Search Results (1,859)

Background/Objectives: Endometrial cancer (EC) is a multifactorial disease influenced by metabolic, hormonal, and environmental factors. Trace and macroelements play a critical role in cellular homeostasis, oxidative stress, and tumor progression; however, their relationship with EC grading and clinical characteristics remains insufficiently understood. Methods: This study evaluated the concentrations of selected macro- and trace elements (Na, K, Ca, P, Mg, Mn, Cu, Zn, Be, As, Cr, Mo, Ti, Tl, Pb) in patients with endometrial cancer (G1–G3) and a control group (C). Elemental analysis was performed using inductively coupled plasma optical emission spectrometry (ICP-OES). Associations between elemental concentrations and clinicopathological variables, including age, body mass index (BMI), menopausal status, diabetes, and smoking, were assessed using appropriate statistical tests, including ANOVA with Tukey’s post hoc analysis and Student’s t-test. Multivariate regression analysis was performed to identify independent predictors of elemental alterations. Results: Significant differences in elemental concentrations were observed across EC grading. Higher-grade tumors were associated with increased levels of Ca, P, Mg, and Mn, while Na and K showed a decreasing trend with tumor progression. No statistically significant differences were observed for Zn, Ti, Tl, or Pb across histological grades. Stratified analyses demonstrated that clinical and metabolic factors had a limited and selective impact on elemental profiles. Age and BMI were associated with minor variations in selected elements, whereas menopausal status, diabetes, and smoking showed predominantly non-significant or inconsistent effects. Multivariate analysis identified histological grade as the primary determinant of elemental alterations, while other variables exhibited weaker or element-specific associations. Conclusions: Elemental homeostasis in endometrial cancer is primarily associated with tumor progression rather than systemic metabolic or lifestyle factors. Changes in Ca-, P-, Mg-, and Mn-related pathways may reflect tumor-driven metabolic reprogramming, whereas most trace elements remain relatively stable. These findings suggest that elemental profiling may provide insight into EC biology, although its clinical utility requires further investigation. Full article

Menopause is a natural biological transition marked by the cessation of regular menstrual cycles and is associated with significant endocrine, hormonal, and metabolic changes. Sleep disturbances are among the most common and distressing symptoms during this period, affecting approximately 40–60% of women in the menopausal transition and postmenopause. Vasomotor symptoms, including hot flushes and night sweats, often occur alongside fatigue, anxiety, and mood disturbances. These symptoms frequently coexist with sleep disorders such as insomnia, early morning awakenings, fragmented sleep, obstructive sleep apnea, restless legs syndrome, and circadian rhythm disruptions. Evidence from animal models, translational research, and clinical studies highlights the complex interaction between hormonal fluctuations, neuroendocrine dysregulation, metabolic changes, and circadian rhythm disruption. These factors contribute to altered sleep regulation, appetite control, and weight gain during the menopausal transition. This review summarizes current evidence on the mechanisms of underlying sleep disturbances in menopause, their clinical manifestations, diagnostic approaches, and available therapeutic strategies. Improving the management of sleep disorders during this stage may substantially enhance overall health and quality of life in menopausal women. We discuss presentation of different sleep disorders in menopause, their current management and future direction of research for development of precision-based algorithm of treatment considering the endocrine and hormonal profile of the women. Full article

Background: Systemic arterial hypertension (SAH) shows a high prevalence among postmenopausal women and represents an important public health concern. Objective: To evaluate factors associated with SAH in postmenopausal women participating in a resistance training program. Methods: This observational, cross-sectional study included 55 postmenopausal women (66.0 ± 4.9 years) recruited from the “More Active Women” research project, an umbrella experimental and longitudinal study involving resistance training interventions. Cross-sectional data were collected during the baseline assessment (April–May 2025). Sociodemographic variables, nutritional status (body mass index and waist circumference), and behavioral and health-related variables obtained through structured interviews and anthropometric assessments were analyzed. Associations were tested using Pearson’s chi-square test or Fisher’s exact test, with effect size estimated by Phi or Cramer’s V when appropriate, and binary logistic regression was performed for adjusted analyses. Results: Significant associations were observed between SAH and elevated BMI (p = 0.03; φ = 0.30), waist circumference > 88 cm (p = 0.006; φ = 0.40), and lower educational level (p = 0.003; V = 0.47). In the adjusted analysis, waist circumference ≤ 88 cm was associated with a lower likelihood of SAH (OR = 5.54; 95% CI: 0.965–31.872; p = 0.007), whereas lower educational level was associated with a higher likelihood of hypertension (OR = 13.98; 95% CI: 1.505–129.833; p = 0.004). Conclusion: Excess central adiposity and lower educational level are associated with SAH in postmenopausal women, highlighting the importance of integrated health promotion strategies that address both cardiometabolic risk factors and social determinants of health during aging. Full article

