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Objective: Polycystic ovary syndrome (PCOS) is widely reported among young females, and anti-androgens are used for treating hirsutism and acne in these patients. The protective effects of myo-inositol, oral contraceptives, and insulin sensitizers have been reported on the periodontium and high-sensitivity C-reactive protein (hsCRP) levels in PCOS females. However, cyproterone acetate/ethinyl estradiol (CPA/EE) has not yet been studied. This cross-sectional study explores the periodontal status and systemic inflammation in PCOS women on CPA/EE drug combination compared to females not on medication. Method and materials: A total of 150 participants were enrolled into three groups: 50 newly diagnosed PCOS females not on medication (N-PCOS); 50 PCOS females consuming CPA/EE combination for the last 6 months (PCOS+CPA/EE); and 50 systemically healthy females (control group). Anthropometric, biochemical, periodontal parameters, and health-related quality of life questionnaires were recorded. Results: N-PCOS and PCOS+CPA/EE groups showed a nonsignificant difference in hsCRP levels, Gingival Index, bleeding on probing, waist circumference, and waist-hip ratio (P > .05). Gingival thickness and keratinized tissue width were significantly greater in the PCOS+CPA/EE than the N-PCOS group (P = .05); however, these were comparable with the control group (P > .05). Regression analysis showed significant association of bleeding on probing with Gingival Index, clinical attachment level, and hsCRP (P = .05). Conclusions: CPA/EE combination does not influence the periodontal and systemic inflammatory status in PCOS females, as similar levels of local and systemic inflammation were observed in CPA/EE consumers compared with PCOS females not on medication. However, it might play a role in increasing gingival thickness and keratinized tissue width in these patients. [ABSTRACT FROM AUTHOR]

PURPOSE: Treatment guidelines for gender-affirming hormone therapy with estrogen (GAHT-E) recommend specific dosing regimens based on limited data. Well-controlled efficacy trials are essential to tailoring treatment to patient goals as the guidelines recommend. The goal of this study was to take a foundational step toward designing community-centered effectiveness trials for gender-diverse individuals seeking GAHT-E. METHODS: Our team developed a cross-sectional survey based on broad clinical experience and consultation with our community advisory board. The survey included 60 items covering demographics, transition history, goals and priorities for treatment, indicators of treatment success, sexual function goals, and future research priorities. The survey was distributed during the summer of 2021, primarily through social networks designed for gender-expansive individuals seeking treatment with estrogen. RESULTS: A total of 1270 individuals completed the survey. Overall treatment goals most frequently rated extremely important or very important were the following: (1) improved satisfaction with life (81%), (2) appearing more feminine (80%), (3) appearing less masculine (77%), (4) improved mental health (76%), and (5) being seen as your true gender by others (75%). The three body characteristics most frequently rated highest priority or high priority among changes were the following: (1) facial hair (85%), (2) breast shape or size (84%), and (3) body shape (80%). The highest-rated research priority was comparing feminization with different routes of estrogen administration. CONCLUSION: The goals and experiences of individuals seeking GAHT-E are diverse. Future clinical trials of GAHT-E should be grounded in the needs and priorities of community stakeholders.

Delayed puberty is defined as the lack of development of secondary sex characteristics in childhood. Based on a review of the literature, delayed puberty can be divided into three main categories: (i) hypergonadotropic hypogonadism (congenital and acquired); (ii) permanent hypogonadotropic hypogonadism (congenital and acquired); and (iii) transient hypogonadotropic hypogonadism [constitutional delay of growth and puberty (CDGP) and functional hypogonadotropic hypogonadism]. CDGP is the most common cause of hypogonadism in both males and females, accounting for 60% and 30% respectively. Testosterone is the primary treatment for male hypogonadism, while estrogen and progesterone are used for female hypogonadism. However, in recent years, physiological induction therapy protocols such as human chorionic gonadotropin (hCG) monotherapy, hCG + follicle-stimulating hormone combined therapy, and gonadotropinreleasing hormone infusion have been recommended for the treatment of hypogonadotropic hypogonadism to increase long-term fertility success. There is no clear consensus on treatment protocols for physiological induction treatment and its effect on fertility. This review will discuss the clinical approach to hypogonadism, as well as traditional and physiological induction protocols. [ABSTRACT FROM AUTHOR]

Background Breast cancer consists of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated. Methods We conducted a qualitative, scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis, extension for Scoping Reviews to investigate consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER-defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White. We reviewed publications between January 1, 1990 and July 1, 2022. Etiologic heterogeneity evidence (convincing, suggestive, none, or inconclusive) was determined by expert consensus. Results Publications per risk factor ranged from 14 (benign breast disease history) to 66 (parity). Publications were most abundant for White women, followed by Asian, Black or African American, and Hispanic or Latina women. Etiologic heterogeneity evidence was strongest for parity, followed by age at first birth, postmenopausal body mass index, oral contraceptive use, and estrogen-only and combined menopausal hormone therapy. Evidence was limited for other risk factors. Findings were consistent across racial and ethnic groups, although the strength of evidence varied. Conclusion The literature supports etiologic heterogeneity by ER for some established risk factors that are consistent across race and ethnicity groups. However, in non-White populations evidence is limited. Larger, more comparable data in diverse populations are needed to better characterize breast cancer etiologic heterogeneity. [ABSTRACT FROM AUTHOR]

Background: In recent years, antibiotic resistance rates have become a global concern for clinicians to combat the pathogenic bacteria associated with UTIs. The objective of this current paper is to explore the evidence-based use of natural products as an alternative strategy to reduce the recurrence rates among different UTI patient populations such as pregnant women, postmenopause women, and children. Main body: Commonly used non-antimicrobial products to treat and prevent UTIs include vaginal estrogen, cranberry, probiotics, D-mannose, hyaluronic acid (HA), Chinese herbal medicine, and ascorbic acid. Literature supports the safety and effectiveness of utilizing these products in different UTI patients to a great extent. The strongest recommendation was given to the utilization of vaginal estrogen replacement therapy in postmenopausal females to prevent rUTI. Conclusion: We believe our research is the first to provide evidence-based clinical practice guidelines and insight into UTI management using non-antimicrobial drugs in different populations. Our findings can guide future research on the reduction of antimicrobial misuse and preventing antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Introduction: The endometrium plays a crucial role in early human pregnancy, particularly in embryo implantation, survival, and growth. However, invasion and infection by pathogens can lead to endometritis, infertility, and poor reproductive outcomes. Understanding the mechanisms of endometritis and its impact on fertility remains limited. An infection model using patient-derived endometrial epithelial gland organoids (EEGOs) was established to advance in vitro studies on endometritis and related infertility. Methods: An EEGOs infection model was constructed and characterized from human endometrium, treating the organoids with estrogen and progesterone to observe changes in the proliferative and secretory phases. The organoids were infected with E. coli , and the release of inflammatory cytokines in the supernatant was detected using ELISA. RNA-seq was employed to analyze the differences before and after E. coli treatment, and differential gene mRNA expression was validated using real-time quantitative PCR. Additionally, the effect of E2 in alleviating inflammation was assessed through markers of receptivity (PAEP, LIF, ITGβ), proliferation (Ki67), and barrier repair (ZO-1). Results: The constructed human EEGOs exhibited long-term expansion capability, genetic stability, and characteristic hormonal responses, strongly expressing epithelial markers (MUC1, E-Cadherin). After E. coli infection, the expression levels of inflammatory cytokines TNF-α, IL-8, and IFN-γ increased significantly (P < 0.05). RNA-seq indicated that the MAPK signaling pathway was activated post-infection, with increased expression levels of heat shock proteins and transcription factor mRNA. E2 treatment post-infection significantly decreased the mRNA expression of inflammatory genes IL-1β, IL8, IL6 and TNF-α compared to the E. coli infected group (P < 0.05). Additionally, the expression of genes related to receptivity, proliferation, and barrier repair was enhanced in the E2-treated organoids. Conclusions: Our findings demonstrate that patient-derived EEGOs are responsive to bacterial infection and are effective models for studying host-pathogen interactions in bacterial infections. These organoids revealed the anti-inflammatory potential of E2 in alleviating E. coli -induced inflammation, providing insights into the mechanisms of endometritis and its impact on infertility. The study supports the use of EEGOs as valuable tools for understanding endometrial health and developing targeted treatments. [ABSTRACT FROM AUTHOR]

