Estrogen Production Research Articles

Abstract A32: Exemestane inhibits survival and cell cycle regulators and retards AML cell proliferation

Abstract Acute myeloid leukemia (AML) is the most common type of leukemia with poor prognosis. Although estrogen plays important roles in female cancers, the recent reports indicate that estrogen and its receptors also attribute to the development of non-gender cancers and AML is one of those. Therefore, the inhibition of estrogen production becomes a potential strategy for AML treatment. Exemestane is an aromatase inhibitor and commonly used for reducing estrogen production in breast cancer patients. Our data showed that Exemestane treatment significantly decreased the proliferation of both KG-1 and HL-60 AML cell lines. Since STAT3 and AKT closely collaborate with estrogen receptor in breast cancer cells, their activations are next to be monitored. In KG-1 cells, the phosphorylations of STAT3 (Y705 and S727) and AKT (S473) were both inhibited by Exemestane treatment. Regarding the cell cycle control, p21 was increased by Exemestane in KG-1 cells in which Cyclin E was reduced. It suggests that CDK2 might be inactivated by Exemestane-reduced Cyclin E and therefore p21 escaped from the CDK2-dependent degradation. Although the signaling findings of Exemestane in KG-1 were interesting, no similar results were found in HL-60 cells except the growth inhibition, suggesting the distinct regulation mechanisms between two cell lines. In summary, these results not only suggest, again, the importance of estrogen demand for AML cells, but also show the novel and potential treatment of AML using blockade of estrogen supply, which could be helpful to uncover novel AML treatments in the future. Citation Format: Mei-chih Chen, Pang-Ting Cheng, Yu-Chiao Cheng, Ho Lin, Chieh-Lin Jerry Teng. Exemestane inhibits survival and cell cycle regulators and retards AML cell proliferation [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A32.

A STUDY OF INFLUENCE OF MENOPAUSE ON SERUM LIPID PROFILE

Background: Menopause is a physiological change due to which women passes from fertile to infertile period. Decreased oestrogen production in post menopausal women alter the lipid metabolism. Since altered serum lipid profile seen in menopause is one of the significant risk factors for developing coronary heart diseases, influence of menopause on lipid levels is aimed to study. Aim and Objective: To study the influence of menopause on serum lipid profile by estimating the level of serum cholesterol and various lipoproteins in premenopausal and post menopausal women. Methods: After getting ethical committee approval, in this cross sectional study, women of age 45- 55 and normal BMI attending Government Sivagangai Medical College for master health checkup were selected. Informed consent obtained and estimation of serum lipid profile was done for all of them. Results: Statistical analysis was done by students t test and the results were compared between pre and post menopausal women. In post menopausal women, the mean values of triglycerides (p=0.016) and very low density lipoprotein levels (p=0.046) were increased significantly. Conclusion: Significant increase in serum triglycerides and very low density lipoproteins is due to menopause which causes changes in body metabolism. Serum lipid levels should be checked periodically after menopause and life style modifications should be adviced at an earlier stage.

The novel peptide PFAP1 promotes primordial follicle activation by binding to MCM5.

Premature ovarian failure (POF) is a complication of ovarian dysfunction resulting from the depletion or dysfunction of primordial follicles (PFs) in the ovaries. However, residual follicles that have the potential to be activated are present in POF or aged women. Little is known about the mechanisms by which the remaining dormant PFs in POF patients are activated. Using mass spectrometry, we screened differentially generated peptides extracted from the ovarian cortical tissue biopsies of patients with or without POF, during which we identified PFAP1, a peptide that significantly promoted the activation of PFs in the ovaries of 3 dpp mice in vitro. PFAP1 reversed age-related fertility damage in vivo to a certain extent, promoted estrogen (E2) and anti-mullerian hormone (AMH) production (p < .05), and decreased the levels of follicle-stimulating hormone (FSH) (p < .05). In newborn mouse ovaries, PFAP1 could bind to the protein minichromosome maintenance protein 5 (MCM5) and inhibit its ubiquitination and degradation. In addition, PFAP1 promoted the proliferation of GCs, probably by regulating the function and production of MCM5. In conclusion, PFAP1 could promote the activation of PFs in the ovaries of newborn mice, partially restore the ovarian function of aged mice, and increase the proliferation of primary granulosa cells (GCs) by regulating the function of MCM5. PFAP1 is a promising novel peptide that may be developed into a new therapeutic agent for POF and other ovarian diseases.

