is the most commonly diagnosed type of breast cancer. PR alters the transcriptional landscape to support tumor growth in concert with or independent of ER. Thus, understanding the mechanisms regulating PR function are critical to developing new strategies to treat HR+ breast cancer. O-GlcNAc is a post-translational modification responsible for nutrient sensing that modulates protein function. Although PR is heavily post-translationally modified, through phosphorylation and O-GlcNAcylation, specific sites of O-GlcNAcylation on PR and how they regulate PR action, have not been investigated. Using established PR-expressing breast cancer cell lines, we mapped several sites of O-GlcNAcylation on PR. RNA-sequencing after PR O-GlcNAc site mutagenesis revealed site-specific O-GlcNAcylation of PR is critical for ligand-independent suppression of interferon signaling, a regulatory function of PR in breast cancer. Furthermore, O-GlcNAcylation of PR enhances PR-driven tumor growth in vivo. We have delineated one contributing mechanism to PR function in breast cancer that impacts tumor growth, and provided additional insight into the mechanism through which PR attenuates interferon signaling.

Deleterious Biological Effects of Endocrine Disruptors: An Insight into Human Health Risks.

Endocrine-disrupting chemicals (EDCs) are environmental pollutants. Since EDCs are present in various consumer products, contamination of human beings is very common. EDCs have deleterious effects on various systems of the body, especially the endocrine and reproductive systems. EDCs interfere with the synthesis, metabolism, binding, or cellular responses of natural estrogens and alter various pathways. Biological samples such as blood, saliva, milk, placental tissue, and hair are frequently used for biomonitoring and the detection of EDCs. Early detection and intervention may help in preventing congenital anomalies and birth defects. The common methods for determining the presence of EDCs in body fluids include gas chromatography, high-performance liquid chromatography, and mass spectrometry. Understanding the health effects and dangers of EDC is important, given their widespread use. This mini-review aims to summarize the adverse biological effects of several important classes of EDCs and highlights future perspectives for appropriate control.

A multicentre, randomized, double-blind, placebo-controlled trial of topical oestradiol gel for endometrial regeneration after induced abortion.

Is topical oestradiol gel effective in promoting endometrial regeneration after a surgical abortion? Topical oestradiol gel is effective in promoting endometrial regeneration after a surgical abortion with few side-effects. Oestrogen is effective in promoting endometrial regeneration. Transdermal oestrogen has been widely used in clinical practice for endometrial regeneration after induced abortion, but high-level evidence is limited. We conducted a multicentre, superiority, randomized, double-blind, placebo-controlled trial. Between 9 March 2022 and 21 February 2023, 200 women were assigned in a 1:1 ratio to receive either oestradiol gel (treatment) and or oestradiol gel simulant (control) for 28 days. The participants were scheduled to have their endometrial thickness (mm) measured by ultrasonographic scan at 21-23 days post-abortion. The trial was blinded for participants, investigators, medical staff, and statistical analysts until final unblinding. Participants were women undergoing induced abortion within 10 weeks of gestation. A total of 200 participants were enrolled, with 100 in each group. Eighty-eight (88%) in the treatment group and 82 (82%) in the control group completed the study as per the protocol and were included in the per-protocol set (PPS). The intent-to-treat (ITT) analysis included all participants randomized to the study groups and used inverse probability weighting to account for loss to follow-up. The ITT analysis showed revealed significantly greater endometrial thickness in the treatment group (mean 8.1 ± 2.5 mm) compared to the control group (mean 6.9 ± 2.1 mm) 21-23 days postabortion (mean difference 1.2 mm, 95% CI 0.7 to 1.9; P < 0.001). The median time to menstrual return was shorter in the treatment group (34 days, inter-quartile range [IQR] 30-38) than in the control group (35 days, IQR 32-42), with a difference of -1 day (95% CI -2.3 to -0.9; P = 0.036). No differences were observed in the timing or volume of bleeding in the first post-abortion cycle. The PPS analysis mirrored the ITT findings. Adverse events were minimal (6% versus 8%), and the blood profile, liver, kidney and coagulation test results were comparable between groups (all P > 0.05). Loss to follow-up was 11% in the treatment group and 15% of controls, with no significant difference (P > 0.05). Inconsistencies in the timing of the ultrasonographic scans may have affected the accuracy of endometrial thickness measurements. Our findings suggest that topical oestrogen supplementation immediately after abortion within the first 10 weeks of gestation improves endometrial regeneration and growth, thereby potentially increasing the chances of a successful subsequent pregnancy. Clinical application of these findings may improve endometrial health management practices and provide a perspective on fertility treatment and women's reproductive health. This study was supported by a grant (FW-HKKT2021111501900) from Jianmin Pharmaceutical Group Co., Ltd (JMPG), Wuhan, Hubei, China. Both the oestradiol gel and the simulant were provided by JMPG. The funding source had no role in the study. X.Y.L. reports JMPG grant funding paid to their institutions. All other authors declare no competing interests. CHiCTR2100053565. 24 November 2021. 9 March 2022.

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.