Metaflammation is low-grade inflammation triggered by chronic metabolic imbalance and caused by dysregulated metabolites in metabolic inflammatory syndrome (MIS), which includes four diseases: obesity, type 2 diabetes mellitus (T2DM), atherosclerosis (AS), and nonalcoholic fatty liver diseases (NAFLD, recently proposed to be replaced by metabolic dysfunction-associated steatotic liver disease, MASLD). These diseases exhibit apparent sex dimorphism as regards MIS. Estrogen not only plays a crucial role in gender differences in adults but also possesses an anti-inflammatory effect on many metabolic diseases. In this study, we present a prediction of the differential proteins and signal transduction of estrogen in MIS through network pharmacology and review the validated studies on obesity, T2DM, AS, and NAFLD. Subsequently, we compared them to obtain valuable targets, identify current gaps, and provide perspectives for future research on the mechanisms of estrogen in metaflammation. [ABSTRACT FROM AUTHOR]

Background: This study employed a bidirectional Mendelian Randomization (MR) approach to explore the causal relationships between Oral Lichen Planus (OLP), diabetes mellitus (DM), and glycemic control. It also aims to identify potential pharmacological and herbal treatments that effectively address both OLP and the metabolic dysfunctions associated with DM. Methods: This study employs a two-way MR approach to investigate the potential causal relationships between diabetes type and glycated hemoglobin (HbA1c) levels, and the risk of OLP. We analyzed differentially expressed genes from the OLP dataset in the Genomics Expression Omnibus (GEO) database, cross-referencing these with HbA1c-related genes for enrichment analysis. Additionally, the Drug-Gene Interaction Database (DGIdb) and Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to assess the effectiveness of specific drugs, herbs, and ingredients in treating OLP while managing blood glucose levels. Results: The MR analysis revealed a significant association between Type 1 Diabetes mellitus (T1DM) and an increased risk of OLP, unlike Type 2 Diabetes mellitus (T2DM). This finding indicates a unique immunological interaction in T1DM that may predispose individuals to OLP. The drug prediction analysis focused on core targets linked to OLP and HbA1c, evaluating the therapeutic potential of retinoic acid, prednisone, and thalidomide for treating OLP and regulating blood glucose levels. Additionally, herbal medicines such as Ecliptae herbaand Amygdalus communis vas, along with herbal ingredients like quercetin, luteolin, and 17-beta-estradiol, were identified for their anti-inflammatory properties and potential to mitigate metabolic dysfunction in diabetes. Conclusion: The study highlighted a complex interplay between diabetes and OLP, underscoring the efficacy of integrated therapeutic strategies that target both conditions. The findings suggest that both pharmaceutical and herbal treatments can effectively manage the clinical manifestations of OLP and associated metabolic challenges. This holistic approach to treatment could significantly enhance patient outcomes by addressing the interconnected aspects of these chronic conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: FOXM1 is a pro-oncogenic transcription factor that is often upregulated in triple-negative breast cancer and aggressive solid cancers. FOXM1 drives cell proliferation, invasion, metastasis, drug resistance, and tumor growth and progression, and its expression is associated with poor prognosis and shorter patient survival. Therefore, FOXM1 is considered as an emerging therapeutic target. This review highlights the role of FOXM1, the mechanisms regulating its expression, its potential as a novel molecular target in TNBC and solid tumors, and attempts to develop FOXM1 inhibitors. Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, lacking common treatment targets such as estrogen (ER), progesterone (PR), and HER2 receptors. This subtype is associated with significant heterogeneity, chemoresistance, early recurrence, metastasis, and poor patient survival. FOXM1 is a cancer-promoting transcription factor that plays a critical role in TNBC and other highly aggressive cancers by driving cell proliferation, invasion, metastasis, and drug resistance. In TNBC, mutations in the TP53 gene—detected in approximately 80% of patients—lead to the overexpression of FOXM1, making it a promising therapeutic target. Beyond TNBC, FOXM1 is implicated in other solid cancers, such as brain (glioblastoma), lung, and pancreatic cancers, and is considered an Achilles' heel of aggressive cancers. Despite its potential as a therapeutic target, there are currently no FDA-approved FOXM1 inhibitors, and none have advanced to clinical trials. This review explores the role of FOXM1 in cancer progression and highlights the current status of efforts to develop effective FOXM1 inhibitors. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder responsible for over half of dementia cases, with two-thirds being women. Growing evidence from preclinical and clinical studies underscores the significance of sex-specific biological mechanisms in shaping AD risk. While older age is the greatest risk factor for AD, other distinct biological mechanisms increase the risk and progression of AD in women including sex hormones, brain structural differences, genetic background, immunomodulation and vascular disorders. Research indicates a correlation between declining estrogen levels during menopause and an increased risk of developing AD, highlighting a possible link with AD pathogenesis. The neuroprotective effects of estrogen vary with the age of treatment initiation, menopause stage, and type. This review assesses clinical and observational studies conducted in women, examining the influence of estrogen on cognitive function or addressing the ongoing question regarding the potential use of hormone replacement therapy (HRT) as a preventive or therapeutic option for AD. This review covers recent literature and discusses the working hypothesis, current use, controversies and challenges regarding HRT in preventing and treating age-related cognitive decline and AD. The available evidence indicates that estrogen plays a significant role in influencing dementia risk, with studies demonstrating both beneficial and detrimental effects of HRT. Recommendations regarding HRT usage should carefully consider the age when the hormonal supplementation is initiated, baseline characteristics such as genotype and cardiovascular health, and treatment duration until this approach can be more thoroughly investigated or progress in the development of alternative treatments can be made. [ABSTRACT FROM AUTHOR]

Objective: Hematologic malignancies in women of reproductive age carry significant additional morbidity due to menstrual bleeding in conjunction with disease and treatment-associated cytopenias. Several agents for menses prophylaxis and suppression exist, but there is a paucity of data comparing these therapies, particularly in the cancer setting. Data Sources: A thorough literature review and evaluation of available data was conducted via PubMed search and combined with clinical expertise. Data Summary: The goal of prophylaxis therapy is to induce amenorrhea until it is considered safe to resume menstrual cycles. GnRH agonists remain the management of choice in achieving menses control and amenorrhea. Suppression is more likely achieved when the therapy is initiated in the late luteal phase or with the concomitant use of oral contraceptives. The effective use of oral contraceptives is achievable in appropriately selected patients. Although attractive as prophylactic agents, GnRH agonists have a slow onset of amenorrhea and can be associated with an initial increase in bleeding, thus are of limited value in immediate menorrhagia management. We recommend prioritizing estrogen therapy given its documented efficacy, and adding tranexamic acid as a secondary agent for severe or refractory bleeding. Conclusions: Thus far in the literature, this is the most comprehensive proposed pathway for the prevention and suppression of menorrhagia in hematologic cancer patients. Our protocol provides a step-wise approach for the management of menses prophylaxis and suppression to provide standardization amongst clinicians and adaptations for patient-specific needs. [ABSTRACT FROM AUTHOR]