Abstract 6465: Associations of early menopause and hormone therapy with lung health and mortality among female never and ever smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract Our previous study using the Lovelace Smokers cohort identified early natural menopause (i.e., age at menopause&amp;lt;45 yr), which is a biomarker of ovarian aging, as a risk factor for lung disease and mortality among female smokers. However, most of the associations reported in female smokers with natural menopause were not observed in those with surgical menopause, (a mixed group of subjects with bilateral oophorectomy or hysterectomy without bilateral oophorectomy). Females with bilateral oophorectomy lose ovarian estrogen and progesterone production, while females with hysterectomy, +/- unilateral oophorectomy, maintain some of this hormone production. We hypothesize that associations between early menopause, lung health and mortality will vary based on type of menopause. Among 69,071 females from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, early menopause rates were 8.7%, 44.1%, and 72.8% in never smokers versus 12.1%, 51.6%, and 78.0% in ever smokers with natural, bilateral oophorectomy, or hysterectomy without bilateral oophorectomy, respectively. We analyzed the associations of early menopause and hormone therapy with lung health (physician diagnosed emphysema and chronic bronchitis and lung cancer incidence) and mortality (all-cause and cause-specific) outcomes by smoking status and menopause types. The most consistent associations were observed for all-cause mortality: 1) Except in never smokers who received hysterectomy only, early menopause was associated with higher all-cause mortality regardless of smoking status 2) hormone therapy was associated with lower all-cause mortality in all groups and the longer the use, the more beneficial the outcome; 3) the magnitude of this association was strongest in those who underwent bilateral oophorectomy. Furthermore, in ethnic disparity analysis, all-cause mortality was affected by early menopause to a lesser degree in non-Hispanic black ever smokers and there was increased benefit from hormone therapy in non-Hispanic black never smokers. Overall, we identified further evidence supporting early menopause as a risk factor for lung health and mortality and hormone therapy as being beneficial regardless of smoking status or menopause type. Our results support the “shorter lifetime estrogen exposure in early menopause” hypothesis and the clinical importance of hormone therapy beyond withdrawal symptom coping. Supported by National Cancer Institute (NCI) grant P30 CA118100. The authors thank the NCI for access to NCI's data collected by the PLCO Cancer Screening Trial (the Cancer Data Access System Project Number PLCO-981). Citation Format: Tessa Flores, Xiaochun Gai, Yiliang Zhu, Kimberly Leslie, Shuguang Leng. Associations of early menopause and hormone therapy with lung health and mortality among female never and ever smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6465.

The correlation between clinical biochemical parameters and bone mineral density in postmenopausal women

&lt;b&gt;Objective:&lt;/b&gt; Menopause is characterized by the end of reproductive ability in the female life cycle, and which is the permanent cessation of menstruation. After menopause, the ovaries cut off the production of estrogen, after which important symptoms and diseases occur for women’s health due to estrogen deficiency. The aim of this study is to investigate the clinical, hormonal and biochemical parameters on bone mineral density (BMD) in postmenopausal women.&lt;br /&gt; &lt;b&gt;Method: &lt;/b&gt;535 postmenopausal women were included in the study. Demographical parameters, biochemical, and hormonal serum levels were investigated. These values were statistically analyzed with Pearson correlation test with BMD values.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; Significantly positive correlation is detected between patient’s height and lumbar T score (LtotT), lumbar Z score (LtotZ), and femoral T score (FtotT) (p=0.00, p=0.001, and p=0.00). Positive correlation was detected between patient’s weight and body mass index, and LtotT, LtotZ, FtotT, and femoral Z score (FtotZ) scores (p=0.00). Significantly negative correlation was detected between patient’s aspartate transaminase (AST) values and FtotT and FtotZ scores (p=0.002, p=0.004). Positive correlation was detected between patient’s phosphate (P) values, and FtotT and FtotZ scores (p=0.012, p=0.030). Negative correlation was detected between patient’s magnesium (Mg) values, and LtotT and LtotZ scores (p=0.016, p=0.032).&lt;br /&gt; &lt;b&gt;Conclusions:&lt;/b&gt; BMD values are positively related with height, weight, serum phosphate levels, and negatively related with serum AST and Mg levels in postmenopausal women.