Background: Menopausal symptoms can negatively affect health-related quality of life (HRQoL), especially in women with a history of cancer. This study compared menopause-specific HRQoL in peri- and postmenopausal women with and without cancer and explored differences by cancer type, menopause treatment use, and depression. Methods: We performed a cross-sectional multicenter study using self-reported data from 6833 women enrolled through the Mi Menopausia mobile app between 2021 and 2024. HRQoL was assessed with the Cervantes SF-16 scale. Results: The final sample consisted of 6833 women: no cancer (n = 6482) and cancer (n = 351), further classified as gynecologic (n = 210) and non-gynecologic (n = 141). Cancer history was associated with worse HRQoL in the Sexuality domain (51.2 ± 23.8 vs. 48.3 ± 24.6; p = 0.013), while global HRQoL did not differ significantly between women with and without cancer (30.6 ± 21.7 vs. 32.3 ± 20.7; p = 0.130). Among cancer women, Sexuality scores were worse in non-gynecologic versus gynecologic cancers (55.7 ± 22.9 vs. 48.2 ± 24.1; p = 0.005). Depression was consistently associated with worse HRQoL in all groups, while menopause treatment use was associated with poorer HRQoL only in women without cancer. Conclusions: Cancer history was mainly associated with poorer sexual menopause-related HRQoL rather than global HRQoL. Depression was a major factor linked to impaired HRQoL, highlighting the need for integrated sexual and mental health assessment in menopausal women, particularly cancer survivors. Full article

Background/Objectives: Ultra-processed food (UPF) consumption is increasing worldwide, yet its domain-specific impact on health-related quality of life (HRQoL) among postmenopausal women remains poorly characterized. This study investigated associations between UPF intake and domain-specific and overall HRQoL in a nationally representative sample of Korean postmenopausal women. Methods: Data from the Korea National Health and Nutrition Examination Survey (2013–2021) were analyzed. UPF consumption was assessed using a single 24 h dietary recall and classified according to the NOVA food classification system. HRQoL was evaluated using the five EQ-5D domains and the overall EQ-5D index. Survey-weighted logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) across UPF intake quartiles, adjusting for socioeconomic and health-related covariates. Results: Higher UPF consumption was associated with impairments in specific HRQoL domains rather than a uniform decline across domains. In fully adjusted models, women in the third UPF intake quartile had higher odds of mobility impairment (OR 1.74; 95% CI 1.06–2.86) and anxiety/depression symptoms (OR 1.71; 95% CI 1.06–2.77) than those in the lowest quartile. A significant linear trend was observed for mobility (P-for-trend = 0.012). In contrast, associations with the overall EQ-5D index score were limited and not consistently observed after full adjustment. Conclusions: Higher UPF consumption is associated with domain-specific HRQoL impairments, particularly affecting physical mobility and mental health, among postmenopausal women. These findings underscore the importance of domain-specific assessments and suggest that UPF consumption may be related to certain aspects of functional and psychological well-being after menopause. Full article