Key content: Urethral caruncle is a common post‐menopausal finding.This common benign lesion can be mistaken as a malignancy.Management should be based on the patient's symptoms.Vaginal estrogen should be considered as first‐line management before surgical excision. Learning objectives: To evaluate the symptomatic presentation of urethral caruncle.To establish the differential diagnosis of a mass in the urethra.To review the management options of urethral caruncle including medical and surgical excision.To highlight primary care management of urethral caruncle. Ethical issues: Owing to poor recognition of urethral caruncle, many patients are put through the emotional distress of referral to cancer pathways.Surgery should be considered first line for large urethral caruncle or in symptomatic patients. [ABSTRACT FROM AUTHOR]

Background: Endometrial hyperplasia, characterized by excessive growth leading to endometrial thickening, is commonly observed in the premenopausal period. Its prevalence in postmenopausal women is approximately 15%, peaking between ages 50 and 60. This condition often manifests as abnormal uterine bleeding and can progress to malignancy, with varying risks depending on the type of hyperplasia. Purpose: This study aims to investigate the factors influencing endometrial thickness during the perimenopausal period and raise awareness among healthcare professionals about the importance of evaluating and caring for individuals with endometrial hyperplasia. Methods: Studies examining the association between various factors such as diabetes mellitus, hypertension, age, estrogen replacement therapy, anovulatory disorders, smoking, medications, genetic factors, and endocrine-related proteins and the development of endometrial hyperplasia were reviewed. The literature search encompassed relevant databases, including PubMed, Scopus, and Web of Science. Results: Research findings indicate significant associations between changes in gene expression of several factors and the development of endometrial hyperplasia. Notably, the risk of progression to cancer varies between non-atypical and atypical hyperplasia cases. Factors such as diabetes mellitus, hypertension, age, estrogen replacement therapy, anovulatory disorders, smoking, medications, Lynch syndrome, tamoxifen use, and alterations in gene expression of TNF-α, EGF, IGF-1, IGF-1R, and PTEN have been implicated in the pathogenesis of endometrial hyperplasia. Conclusion: This study underscores the importance of understanding the factors influencing endometrial thickness during the perimenopausal period. It emphasizes the pivotal role of healthcare professionals in evaluating and caring for individuals with this condition. [ABSTRACT FROM AUTHOR]

BACKGROUND: A broad suite of bisphenol S (BPS) derivatives as alternatives for BPS have been identified in various human biological samples, including 4-hydroxyphenyl 4-isopropoxyphenylsulfone (BPSIP) detected in human umbilical cord plasma and breast milk. However, very little is known about the health outcomes of prenatal BPS derivative exposure to offspring. OBJECTIVES: Our study aimed to investigate the response of hepatic cholesterol metabolism by sex in offspring of dams exposed to BPSIP. METHODS: Pregnant ICR mice were exposed to 5μg/kg body weight (BW)/day of BPSIP, BPS, or E2 through drinking water from gestational day one until the pups were weaned. The concentration of BPSIP, BPS, or E2 in the plasma and liver of pups was determined by liquid chromatography-tandem mass spectrometry. Metabolic phenotypes were recorded, and histopathology was examined for liver impairment. Transcriptome analysis was employed to characterize the distribution and expression patterns of differentially expressed genes across sexes. The metabolic regulation was validated by quantitative real-time PCR, immunohistochemistry, and immunoblotting. The role of estrogen receptors (ERs) in mediating sex-dependent effects was investigated using animal models and liver organoids. RESULTS: Pups of dams exposed to BPSIP showed a higher serum cholesterol level, and liver cholesterol levels were higher in females and lower in males than in the controls. BPSIP concentration in the male liver was 1.22±0.25 ng/g and 0.69±0.27 ng/g in the female liver. Histopathology analysis showed steatosis and lipid deposition in both male and female offspring. Transcriptome and gene expression analyses identified sex-specific differences in cholesterol biosynthesis, absorption, disposal, and efflux between pups of dams exposed to BPSIP and those in controls. In vivo, chromatin immunoprecipitation analysis revealed that the binding of ERα protein to key genes such as Hmgcr, Pcsk9, and Abcg5 was attenuated in BPSIP-exposed females compared to controls, while it was enhanced in males. In vitro, the liver organoid experiments demonstrated that restoration of differential expression induced by BPSIP in key genes, such as Hmgcr, Ldlr, and Cyp7a1, to levels comparable to the controls was only achieved when treated with a combination of ERα agonist and ERβ; agonist. DISCUSSION: Findings from this study suggest that perinatal exposure to BPSIP disrupted cholesterol metabolism in a sex-specific manner in a mouse model, in which ERa played a crucial role both in vivo and in vitro. Therefore, it is crucial to systematically evaluate BPS derivatives to protect maternal health during pregnancy and prevent the transmission of metabolic disorders across generations [ABSTRACT FROM AUTHOR]

The article provides an update on recent advancements in menopause care, focusing on treatments for genitourinary syndrome of menopause (GSM), menopausal hormone therapy (MHT) outcomes in older women, and the efficacy of nonhormonal drugs. Topics discussed include the safety of vaginal estrogen therapy for women with a history of breast cancer, the effectiveness of fractional CO2 laser therapy, and the role of fezolinetant in managing vasomotor symptoms.

Purpose: (1) to compare clinical, biochemical features in female patients with hypoestrogenism due to childhood- and adult-onset CP; (2) to reveal effects of estrogen replacement therapy in female patients with childhood-onset CP. Methods: Thirty-seven women that received specific treatment for CP in the period from 1980 to 2019 were recruited: 21 with childhood-onset and 16 with adult-onset CP. Clinical and hormonal characteristics were evaluated. Seventeen-beta-estradiol 2 mg and dydrogesterone 10 mg in sequential regiment was used in 18 childhood-onset cases. Mean follow-up was 31 months. Results: Amenorrheic women with childhood- and adult-onset CP presented with the same complaints except for lack of genital hair and breast hypoplasia, which were common in patients with childhood-onset CP. BMI was lower in childhood-onset CP group, as was the proportion of overweight patients. They had more favorable lipid profile. The levels of estradiol, testosterone and DHEA-S were low and did not differ. Uterine and ovary volumes were reduced in all patients, but the decline was noticeable in the childhood-onset group. Mineral bone density of lumbar vertebrae was diminished in childhood-onset group. Estrogen therapy in these patients led to clinical improvement: increase in BMD in lumbar spine without negative changes in BMI and/or lipid profile. Conclusions: Study showed that women with childhood-onset CP had less negative metabolic changes. However, they have more pronounced breast and uterus hypoplasia and lower BMD in lumbar spine. The estrogen replacement therapy led to clinical improvement and BMD increase in lumbar spine without increase of BMI and/or lipid profile changes. [ABSTRACT FROM AUTHOR]