MP15-17 IMPACT OF VAGINAL PRASTERONE ON THE RATE OF URINARY TRACT INFECTIONS IN GSM PATIENTS AND THOSE WITH A HISTORY OF BREAST CANCER: A RETROSPECTIVE COHORT ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP15-17 IMPACT OF VAGINAL PRASTERONE ON THE RATE OF URINARY TRACT INFECTIONS IN GSM PATIENTS AND THOSE WITH A HISTORY OF BREAST CANCER: A RETROSPECTIVE COHORT ANALYSIS Rachel Rubin, Erick Moyneur, Katherine Dea, Fernand Labrie, and Alain Dury Rachel RubinRachel Rubin More articles by this author , Erick MoyneurErick Moyneur More articles by this author , Katherine DeaKatherine Dea More articles by this author , Fernand LabrieFernand Labrie More articles by this author , and Alain DuryAlain Dury More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003235.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Genitourinary Syndrome of Menopause (GSM) is attributed to a decline in the levels of circulating sexual steroids which often results in increased vaginal pH, atrophic urogenital changes, elevated amount of post-void residual urine, and changes in the vaginal microbiome with a shift towards a predominance of fecal gram-negative bacteria rather than lactobacilli, which is believed to create a potential reservoir for recurrent urinary tract infections (UTIs). Current guidelines to prevent recurrent UTIs include vaginal estrogens. Intravaginal prasterone is converted locally in the vaginal tissue into androgens which are subsequently aromatised into estrogens. It is indicated to treat moderate to severe dyspareunia in postmenopausal women in the US. The objective of this study was to assess, through real world evidence data, the potential of vaginal prasterone to be used in postmenopausal GSM women with recurrent UTIs as prophylaxis to reduce the future UTI risk. As a sensitivity analysis, women using aromatase inhibitors, medications that stop the production of estrogen in postmenopausal women typically prescribed to women with a history of breast cancer, were analyzed. METHODS: This retrospective matched-cohort study was conducted using the Integrated Dataverse (IDV®) - an open-source claims database from Symphony Health Solutions with data from February 2015 through January 2020. RESULTS: 22,245 women treated with prasterone for a minimum of 12 weeks were matched to women without any prescribed VVA-related treatment. Within each of these two groups, 286 matched patients were taking aromatase inhibitors. Across all age groups, women treated with prasterone have a significantly lower UTI prevalence compared to those untreated (6.58% and 12.3%, respectively; p˂0.0001). The highest difference in UTI prevalence among the prasterone treated and untreated women was observed in those aged 65-74 (7.15% and 16.2% respectively; p˂0.0001). Consistent with the above, among aromatase inhibitor users, women treated with prasterone have a significantly lower UTI prevalence (4.90% vs. 9.79%; p=0.008). CONCLUSIONS: This study suggests that intravaginal prasterone may be a good candidate for prophylaxis in postmenopausal women with recurrent UTIs to reduce future UTI risk, including for patients taking aromatase inhibitors and having contraindications for estrogen-based therapies. This study is however based on real-world evidence and warrants further investigation in a clinical setting. Source of Funding: Endoceutics © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e199 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rachel Rubin More articles by this author Erick Moyneur More articles by this author Katherine Dea More articles by this author Fernand Labrie More articles by this author Alain Dury More articles by this author Expand All Advertisement PDF downloadLoading ...

Pubertal induction in Turner syndrome without gonadal function: A possibility of earlier, lower-dose estrogen therapy.

Delayed and absent puberty and infertility in Turner syndrome (TS) are caused by primary hypogonadism. A majority of patients with TS who are followed at hospitals during childhood will not experience regular menstruation. In fact, almost all patients with TS need estrogen replacement therapy (ERT) before they are young adults. ERT in TS is administered empirically. However, some practical issues concerning puberty induction in TS require clarification, such as how early to start ERT. The present monograph aims to review current pubertal induction therapies for TS without endogenous estrogen production and suggests a new therapeutic approach using a transdermal estradiol patch that mimics incremental increases in circulating, physiological estradiol. Although evidence supporting this approach is still scarce, pubertal induction with earlier, lower-dose estrogen therapy more closely approximates endogenous estradiol secretion.