Background: As transgender people initiate gender-affirming hormone therapy (GAHT), they are exposed to exogenous sex hormones that have effects that have not yet been fully studied. While exogenous estrogen is associated with a risk of venous thrombosis, the full impact of estrogen on the liver is unknown. Conversely, the erroneous attribution of risks from GAHT presents a barrier to treatment for some patients. We present a case of obliterative portal venopathy (OPV) and possible DILI occurring after the initiation of estrogen in a transgender woman. Case presentation: A 28-year-old transgender woman on GAHT was referred to hepatology for liver enzyme elevations. She did not have any notable comorbid conditions, family history, or psychosocial history. Lab and imaging workup were unremarkable, and the patient underwent liver biopsy. The patient's biopsy results showed OPV. The patient continued GAHT at a lower dose and liver enzyme elevations resolved. Conclusions: OPV is a vascular disease that falls under the category of porto-sinusoidal vascular disorder. Patients with this condition can present with or without overt clinical signs of portal hypertension. Porto-sinusoidal vascular disorder is rare and given the timing and possible dose dependence, it might be reasonable to consider that the observed OPV was influenced by the exogenous estrogen administered in an association not previously reported. Alternatively, the patient's continued estrogen treatment without ill effect could suggest that the events were not connected and that the fear of harm could have served as a barrier to the patient receiving indicated care. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the risk of osteoarthritis associated with menopausal hormone therapy (MHT). Methods: This population-based retrospective cohort study used a database of Korean health insurance claims (2007--2020). Females aged ≥ 40 who initiated menopause-related healthcare visits between 2011 and 2014 were identified. The MHT group comprised females aged ≥ 40 who initiated MHT for ≥ 6 months during this period. The non-MHT group comprised females aged ≥ 40 who attended menopause-related healthcare visits but did not receive MHT. To account for potential confounding factors, the two groups were matched at a 1:1 ratio using propensity score matching. Results: A cohort of 453,040 postmenopausal females aged ≥ 40 years was identified, with 26,354 assigned to either the MHT or non- MHT group after propensity matching. The median age was 49 years, and the median follow-up was 8.2 years. The Cox proportional hazards model demonstrated an elevated risk of osteoarthritis with MHT (hazard ratio [HR], 1.154; 95% confidence interval [CI], 1.117--1.193) for knee (HR, 1.148; 95% CI, 1.102--1.195) and other arthritis (HR, 1.205; 95% CI, 1.151--1.261), although not statistically significant for hip arthritis. Tibolone (HR, 1.211; 95% CI, 1.161--1.263), estrogen--progestogen therapy (EPT) (HR, 1.092; 95% CI, 1.048-- 1.137), and estrogen therapy (ET) (HR, 1.235; 95% CI, 1.148--1.329) were associated with a higher risk of osteoarthritis compared to non- MHT users. Conclusions: MHT was associated with an increased risk of osteoarthritis, consistently observed across tibolone, EPT, and ET, particularly affecting joints other than the hip, with a trend toward an elevated risk of hip osteoarthritis. [ABSTRACT FROM AUTHOR]

Approximately 0.6% of the United States population identifies as transgender or gender nonbinary. The term transgender refers to a person who experiences incongruence between their sex at birth and their gender identity. The care of the transgender patient is complex, often requiring the expertise of various medical and surgical specialties. The prevalence of gender-affirming surgery is increasing as societal acceptance and cultural norms are shifting. While gender-affirming procedures include a variety of body systems, airway and facial procedures are of particular importance to anesthesia providers. Anesthetic concerns for masculinization and feminization procedures of the airway and face include bleeding, injury to the airway, and other perioperative challenges. Transgender procedures of the airway and face often require advanced airway techniques. Following airway surgery, patients are at an increased risk for tracheal stenosis or perforation, glottic stenosis, vocal cord damage or dysfunction, and/or dysphagia. Additionally, transgender patients may undergo hormone therapy to achieve their gender goals. Providers should be aware of the implications associated with administration of hormones such as thromboembolic events, cardiovascular effects, and changes in various laboratory values. A knowledge of novel surgical procedures, medical therapies, and the psychosocial implications associated with transition is essential for the safe, comprehensive, and holistic care of the transgender patient. [ABSTRACT FROM AUTHOR]

Osteoporosis, a metabolic bone disorder characterized by decreased bone mass per unit volume, poses a significant global health burden due to its association with heightened fracture risk and adverse impacts on patients' quality of life. This review synthesizes the current understanding of the pathophysiological mechanisms underlying osteoporosis, with a focus on key regulatory pathways governing osteoblast and osteoclast activities. These pathways include RANK/RANKL/OPG, Wingless-int (Wnt)/β-catenin, and Jagged1/Notch1 signaling, alongside the involvement of parathyroid hormone (PTH) signaling, cytokine networks, and kynurenine in bone remodeling. Pharmacotherapeutic interventions targeting these pathways play a pivotal role in osteoporosis management. Anti-resorptive agents, such as bisphosphonates, estrogen replacement therapy/hormone replacement therapy (ERT/HRT), selective estrogen receptor modulators (SERMs), calcitonin, anti-RANKL antibodies, and cathepsin K inhibitors, aim to mitigate bone resorption. Conversely, anabolic agents, including PTH and anti-sclerostin drugs, stimulate bone formation. In addition to pharmacotherapy, nutritional supplementation with calcium, vitamin D, and vitamin K2 holds promise for osteoporosis prevention. However, despite the availability of therapeutic options, a substantial proportion of osteoporotic patients remain untreated, highlighting the need for improved clinical management strategies. This comprehensive review aims to provide clinicians and researchers with a mechanistic understanding of osteoporosis pathogenesis and the therapeutic mechanisms of existing medications. By elucidating these insights, this review seeks to inform evidence-based decision-making and optimize therapeutic outcomes for patients with osteoporosis. [ABSTRACT FROM AUTHOR]

Menopausal women may experience symptoms of depression, sometimes even progressing clinical depression requiring treatment to improve quality of life. While varying levels of estrogen in perimenopause may contribute to an increased biological vulnerability to mood disturbances, the effectiveness of estrogen replacement therapy (ERT) in the relief of depressive symptoms remains controversial. Menopausal depression has a complex, multifactorial etiology, that has limited the identification of optimal treatment strategies for the management of this psychiatric complaint. Nevertheless, clinical evidence increasingly supports the notion that estrogen exerts neuroprotective effects on brain structures related to mood regulation. Indeed, research using preclinical animal models continues to improve our understanding of menopause and the effectiveness of ERT and other substances at treating depression-like behaviors. However, questions regarding the efficacy of ERT in perimenopause have been raised. These questions may be answered by further investigation using specific animal models of reduced ovarian function. This review compares and discusses the advantages and pitfalls of different models emulating the menopausal stages and their relationship with the onset of depressive-like signs, as well as the efficacy and mechanisms of conventional and novel ERTs in treating depressivelike behavior. Ovariectomized young rats, middle-to-old aged intact rats, and females treated with reprotoxics have all been used as models of menopause, with stages ranging from surgical menopause to perimenopause. Additionally, this manuscript discusses the impact of organistic and therapeutic variables that may improve or reduce the antidepressant response of females to ERT. Findings from these models have revealed the complexity of the dynamic changes occurring in brain function during menopausal transition, reinforcing the idea that the best approach is timely intervention considering the opportunity window, in addition to the careful selection of treatment according to the presence or absence of reproductive tissue. Additionally, data from animal models has yielded evidence to support new promising estrogens that could be considered as ERTs with antidepressant properties and actions in endocrine situations in which traditional ERTs are not effective. [ABSTRACT FROM AUTHOR]

Background: Androgen blockers are an essential part of gender affirming care in post-pubertal transfeminine patients. Bicalutamide is a highly potent androgen receptor blocker that is used primarily in adults. We aimed to review our experience with the use of bicalutamide in transgender adolescents who were assigned male at birth. Methods: A retrospective review of medical records of transfeminine patients treated with bicalutamide during an 8-year period was conducted. Results: Forty patients, aged 15.5 ± 1.55 years were identified, of whom 21 (53%) were started on bicalutamide alone and 19 were started concurrently on estrogen. In patients on bicalutamide alone, 90.4% reported breast development at their first follow up visit, which occurred at a median of 7.1 months. Patients were treated for 29.4 ± 18.2 months. No episodes of liver toxicity related to bicalutamide were seen. Conclusions: Although these results are preliminary, bicalutamide appears to be a safe option for androgen blockade in transgender girls. [ABSTRACT FROM AUTHOR]

Perimenopausal depression (PMD) is a psychological disorder that occurs in women during perimenopause. In addition to the common clinical symptoms of depression, it often manifests as a perimenopausal complication, and its notable cause is the decline in estrogen levels. Despite numerous studies and trials confirming the benefits of estrogen replacement therapy (ERT) for PMD, ERT remains unapproved for treating PMD. Therefore, we conducted a literature search using selected keywords in PubMed and Google Scholar to write a review discussing the feasibility of using ERT for PMD. This review examines the potential of ERT for PMD in terms of its underlying mechanisms, efficacy, safety, and time window. These four aspects suggest that ERT is a viable option for PMD treatment. However, the risk of thrombosis and stroke with ERT is a matter of contention among medical experts, with a paucity of clinical data. Consequently, further clinical trial data are required to ascertain the safety of ERT. [ABSTRACT FROM AUTHOR]

Longitudinal bone growth is mediated through several mechanisms including macro- and micronutrients, and endocrine and paracrine hormones. These mechanisms can be affected by childhood obesity as excess adiposity may affect signaling pathways, place undue stress on the body, and affect normal physiology. This review describes the physiology of the epiphyseal growth plate, its regulation under healthy weight and obesity parameters, and bone pathology following obesity. A literature review was performed utilizing PubMed, PMC, NIH, and the Cochrane Database of Systematic Reviews pertinent to hormonal and nutritional effects on bone development, child obesity, and pathologic bone development related to weight. The review indicates a complex network of nutrients, hormones, and multi-system interactions mediates long bone growth. As growth of long bones occurs during childhood and the pubertal growth spurt, pediatric bones require adequate levels of minerals, vitamins, amino acids, and a base caloric supply for energy. Recommendations should focus on a nutrient-dense dietary approach rather than restrictive caloric diets to maintain optimal health. In conclusion, childhood obesity has profound multifaceted effects on the developing musculoskeletal system, ultimately causing poor nutritional status during development. Weight loss, under medical supervision, with proper nutritional guidelines, can help counteract the ill effects of childhood obesity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The menopausal transition results in a progressive decrease in circulating estrogen levels. Experimental evidence in rodents has indicated that estrogen depletion leads to a reduction of energy expenditure and physical activity. It is unclear whether treatment with estrogen therapy increases physical activity level in postmenopausal women. METHODS: A total of 27,327 postmenopausal women aged 50-79 years enrolled in the Womens Health Initiative randomized double-blind trials of menopausal hormone therapy. Self-reported leisure-time physical activity at baseline, and years 1, 3, and 6 was quantified as metabolic equivalents (MET)-h/wk. In each trial, comparison between intervention and placebo groups of changes in physical activity levels from baseline to follow-up assessment was examined using linear regression models. RESULTS: In the CEE-alone trial, the increase in MET-h/wk was greater in the placebo group compared with the intervention group at years 3 ( P = 0.002) and 6 ( P < 0.001). Similar results were observed when analyses were restricted to women who maintained an adherence rate ≥80% during the trial or who were physically active at baseline. In the CEE + MPA trial, the primary analyses did not show significant differences between groups, but the increase of MET-h/wk was greater in the placebo group compared with the intervention group at year 3 ( P = 0.004) among women with an adherence rate ≥80%. CONCLUSIONS: The results from this clinical trial do not support the hypothesis that estrogen treatment increases physical activity among postmenopausal women.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a recently described neuropathological construct associated with dementia. This study aimed to investigate in an autopsy study, LATE-NC and its associations with potential estrogen-related risk factors collected about 30 years before death. Participants were part of The 90+ Study and had, as part of the Leisure World Cohort Study, provided information on menstrual and reproductive variables and details of use of estrogen replacement therapy (ERT). No menstrual and reproductive variable showed an association with LATE-NC. Use of ERT, especially long-term use (15+ years) and more recent use (within 1 year of completing the questionnaire), was associated with reduced risk. The odds were significantly lower for long-term (0.39, 95% confidence interval [CI]: 0.16-0.95) and recent use (0.39, 95% CI: 0.16-0.91) compared with no use. In conclusion, we found that women who reported long-term ERT in their 50s and 60s had a significantly reduced odds of harboring LATE-NC when they died in the 10th and 11th decades of their lives. Our study adds to the existing literature reporting seemingly protective effect of peri- and postmenopausal ERT against neurodegenerative dementia.

Purpose: Facet joint degeneration (FJD) is a major cause of low back pain. Parathyroid hormone (PTH) (1–34) is commonly used to treat osteoporosis. However, little is known about its effects on FJD induced by estrogen deficiency. This study aims to investigate the effects of PTH (1–34) on FJD induced by estrogen deficiency and the underlying pathogenesis of the disease. Methods: Forty 3-month-old female Sprague-Dawley rats were randomly divided into four groups: 30 received bilateral ovariectomy (OVX) followed by 12 weeks of treatment with normal saline, PTH (1–34) or 17β-estradiol (E2), and 10 received sham surgery followed by administration of normal saline. Status and Wnt/β-catenin signaling activity in the cartilage and subchondral bone of the L4–L5 FJs and serum biomarkers were analyzed. Results: Administration of PTH (1–34) and E2 ameliorated cartilage lesions, and significantly decreased MMP-13 and caspase-3 levels and chondrocyte apoptosis. PTH (1–34) but not E2 significantly increased cartilage thickness, number of chondrocytes, and the expression of aggrecan. PTH (1–34) significantly improved microarchitecture parameters of subchondral bone, increased the expression of collagen I and osteocalcin, and decreased RANKL/OPG ratio. E2 treatment significantly increased the OPG level and decreased the RANKL/OPG ratio in the subchondral bone of ovariectomized rats, but it did not significantly improve the microarchitecture parameters of subchondral bone. Wnt3a and β-catenin expression was significantly reduced in the articular cartilage and subchondral bone in OVX rats, but PTH (1–34) could increase the expression of these proteins. E2 significantly increased the activity of Wnt/β-catenin pathway only in cartilage, but not in subchondral bone. The restoration of Wnt/β-catenin signaling had an obvious correlation with the improvement of some parameters associated with the FJs status. Conclusion: Wnt/β-catenin signaling may be a potential therapeutic target for FJD induced by estrogen deficiency. PTH (1–34) is effective in treating this disease with better efficacy than 17β-estradiol, and the efficacy may be attributed to its restoration of Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Alzheimer's Diseases are one of the most serious brain condition affecting senior peoples. Improved cognitive disorders therapy, better behaviour and clinical diagnostic standard are recent breakthrough. Placebocontrolled, double--blind, Randomised, parallel group studies evaluating performance -based assessment of cognitive function, activities of daily living and behaviour have been used to clinically evaluate symptomatic treatment that focuses on cholinergic therapy. Patient of Alzheimer's disease are advised to use cholinesterase inhibitors, such as ntamine and tacrine, to address cognitive impairment. Antipsychotics, anxiolytics, antidepressants, mood stabilizer and hypnotics are used in treatment of behavioural disturbance. Evaluation in research and treatment of patients of Alzheimer's disease includes: Applying functional brain imaging techniques and evaluation of treatment efficacy. Development of new classes of medications works on different neurotransmitter systems, for the treatment of cognitive deficits and behavioural disturbance. [ABSTRACT FROM AUTHOR]

The article presents a study on trends in estrogen therapy (ET) use from a sample of ambulatory care visits to evaluate co-prescription of ET and sedating potentially inappropriate medications (PIMS) and assess whether ET was a marker for polypharmacy in women aged 65 and older. Topics include demographic and clinical characteristics of 2006-2016 ambulatory visits, prevalence of estrogen prescribing in ambulatory visits, and association between ET and polypharmacy.