Tingkat Kecemasan Remaja Wanita Terhadap Siklus Menstruasi Selama Pandemi Covid-19 Di SMAN 1 Maluku Tenggara

Increased anxiety in adolescent girls causes the production of estrogen, progesterone and various other hormones in the body to become unstable. causing irregular menstrual cycles. Caused the effect of stress by the changes in life during the Covid-19 pandemic. The purpose of this study was to determine the effect of female adolescent anxiety levels on the menstrual cycle during the Covid-19 pandemic at Public High School 1 Maluku Tenggara. The design of this research is observational analytic with a cross sectional approach. Respondents were taken by simple random sampling technique. The population is 175 with a sample of 64 people. The results of statistical tests using logistic regression. The results of data analysis show that the significance level is 0.001 &lt; = 0.05 so that H0 is rejected and H1 is accepted, thus there is an Influence of Adolescent Girls' Anxiety Levels on Menstrual Cycle During the Covid-19 Pandemic Period at Public High School 1 Maluku Tenggara. It is recommended for young women who experience anxiety to convey their complaints and problems to counseling teachers at schools and health workers so that they can help overcome their problems and reduce their anxiety.

Preparation of pumpkin oil-based nanoemulsion as a potential estrogen replacement therapy to alleviate neural-immune interactions in an experimental postmenopausal model

As estrogen production decreases during menopause; the brain's metabolism tends to stall and become less effective. Estrogen most likely protects against neurodegeneration. Consequently, a comprehensive study of the benefits of hormone replacement therapy as a neuroprotective effect is urgently required. This study was designed to fabricate pumpkin seed oil nanoparticles (PSO) in nanoemulsion form (PSO-NE) and investigate their potential role in attenuating the neural-immune interactions in an experimental postmenopausal model.Sixty female white albino rats were divided into six groups: control, sham, ovariectomized (OVX), and three OVX groups treated with 17β-estradiol, PSO, and PSO-NE respectively. Transmission Electron Microscopy (TEM), and particle size analyzer were performed for nanoemulsion evaluation. Serum levels of estrogen, brain amyloid precursor protein (APP), serum levels of nuclear factor kappa B (NF-κβ), interleukin 6 (IL-6), transthyretin (TTR), and synaptophysin (SYP) were evaluated. The expression of estrogen receptors (ER-α, β) in the brain tissue was estimated. The findings revealed that the approached PSO-NE system was able to reduce the interfacial tension, enhance the dispersion entropy, lower the system free energy to an extremely small value, and augment the interfacial area. PSO-NE, showed a significant increase in the levels of estrogen, brain APP, SYP, and TTR accompanied with a significant increased in the expression of brain ER-α, β compared to the OVX group. In conclusion, the phytoestrogen content of PSO exhibited a significant prophylactic effect on neuro-inflammatory interactions, ameliorating both estrogen levels and the inflammatory cascades.

Long-Term Exposure to Isoflavones Alters the Hormonal Steroid Homeostasis-Impairing Reproductive Function in Adult Male Wistar Rats

The consumption of isoflavones is gaining popularity worldwide due to their beneficial effects on health. However, isoflavones are considered to be endocrine disruptors and cause deleterious effects on hormone-sensitive organs, especially in males. Therefore, this study aimed to determine if a continuous and prolonged exposure to isoflavones in adult males altered the endocrine axis effect of testicular function. For this purpose, seventy-five adult male rats were administered with low and high mixtures of isoflavones (genistein and daidzein) for 5 months. The determination of steroid hormones (progesterone, androstenedione, dehydroepiandrosterone, testosterone, dihydrotestosterone, 17β-estradiol, and estrone sulphate) was carried out in serum and testicular homogenate samples. Sperm quality parameters and testicular histology were also determined. The results revealed that low and high doses of isoflavones promote a hormonal imbalance in androgen and estrogen production, resulting in a decrease in circulating and testicular androgen levels and an increase in estrogen levels. These results are associated with a reduction in the sperm quality parameters and a reduction in the testicular weight, both in the diameter of the seminiferous tubules and the height of the germinal epithelium. Altogether, these results suggest that a continuous exposure to isoflavones in adult male rats causes a hormonal imbalance in the testes that disrupts the endocrine axis, causing defects in testicular function.