Background: Almost 10% of women in reproductive age are diagnosed with ovarian endometriomas and can experience symptoms and infertility disorders. Ovarian endometriomas can be treated with medical or surgical therapy. Objective: To assess whether long-term therapy with dienogest or oral cyclic estrogen-progestogens is effective in reducing the size of ovarian endometriomas, alleviating associated symptoms, and reducing the requirement for surgery. Design: Prospective non-interventional cohort study. Methods: We enrolled childbearing women diagnosed with ovarian endometriomas. We collected demographic, clinical, and surgical data, including the evaluation of ovarian endometrioma-associated symptoms and pain using the visual analog scale. We grouped the women according to treatment regimen into dienogest, estrogen-progestogens, and no-treatment. Patient's assessment was performed at baseline and after 12 months evaluating the largest ovarian endometrioma diameter (in millimeters) and the associated symptoms. Furthermore, we analyzed the impact of hormonal treatment in a sub-group of women fulfilling at baseline the criteria for a first-line surgical approach (ovarian endometrioma > 30 mm with visual analog scale > 8 or ovarian endometrioma > 40 mm before assisted reproductive treatments or any ovarian endometrioma(s) > 60 mm). Results: We enrolled 142 patients: 62, 38, and 42 in dienogest, estrogen-progestogens, and no-treatment groups, respectively. No significant differences were found regarding baseline characteristics. After 12 months, the mean largest ovarian endometrioma diameter increased in the no-treatment group (31.1 versus 33.8; p < 0.01), while a significant reduction was registered in the dienogest (35.1 versus 25.8; p < 0.01) and estrogen-progestogens (28.4 versus 16.7; p < 0.01) groups; no significant difference in ovarian endometrioma diameter reduction between these two latter groups was noted (p = 0.18). Ovarian endometrioma-associated symptoms and pain improved in dienogest and estrogen-progestogens groups, with a significantly greater effect for dienogest than for estrogen-progestogens for dysmenorrhea (74% versus 59%; p < 0.01). In the sub-group of women eligible for first-line surgery at baseline, long-term treatment with dienogest and estrogen-progestogens reduced surgical eligibility by 30%. Conclusions: Decreased mean largest ovarian endometriomas'diameter after 12 months and reduction of the need for surgical treatment by 30% were observed in dienogest and estrogen-progestogens groups. Long-term treatment with dienogest had a greater effect in alleviating dysmenorrhea and pain. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Sichuan University (Medical Science Edition) is the property of Editorial Board of Journal of Sichuan University (Medical Sciences) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: This work challenges the traditional principles of cancer therapy: simply targeting and blocking the regulatory pathways of rapidly proliferating tumors is a serious mistake. Since tumor initiation and growth may be attributed to a patient's genomic instability and damage, genotoxic medications are inappropriate as they cause additional genomic damage in both patients and their cancers. Tumor cells are not enemies to be killed, but rather they are ill human cells which have the remnants of same genome stabilizer pathways like healthy cells. Within tumors, there is a combat for the improvement of their genomic defects. Moreover, tumors ask for help in their kamikaze action by recruiting immune competent cells into their environment. We should learn by watching the genome repairing activities within tumors, in the peritumoral region and in the whole body, and may follow them with supportive care. Successful cancer therapy does not remain a dream to be realized in the far future, but we should set about a cancer cure without delay. Background: In tumors, somatic mutagenesis presumably drives the DNA damage response (DDR) via altered regulatory pathways, increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation-activated DNA repair pathways of tumors.Purpose: Justifying that cancer cells are not enemies to be killed, but rather that they are ill human cells which have the remnants of physiologic regulatory pathways. Results: 1. Genomic instability and cancer development may be originated from a flaw in estrogen signaling rather than excessive estrogen signaling; 2. Healthy cells with genomic instability exhibit somatic mutations, helping DNA restitution; 3. Somatic mutations in tumor cells aim for the restoration of DNA damage, rather than further genomic derangement; 4. In tumors, estrogen signaling drives the pathways of DNA stabilization, leading to apoptotic death; 5. In peritumoral cellular infiltration, the genomic damage of the tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, an increased growth factor receptor (GFR) signaling confers the unliganded activation of estrogen receptors (ERs); 6. In breast cancer cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signaling and consequential apoptosis. In breast tumors non-responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathways are exhausted, leading to farther genomic instability and unrestrained proliferation. Conclusions: Understanding the real character and behavior of human tumors at the molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy, rather than provoking additional genomic damages. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck tumors (HNTs) represent a diverse group of malignancies that originate from the lining tissue of organs in the upper parts of the respiratory and digestive tracts. Given that these include parts of the body that enable breathing, speech, and feeding, these tumors cause a great reduction in the quality of life. The main risk factors are consumption of tobacco products and alcohol, as well as infection with human papillomaviruses. However, regardless of the risk factors, men have a significantly higher risk of developing HNTs than women. It is, therefore, presumed that exposure to the female sex hormone estrogen in women could provide protection against the development of those tumors in women. In this scientific literature survey, we provide a comprehensive overview of the role of estrogen and its receptors in HNTs and assess the possible benefits of therapy with either exogenous estrogen or anti-estrogens. Head and neck squamous cell carcinoma (HNSCC) is the most common histological form of head and neck tumors (HNTs), which originate from the epithelium of the lips and oral cavity, pharynx, larynx, salivary glands, nasal cavity, and sinuses. The main risk factors include consumption of tobacco in all forms and alcohol, as well as infections with high-risk human papillomaviruses or the Epstein–Barr virus. Regardless of the etiological agent, the risk of developing different types of HNTs is from two to more than six times higher in males than in females. The reason for such disparities probably lies in a combination of both biological and psychosocial factors. Therefore, it is hypothesized that exposure to female sex hormones, primarily estrogen, provides women with protection against the formation and metastasis of HNTs. In this review, we synthesized available knowledge on the role of estrogen and estrogen receptors (ERs) in the development and progression of HNTs, with special emphasis on membrane ERs, which are much less studied. We can summarize that in addition to epidemiologic studies unequivocally pointing to the protective effect of estrogen in women, an increased expression of both nuclear ERs, ERα, and ERβ, and membrane ERs, ERα36, GPER1, and NaV1.2, was present in different types of HNSCC, for which anti-estrogens could be used as an effective therapeutic approach. [ABSTRACT FROM AUTHOR]

Recently, with discriminatory legislation efforts and changing participation policies in organized sports, media attention surrounding transgender and gender-diverse (TGD) individuals has increased. These changes and the historical lack of competence and education regarding the transgender patient population have resulted in subpar patient care and a misunderstanding of the athletic trainer's (AT's) role within the health care and compliance systems. This literature review is the second part of a 2-paper series, and our objective was to educate ATs on the processes relevant to medical affirmation, including compliance considerations regarding medical eligibility, and to establish the AT's role. The gender affirmation framework includes social and legal components, which are discussed in part 1 of this literature, and the medical component is thoroughly discussed in part 2. All health care providers involved in the care of TGD individuals should work collaboratively on an interprofessional care team and have a general knowledge of the gender-affirmation process, including gender-affirming hormone therapy, surgical options, known risks and complications, and the general health needs of TGD patients. With this knowledge, ATs, as point-of-care providers and members of the interprofessional care team, are uniquely positioned to help reduce health and health care disparities. Furthermore, ATs can use their knowledge to facilitate medical compliance and eligibility in the evolving policies of sporting organizations. [ABSTRACT FROM AUTHOR]

Copyright of Lege Artis Medicine (LAM) is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ObjectivesTwo-thirds of individuals living with Alzheimer's disease are women. Declining estrogen levels influence mood and cognition. Cumulative lifetime estrogen exposure (CLEE) correlates with cognition later in life. We examined the relationship of CLEE to depression and cognition in older women with major depression compared to non-depressed women.DesignOlder women (age ≥60 years) with depression were compared to non-depressed women using a lifetime estrogen exposure questionnaire. CLEE was defined as combined durations of reproductive span (age of menopause minus age of menarche) and any post-menopausal hormone replacement therapy use. Higher vs lower CLEE groups were based on a median of 474 months of estrogen exposure.SettingUniversity hospital outpatient research program.Participants135 women ≥60 years; 64 depressed and 71 non-depressed.MeasurmentsParticipants completed a comprehensive cognitive test battery. General linear models were used to examine the association between cognitive domain scores and CLEE in depressed and non-depressed women, controlling for age, education, and ethnicity.ResultsDepressed and non-depressed groups had significantly different levels of CLEE, measured in months: mean 495.7 (SD 108.6) vs 456.4 (SD 66.0) months, F(1,130) = 5.01, p = .03. Within the non-depressed participants, higher CLEE was associated with improved delayed recall (F(1,59) = 5.94, p = .02, effect size = .61), while no such relationship was observed in the depressed group.ConclusionHigher CLEE was associated with improvement in delayed recall among non-depressed, but not among depressed participants. This suggests a protective role of estrogen on memory in non-depressed older postmenopausal women. Further research should examine the role of the CLEE in antidepressant response and cognitive decline.

Abstract Background Estrogen replacement therapy (ERT) is a common hormonal treatment for postmenopausal women, aimed at alleviating menopausal symptoms and reducing the health risks associated with estrogen deficiency. However, the impact of ERT on temporomandibular disorders (TMDs) remains unclear. This systematic review aims to evaluate the relationship between ERT and TMDs, including TMD occurence, pain, and associated symptoms. Methods A comprehensive search of seven electronic databases was conducted using predefined search terms and Boolean operators. Inclusion criteria encompassed studies examining the association between ERT and TMDs. Two independent reviewers screened the identified articles, extracted data, and assessed the risk of bias using the RoB -2 tool. Results Search strategy identified a total of 3 articles which met the inclusion criteria. The included studies investigated the impact of ERT on TMD occurrence and its related symptoms. The analysis revealed no significant association between ERT and TMD occurrence. A significant dose relationship was noted in one of the studies while another mentioned the possible relationship of TMD with educational status. Risk of bias among the studies was low, and the overall quality of evidence was deemed to be high. Conclusion This systematic review suggests that there is no conclusive evidence supporting an increased risk of TMDs among women receiving ERT. The findings indicate that ERT is unlikely to have a noticeable impact on TMDs. However, due to the limited number of studies available, further research is warranted to strengthen these conclusions and explore potential factors that may influence the relationship between ERT and TMDs.

This review summarizes our current understanding of associations of the postmenopausal vaginal microbiome with genitourinary syndrome of menopause. We review the normal postmenopausal microbiota, examine the association of the microbiome with vulvovaginal symptoms, describe microbial communities associated with physical and laboratory findings, and report the impact of different treatments for genitourinary syndrome of menopause on microbiota and symptom improvement. Postmenopausal vaginal symptoms have an underlying pathophysiology that has not been fully elucidated. Estrogen treatment may not be sufficient to relieve symptoms of vaginal discomfort in all postmenopausal individuals. In addition, other interventions targeted at changing the microbiota or pH do not consistently improve symptom severity. [ABSTRACT FROM AUTHOR]

Scientific information is incomplete regarding the genitourinary syndrome of menopause. Both the lower genital and urinary tracts are rich in receptors for reproductive hormones and are highly susceptible to waning ovarian hormones at menopause. Symptoms of dryness and pain emerge in late perimenopause, but they can also result earlier from cancer therapies or bilateral oophorectomy. Lower urinary tract symptoms rise in prevalence at midlife and increase further with advancing age. Because ovarian senescence is typically followed by years of aging, some postmenopausal complaints may be attributable to increasing longevity. [ABSTRACT FROM AUTHOR]

As the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery. The MarketScan Database was used to identify patients 18–49 years who underwent hysterectomy plus oophorectomy and those aged 50–75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests. A total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was −37.1% (95% CI, −40.5 to −33.6%) for patients 18–49 years of age and − 10.4% (95% CI, −10.9 to −9.9%) for those 50–75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50–75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18–49 years of age (P =.02) and those 50–75 years of age (P <.001). The use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer. • Use of nonhormonal medications among pre- and postmenopausal uterine cancer patients after hysterectomy has increased. • Use of estrogen replacement therapy for uterine cancer patients has declined over time. • Estrogen therapy is used less commonly after hysterectomy for uterine cancer than in patients with benign diseases. [ABSTRACT FROM AUTHOR]

Vasomotor symptoms (VMS) associated with menopause usually reduce the quality of life of women, generating eloquent discomfort. Menopausal hormone therapy (MHT) is the standard in the treatment of menopausal symptoms, being the only treatment that has been shown to be effective for VMS. Objective: to describe the efficacy and safety of transdermal menopausal hormone therapy (THM TD) to relieve menopausal symptoms. Methods: a systematic review of the literature was carried out in different electronic databases (CINAHL Plus, EMBASE, Scopus, Lilacs, Medline, Pubmed, among others), through standardized search terms. The outcomes evaluated included studies where any treatment or intervention with TD MHT was published in women treated for menopausal symptoms, percentages of relief of climacteric symptoms and proportion of associated adverse events. Results: 45 publications were included, and they agree in advising treatment with MHT TD, in view of a relief of climacteric symptoms close to 90%, as well as being safer and potentially more effective than oral therapy; with normal results in mammographic evaluation, and without related adverse events after 5 years of follow-up. Conclusions: transdermal hormonal therapy in menopause is safe and effective in relieving menopause symptoms. By avoiding hepatic metabolism, it achieves better clinical benefits, while minimizing the exposure to adverse events. The reviewed publications demonstrate that the transdermal route is the best way to treat menopause symptoms. [ABSTRACT FROM AUTHOR]

Objective To systematically evaluate the risk of estrogen use and ovarian cancer in postmenopausal women. Methods PubMed, Cochrane, Embase databases and Chinese databases such as CNKI, VIP, and Wan fang were searched by computer. Studies on the correlation between estrogen replacement therapy and ovarian cancer in postmenopausal women up until January 2023 were collected. The methodological quality of the study was evaluated by Stata software and the effective data were extracted for meta-analysis. We used the odds ratio (OR) and its corresponding 95% confidence interval (Cls) to evaluate the relationship between hormone replacement therapy and ovarian cancer. When there was statistical heterogeneity between studies (P≤0.1 and F 40%), random effect model was used for meta-analysis; otherwise, fixed effect model was used for analysis. Results A total of 14 retrospective studies including 10 cohort studies and 4 case-control studies were identified. Meta-analysis showed that postmenopausal estrogen therapy increased the risk of ovarian cancer in women (OR=1.27, 95%CI: 1.14-1.43). Stratified analysis showed that there was no significant increase in the risk of ovarian cancer in postmenopausal women who took estrogen for less than 5 years (OR=1.04, 95%CI: 0.90-1.20). Postmenopausal women who received estrogen treatment for 5 to 10 years had a significantly increased risk of developing ovarian cancer (OR=1.27, 95%CI: 1.06-1.53). Post- menopausal women who had been treated with estrogen for more than 10 years had a significantly increased risk of ovarian cancer (OR=1.69, 95%CI: 1.42-2.02). Conclusion The risk of ovarian cancer in postmenopausal women treated with estrogen re- placement therapy is related to the course of estrogen therapy. There is no significant increase in the risk of ovarian cancer within 5 years, but the risk of ovarian cancer is significantly increased when the course of treatment exceeds 5 years. [ABSTRACT FROM AUTHOR]