Abstract P6-12-02: Connecting Fluctuations in Estrogen Production, Release, and Action with Hormone-Dependent Gene Expression in Breast Cancers

Abstract Estrogens are steroid hormones that play a key role in a wide range of physiological and pathological processes. Estrogen receptor-alpha, ERɑ, functions primarily as a nuclear transcription factor (TF) through ligand-dependent activation by 17β-estradiol (E2), the predominant naturally-occurring estrogen. This results in dimerization, DNA binding to cis-regulatory elements called enhancers, and gene regulatory function of ERɑ. In vivo, E2 production and action fluctuates during reproductive cycles and possibly even in a circadian manner. In tissues and cells, E2-regulated gene expression is dynamic, with rapid induction of enhancer formation and target gene expression (or repression), followed by enhancer “decommissioning” and cessation of the gene regulatory effects. The effects of sustained E2 production and signaling, fluctuations in E2 levels, and removal of E2 on estrogen-regulated gene expression are unknown. Classical experiments exploring the gene regulatory effects of E2 involve stimulation of cultured cells throughout the duration of the experiment with a continuous and typically high dose of hormone, with the cells harvested at the end of the stimulation period. While this has allowed us to understand the molecular underpinnings of signal-dependent transcription, it has not allowed analysis of physiological fluctuations in estrogen signaling involving periods of stimulation (i.e., the presence of hormone) and non-stimulation (i.e., the absence of hormone). In our studies, we are applying a combination of next generation sequencing techniques and fluorescence microscopy to investigate signal-dependent responses to fluctuating and short duration E2 exposures using ERɑ-positive MCF-7 human breast cancer cells after E2 treatment and removal. Our initial results suggest that different E2 target genes respond differently to low dose E2 treatment and E2 withdrawal. Moreover, for some E2 target genes, sustained E2 treatment may not be required for a complete E2 transcriptional response. With these studies, we hope to connect physiological aspects of E2 production, release, and action with the molecular mechanisms of E2-dependent gene expression - an aspect of our understanding of estrogen signaling that has been lacking. Citation Format: Hyung Bum Kim, William L. Kraus. Connecting Fluctuations in Estrogen Production, Release, and Action with Hormone-Dependent Gene Expression in Breast Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-12-02.

Abstract P2-26-17: Establishment of an in vitro preclinical platform: A living biobank of patient-derived organoids with ER+ breast cancer

Abstract Introduction and objectives Estrogen receptor positive (ER+) tumors are the most common form of breast cancer and are responsible for most of the deaths from the disease. Treatment of ER+ breast cancer comprises interventions that suppress estrogen production and/or target the ER directly. While endocrine therapy has considerably reduced recurrence and mortality from breast cancer, de novo and acquired resistance to this treatment remains a major challenge. In this context, patient-derived organoids (PDOs), 3D structures composed of epithelial cells, are changing our understanding of cancer heterogeneity and its implications for personalized medicine. Our aim was to establish and characterize a PDO platform of ER+ breast cancer as preclinical tool to decipher and target this heterogeneity in order to tailor effective treatments based on the precise molecular makeup of the tumor. Material and Methods Surgical resections were collected from patients diagnosed with ER+ breast cancer. Organoid generation from patient material were divided in three main steps: 1) mechanical fragmentation of tissue pieces; 2) digestion of fragments into single-cell suspension; and 3) plating of cell preparations into matrigel domes to mimic the extracellular matrix. Organoids were passaged every 7–21 days based on confluency. Each newly organoid line was cryopreserved for further expansion. Results We have successfully achieved an outgrowth efficiency of almost 50% for PDOs from patients diagnosed with breast cancer. Characterization of PDO cultures is essential to validate its predictive potential. To asses that PDOs represent the tumor of the patient, for each organoid line, expression levels of the main histological markers (ER, PR, HER2, Ki67) were evaluated and correlated with the tissue of origin. In parallel, we have performed immunofluorescence on paraffin-embedded organoid samples with routinely used cancer stem cell markers. Potential contamination with normal cells (present in the resection used to establish the culture) should be considered. To address the tumor purity of the culture we have performed targeted DNA sequencing in both the original tissue and established PDOs. Conclusions PDOs represent a superior preclinical system compared to previous models due to their inherent heterogeneity, long-term stability, applicability for high-throughput screens and enhanced capacity to capture tumor characteristics. Therefore, the implementation of a well-annotated patient-derived organoid biobank will be of great interest for drug discovery and personalized therapy. Understanding the sources and implications of tumor heterogeneity will undoubtedly improve our evolving definition of cancer and aid in the design of effective patient-specific treatment strategies. Citation Format: Maria A Dominguez-Cejudo, Raquel Chapresto, Ana Gil-Torralvo, Francisco Javier Salvador Bofill, Sonia Molina-Pinelo. Establishment of an in vitro preclinical platform: A living biobank of patient-derived organoids with ER+ breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-17.

Conjugate treatment with high concentration normobaric oxygen and hyaluronic acid for vaginal atrophy: a prospective study.

Vulvovaginal atrophy is a condition closely related to low circulating estrogen levels, with post-menopause being the main cause. However, patients of childbearing age may also present with these symptoms due to treatments that reduce estrogen production. Local estrogen therapy is the causal treatment of local symptoms, but it is not always accepted and is often abandoned by patients. In recent years, alternative therapies have been proposed: fractional CO2 laser or the conjugate treatment with normobaric oxygen and hyaluronic acid, the latter being the subject of this study. The study aimed to evaluate the effectiveness of conjugate topical treatment with normobaric oxygen and hyaluronic acid. 50 patients were evaluated and treated with 5 applications of 15 minutes each, every 15 days, with Caressflow®. All patients presented at least one of the symptoms related to vulvovaginal atrophy: dryness, burning, and dyspareunia. In all cases, vulvoscopy, colposcopy, and cervicovaginal cytology were performed. The patients were interviewed with an analogic scale (VAS) concerning the severity of symptoms before and after the treatment. Colposcopy and PAP-smear were assessed by mean of Vaginal Health Index Score (VHI) at baseline and at the end of the treatment. All patients completed the treatment scheme and presented with a significant improvement in subjective symptoms. The colposcopy and PAP-smear performed 10 days after the end of the last treatment showed a significant improvement in the appearance and elasticity of the vaginal epithelium and the cytological picture, which showed, in the sample taken after treatment, hyaluronic acid vesicles within the cell cytoplasm. This study corroborates the data presented in the latest published papers on the effectiveness of treatment with normobaric O2 and hyaluronic acid on vaginal atrophy. Efficacy has been confirmed both in terms of subjective symptoms reported by the patients and objective improvement at colposcopy and PAP-smear cytology.

Implications of Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer

Aromatase Inhibitor(AI) therapy is a crucial treatment for regulating estrogen production that combats breast cancer in postmenopausal patients. Clinical trials have emphasized its importance, as it has surpassed its prior efficacy through each succeeding generation of AI therapy and surpassed other treatment options like estrogen modulators(Tamoxifen) and Progestin therapy(Megace/Megestrol Acetate). There is a big difference between AI therapy and other therapies, though they all ultimately attempt to stop the proliferation of cancerous cells. AI therapy has been shown to be effective; however, some side effects of its use have been challenging its place in recent studies. Many physicians have noticed and questioned its use, and future research addressing these concerns needs to be executed in order to enhance the quality of life for our breast cancer patients. In this paper, an overview of the current status of breast cancer, the details of breast cancer and its development, the different types of breast cancer, the workings of AI therapy, clinical trials of Aromatase Inhibitor therapy, a comparison of different therapies, Physician input, and future implications of its effectiveness will be discussed in detail.

Gene Expression and Epigenetic Modification of Aromatase during Sex Reversal and Gonadal Development in Blotched Snakehead (Channa maculata)