Background: Successful implantation of the embryo and normal development of pregnancy after hysteroscopic metroplasty in women with congenital uterine anomalies, obtaining a normal endometrium is a necessary condition, which must be achieved by preventing development of postoperative intrauterine adhesions (IUA) and stimulating regeneration of the endometrium. Despite years of studies aimed at evaluating strategies to prevent IUA after operative hysteroscopy, it is still unclear which strategies are most effective. Aim: The aim of this literature review is to analyze and evaluate advantages and disadvantages of therapeutic means used for prevention of development of IUA after hysteroscopic metroplasty and to stimulate the regeneration of the endometrium Methods: In order to collect literature data, we used such electronic search databases as PubMed, Medline, Google Scholar and Cochrane Library. Key words used were: congenital uterine anomalies. Hysteroscopy, metroplasty, intrauterine adhesion, anti-adhesion therapy, endometrial regeneration. Results: From 136 articles retrieved, we selected 62 articles and included them in our review. Analysis of selected literary sources revealed that use of mechanical barriers against IUA in postoperative period does not provide additional positive benefits in terms of reduction of spontaneous abortions, development of spontaneous pregnancy and increase of the rate of live birth. Their role in reducing development of IUA is also controversial. Also, use of mechanical barriers in combination with estrogen therapy did not show reliably high results in terms of improving female reproductive function. Regarding positive therapeutic effect of anti- adhesion gels, by analyzing reviewed literature sources, we obtained contradictory results. As for the effectiveness of using anti-adhesion gels with estrogen therapy after metroplasty, postoperative treatment with similar combination could not be seen in the literature sources. It should be noted that available literature has significant heterogeneity and a high risk of bias, which makes it difficult to draw final conclusions and does not allow for elaboration of optimal postoperative management scheme. Conclusion: Based on the analysis of literature sources it is clear that more randomized control trials are needed to evaluate effectiveness of different anti-adhesion means both as monotherapy and in combination. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association.MethodsWe conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs).ResultsOverall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99).ConclusionsThe hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.

Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values

Objective To establish a rat model of postmenopausal sarcopenia and explore the therapeutic effect of estrogen supplementary therapy on the disease. Methods ① Forty-four 12-week-old female SD rats (220±20 g) were randomly divided into sham group and ovariectomized (OVX) group by stratified random sampling based on body weight, with 22 rats in each group. The rats of the OVX group were given bilateral ovariectomy, while those of the SHAM group underwent sham surgery. The body weight was monitored, and the grip strength of the forelimb was measured using an electronic grip strength meter. In 12 weeks after surgery, the body composition was analyzed by X-ray absorptiometry (DXA) to identify the model establishment by relative lean mass. Ten rats in each group were sacrificed to harvest the gastrocnemius, and then sarcopenia index (SI) was calculated as the ratio of gastrocnemius mass to body weight. HE staining and transmission electron microscopy were applied respectively to observe the cross-sectional area of the muscle fibers and the structure of myofibrils were determined. ② The remaining rats were further divided into SHAM group, SHAM+O group, OVX group and OVX+E2 group, with 6 rats in each group. 17β-estradiol was injected subcutaneously in OVX+E2 group, while control solvent (10% DMSO+90%sesame oil) was injected subcutaneously in SHAM+O group. The grip strength and body composition were measured and body composition was analyzed. ELISA was used to measure the serum levels of E2 and FSH, HE staining was employed to observe the cross-sectional area of gastrocnemius muscle fibers, electron microscopy was conducted to observe the ultrastructure of myofibrils, and immunofluorescence staining was applied to analyze the expression of Bax and Bcl-2. Results ① After 12 weeks of modeling, the rats in the OVX group had significant lower relative lean mass (P < 0.001), indicating the successful establishment of sarcopenia model, and had obviously increased body weight (P < 0.001) and body fat rate (P < 0.001), but decreased relative grip (P < 0.001), SI value, average cross sectional area of the muscle fibers (P < 0.01), and mitochondrial density (P=0.012). ② Estrogen supplementary therapy resulted in similar body weight, body fat rate, grip strength, relative lean mass, SI value, average cross sectional area of the muscle fibers, and mitochondrial density in the rats in OVX+E2 group when compared with those of SHAM group. Immunofluorescence assay re vealed that OVX group had a notably lower Bcl-2/Bax ratio than the SHAM and OVX+E2 groups (P < 0.01). Conclusion A rat model of postmenopausal sarcopenia is successfully established. Estrogen supplementary therapy can significantly improve the muscle mass loss in ovariectomized rats, which may be associated with estrogen inhibiting myocyte apoptosis.

Abstract Background 17β-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown. Methods In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC–MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro. Results sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression. Conclusion These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.

Background: The ovarian follicular cell's degradation and subsequent decrease in the synthesis of estrogen results in the decreased cardiovascular protection. As a result, the incidence of cardiovascular disease (CVD) increases in postmenopausal women and is characterized by change in lipid profile. This study sought to ascertain the extent of the impact that menstrual status might have on lipid profiles among premenopausal and postmenopausal women. Methods: A cross-sectional study was conducted with 260 premenopausal and postmenopausal women (1: 1) and serum lipid component concentrations (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), and total cholesterol (TC)) were measured. A comparison between two groups was made between premenopausal and postmenopausal women, and regression was carried out to estimate the effect of menstrual status on lipid components. Results: Compared with premenopausal women, the concentrations of the lipid components (HDL-C, LDL-C, TG, and TC) were found to be significantly higher in postmenopausal women. Using the linear regression, menstruation status was able to predict 11.7%–13.3% of the lipid components (TG and TC) when age and weight were adjusted. Conclusion: The difference in lipid components between premenopausal women and postmenopausal women exists, with menstrual status explaining 11.7%–13.3% variance for the observed lipid level. The factors influencing the lipid profile beside the menstrual status should also be explored. External intervention such as estrogen replacement therapy is also recommended in case of deviation of lipid profile from the suggested normal clinical range. [ABSTRACT FROM AUTHOR]

Sea buckthorn (Hippophae rhamnoides L.) is a flowering shrub, and its berries have been utilized for decades as a raw ingredient in cuisines and herbal remedies. This evidence-based study focuses on its key bioactive constituents, and mechanism of protective effects with a focus on female reproductive processes. Parts of the plant contain phenols, carotenoids (lycopene, carotene, lutein, and zeaxanthin), flavonoids (isorhamnetin, quercetin, glycosides, and kaempferol), tocopherols, sterols, polyunsaturated fatty acids, minerals, vitamins, omega 3, 6, 9 and rare omega 7 fatty acids etc. Key polyphenolic flavonoids such as isorhamnetin and quercetin are believed to be mainly responsible behind its health benefits (against cardiovascular diseases, metabolic syndrome, obesity etc.) through properties including anti-cancer, antioxidant, and anti-inflammatory activities. These sea buckthorn constituents appear to mediate healthy ovarian cell proliferation, death, and hormone release, as well as decrease ovarian cancer possibly through apoptosis, and hormonal (estrogen) release. Thus, sea buckthorn and its bioactive ingredients may have potential in the management of gynecological problems such as uterine inflammation, endometriosis, and easing symptoms of vulvovaginal atrophy in postmenopausal women (by targeting inflammatory cytokines and vascular endothelial growth factor – VEGF). Apigenin, myricetin, and luteolin have also been recommended as prospective ovarian cancer preventative and adjuvant therapy options as they can inhibit ovarian cancerogenesis by triggering apoptosis and halting the cell cycle in ovarian tumors. Furthermore, its oil (containing carotenoid, sterol, and hypericin) has been speculated as an alternative to estrogen replacement therapy for postmenopausal women particularly to improve vaginal epithelial integrity. However, it is uncertain whether steroid hormone receptors, reactive oxygen species (ROS), and inflammatory regulators are actually behind sea buckhorn’s actions. Sea buckthorn, and its compounds’ health promoting potential warrants further validation not just in vitro and in animal research, but also in clinical trials to identify and/or standardize optimal methods of delivery of biologically active molecules. [ABSTRACT FROM AUTHOR]