The cyp19a1 gene codes aromatase that converts androgen to estrogen, which plays a central role in early female differentiation and ovarian development in teleosts. For the blotched snakehead (Channa maculata), an important aquaculture fish that is susceptible to hormone-induced sex reversal, two aromatase genes were characterized in the present study, cyp19a1a and cyp19a1b. We analyzed gene expression and the epigenetic state of cyp19a1a and cyp19a1b in different adult tissues: the gonad and brain from normal XX females (XX-F), normal XY males (XY-M), sex-reversal females (XY-F) induced by estrogen, and YY super-males (YY-M), and gonads at different development stages. Cyp19a1a exhibited strong female-biased expression patterns in the ovary, and cyp19a1b dominantly expressed in the brain with no sex bias. Cyp19a1a’s expression pattern in the XY-F ovary was similar to that in the XX-F ovary, with a relatively high expression level, which was far higher than that in XY-M and YY-M testis. Meanwhile, CpG methylation levels of cyp19a1a promoter were lower in XX-F and XY-F ovaries compared with XY-M and YY-M testis. A significantly negative correlation between the CpG methylation levels and cyp19a1a expression was elucidated in XX-F, XY-M, XY-F, and YY-M gonads. Furthermore, the strong female-biased cyp19a1a expression was closely related to ovarian differentiation and maturation, and the overall methylation levels of cyp19a1a promoter were inversely correlated with cyp19a1a expression. There were no detectable sexually dimorphic differences in cyp19a1b expression and CpG methylation levels of cyp19a1b promoter in the brain and gonad between sexes in C. maculata, thus the function of cyp19a1b in C. maculata needs further research. Our research illustrates that cyp19a1a is closely related to estrogen production, ovary differentiation/maintenance, and sex reversal, and epigenetic modification plays a crucial part in maintaining the sexual dimorphic expression of cyp19a1a, ovarian differentiation and oogenesis in C. maculata.

The Effectiveness of Education on Mothers' Anxiety Levels in Facing Menopause

 Elderly is someone who has reached the age of 60 (sixty) years and over. The world's elderly population (age 60 years and over) is growing very fast, even the fastest when compared to other age groups. Menopause is a condition in a woman who experiences a decrease in ovarian function which results in a decrease in the production of the hormone estrogen. This situation, among other things, will result in the cessation of menstruation forever. The purpose of this study was to determine the effectiveness of education on the level of maternal anxiety in facing menopause. The design of this study is analytic with this is a pre-experiment with the One Group Pre-post Test design. By using a cohort approach. Population using total sampling. The population in this study were all mothers who lived in the Cempokolimo elderly hut, Pacet District, Mojokerto Regency. A sample of 31 respondents was obtained in November 2022. Data was collected by means of a questionnaire using the HARS scale with 14 questions and modified according to the emergence of changes, signs and symptoms that can cause anxiety in menopausal women. The statistical test used was the Wilcoxon signed rank test. The results showed that most of the anxiety levels before being given education (pre test) were mild anxiety, namely 18 people (58.1%), not anxious 3 people (9.7%), moderate anxiety 8 people (25.8 %) and severe anxiety in 2 people (6.4%). Results Most of the anxiety levels after being given education (post test) were not anxious, namely 18 people (58.1%), mild anxiety 10 people (32.2%) and moderate anxiety 3 people (9.7%) ). Statistical Test Results Based on the results of the Wilcoxon Signed Rank Test it shows that the significance value is 0.000 &lt;α (0.05). Because the significance value is &lt; α (0.05), then H0 is rejected, which means that there is an influence on the effectiveness of education on the level of anxiety of mothers in facing menopause. the changes that are going through. Seeing the results of this study, there is still a need for regular health education education to reduce mothers' anxiety in dealing with menopausal changes

Non-hormonal treatments of menopausal symptoms

Menopause is a natural ageing process that affects all women. It is caused by the gradual reduction in ovarian follicular function, leading to a reduction in oestrogen production. Menopause can have a variety of direct symptomatic effects – with many women affected by vasomotor (hot flushes and sweats), cardiovascular, musculoskeletal, urogenital and psychological symptoms. It is important to recognise that despite it being a natural process, menopausal symptoms can significantly affect quality of life, often co-existing with career or caring responsibilities, for example, senior roles at work or teenage children and ageing parents. The goal of this review is to aid clinicians in providing care for patients with these problems and unable to, or choosing not to, undergo hormone replacement therapy.

Co-cultivation of human granulosa cells with ovarian cancer cells leads to a significant increase in progesterone production

PurposeIn humans, granulosa cells (GCs) are part of the follicle and nourish the growing oocyte. GCs produce estrogen and, after ovulation, progesterone. They are embedded in a multicellular tissue structure of the ovary, which consists of a variety of different cell types that are essential for the physiological function of the ovary. However, the extent to which individual ovarian cell types contribute to overall functionality has not yet been fully elucidated. In this study, we aim to investigate the effects of co-culturing human granulosa cells with ovarian cancer cells on their progesterone and estrogen production in an in vitro model.MethodsAfter seeding, the cells were stimulated with 200 µM forskolin in DMEM for 72 h and the medium of the different cell culture experiments was collected. Subsequently, progesterone and oestradiol concentrations were determined using an Elisa assay.ResultsMorphologically, it was striking that the cells self-organize and form spatially separated areas. Compared to culturing granulosa cells alone, co-culturing human granulosa cells together with the ovarian cancer cell line OvCar-3 resulted in a significant increase in progesterone production (20.3 ng/ml versus 50.2 ng/ml; p < 0.01).ConclusionsUsing a simple in vitro model, we highlight the importance of cellular crosstalk between different ovarian cells in a complex cellular network and that it strongly influences granulosa cell hormone production. This could have potential implications for the procedure of transplanting endocrine tissues after cryopreservation, as it highlights the importance of survival of all cells for the functionality of the transplanted tissue.

E2/ER signaling mediates the meiotic arrest of goat intrafollicular oocytes induced by follicle-stimulating hormone

Abstract The increased production of high-quality oocytes lies at the heart of the search to accelerate the reproduction of high-quality breeding livestock using assisted reproductive technology. Follicle-stimulating hormone (FSH) maintains the arrest of oocyte meiosis during early follicular development in vivo and promotes the synchronous maturation of nucleus and cytoplasm to improve oocyte quality. However, the mechanism by which FSH maintains meiotic arrest in oocytes is still not fully understood. Oocytes spontaneously resume meiosis once released from the arrested state. In this study, we isolated goat antral follicles with a diameter of 2.0–4.0 mm, cultured them in vitro either with or without added FSH, and finally collected the oocytes to observe their meiotic state. The results showed that FSH effectively inhibited the meiotic recovery of oocytes in follicles [4 h: control (n = 84) vs. with FSH (n = 86), P = .0115; 6 h: control (n = 86) vs. FSH (n = 85), P = 0.0308; and 8 h: control (n = 95) vs. FSH (n = 101), P = 0.0039]. FSH significantly inhibited the downregulation of natriuretic peptide receptor 2 (NPR2) expression and cyclic guanosine monophosphate (cGMP) synthesis during follicular culture in vitro (P &amp;lt; 0.05). Further exploration found that FSH promoted the synthesis of 17β-estradiol (E2) (P = .0249 at 4 h and P = .0039 at 8 h) and maintained the expression of the estrogen nuclear receptor ERβ, but not the estrogen nuclear receptor ERα during follicle culture in vitro (P = .0190 at 2 h, and P = .0100 at 4 h). In addition, E2/ER (estrogen nuclear receptors ERα and ERβ) mediated the inhibitory effect of FSH on the downregulation of NPR2 expression and cGMP synthesis, ultimately preventing the meiotic recovery of oocytes (P &amp;lt; .05). In summary, our study showed that FSH-induced estrogen production in goat follicles, and the E2/ER signaling pathway, both mediated meiotic arrest in FSH-induced goat oocytes.

The Comparative Study of the Administration of the Combination Preparation of Isoflavones and Hyaluronic Acid in Menopausal Women for the Treatment of the Symptoms of Menopause, Urogenital Atrophy and Oteoporosis in Relation to Existing Hormone Replacement Therapies.

Menopause is characterized by a series of symptoms and effects from the various systems and organs, for which, the decline in estrogen production from the ovaries is considered responsible. The aim of this study was to make comparative study of the administration of the combination preparation of isoflavones and hyaluronic acid in menopausal women for the treatment of the symptoms of menopause, urogenital atrophy and osteoporosis in relation to existing hormone replacement therapies. In this five-year, double-blind, placebo-controlled clinical study, a total of 274 postmenopausal women were enrolled and classified into three groups. Participants in group A, were 96 women who did not receive Hormone Replacement Therapy (HRT), in the second group, 92 received daily treatment with tibolone (2.5 mg) as monotherapy, and in the third group, 86 received treatment with a pharmaceutical formulation of hyaluronic acid 120 mg and isoflavones. MF11RCE 80 mg. In the postmenopausal women of our study, a significant reduction of postmenopausal symptoms was found in both groups B and C of participants who received hormone replacement preparations compared to group A who did not receive HRT. Furthermore, no difference in efficacy was observed between the administered preparations of isoflavones and tibolone. The combination of isoflavones and hyaluronic acid has the same efficacy as tibolone in menopausal symptoms.