Background/Objectives: Bone is the most common organ affected by distant metastasis in advanced breast cancer, and the development of skeletal-related events (SREs) often leads to significant deterioration in patients’ quality of life and survival outcomes. In this study, we aimed to explore the risk factors associated with bone metastasis in breast cancer and to develop a predictive nomogram for identifying high-risk patients, which may facilitate timely preventive interventions and improve clinical prognosis. Methods: A retrospective analysis was conducted on 672 patients with breast cancer who underwent surgery at the Fourth Hospital of Hebei Medical University (Shijiazhuang, China) between 2013 and 2023; this cohort served as the training set. Clinical and pathological characteristics potentially influencing bone metastasis—including age, menopausal status, histological grade, affected side, maximum tumor diameter, lymph node staging, TNM staging, ER status, PR status, HER-2 status, Ki-67, molecular subtypes, vascular tumor thrombus, nerve infiltration and visceral metastasis—were collected. The median follow-up time was 42 months. Patients were stratified into two cohorts based on whether postoperative bone metastasis occurred, with groups matched according to Tumor–Node–Metastasis (TNM) stage. Univariate and multivariate logistic regression models were applied to identify independent factors associated with breast cancer bone metastasis, and a nomogram prediction model was constructed using the variables retained in the final analysis. For external validation, data from 2814 patients with breast cancer who underwent surgery between 2013 and 2021 were extracted from the U.S. Surveillance, Epidemiology, and End Results database. Results: The multivariate logistic regression analysis revealed that histological grade (p = 0.002), progesterone receptor (PR) negativity (p = 0.001), human epidermal growth factor receptor 2 (HER-2) negativity (p = 0.002) and visceral metastasis (p < 0.001) were identified as independent predictors of bone metastasis in breast cancer. A nomogram predictive model was established using these four factors. The area under the receiver operating characteristic curve was 0.720 (95% confidence interval (CI): 0.6797–0.7607) for the training cohort and 0.701 (95% CI: 0.6813–0.7205) for the external validation cohort. Decision curve analysis further confirmed the clinical applicability of the model. Conclusions: The present study confirms that histological grade, PR status, HER-2 status and visceral metastasis are independent factors associated with bone metastasis in breast cancer. The constructed nomogram may effectively predict breast cancer-related bone metastasis and could serve as a practical tool for clinical decision-making. Full article

TFF1 is a secretory polypeptide that is typical of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. Originally, TFF1 was discovered as an estrogen-responsive gene in breast cancer cell lines. However, its major physiological expression site is the stomach where it exists mainly in a monomeric form, with minor amounts of homodimeric as well as heterodimeric forms, such as a high-molecular-mass complex with IgG Fc binding protein (FCGBP). For the first time, we characterized different low-molecular-mass forms of TFF1 in human post-menopausal vaginal specimens, i.e., monomeric and dimeric forms. Attempts to identify high-molecular-mass forms of TFF1, such as TFF1-FCGBP, failed. Based on its known anti-inflammatory effects, TFF1 could play an important role in the homeostasis of vaginal microbiota, which is normally predominated by Lactobacillus spp. Due to its lectin activity, TFF1 might also be capable of binding to members of the vaginal microbiota or to vaginal fungal pathogens. This points to a potential role for TFF1 in the vagina’s innate immune defence and could be of clinical relevance particularly after menopause, e.g., for the treatment of bacterial vaginosis or vulvovaginal candidiasis, as here vaginal dysbiosis is often observed as a consequence of estrogen deficiency. Full article

Background: Cervical cancer remains a major global health burden, with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) representing the two predominant histological subtypes. Comparative clinicopathological patterns between SCC and ADC in contemporary cohorts remain of interest, but inference is often limited by small single-center datasets. Methods: We conducted a retrospective single-center cohort analysis of cervical cancer patients treated between 2020 and 2024. Demographic, clinical, and pathological variables, including p16 immunohistochemistry, histological subtype, differentiation grade, FIGO stage, and survival status, were analyzed. Comparative analyses were performed using appropriate exact tests, and survival was assessed using Kaplan–Meier methods. Results: The cohort included 85 patients: 69 with squamous cell carcinoma and 16 with adenocarcinoma. Both subtypes demonstrated similarly high p16 positive rates (89.9% vs. 93.8%, p = 1.00). Menopausal status emerged as a distinguishing factor (p = 0.0047), with SCC patients more likely to be postmenopausal. SCC patients were older on average (52.16 vs. 48.2 years: p = 0.0131). Analyses involving p16 status were interpreted descriptively due to the very small number of p16-negative cases. Kaplan–Meier analysis revealed significant survival differences by clinical stage (log-rank p = 0.03), with high-stage patients showing progressive decline from 95% to 73% survival over five years, while low-stage patients maintained 100% survival. Conclusions: In this retrospective single-center cohort, SCC and ADC showed similar p16 positivity rates and clinical stage remained the most informative prognostic variable. Apparent subtype-related demographic differences and multivariable associations should be considered hypothesis-generating rather than definitive. Larger multicenter studies with standardized pathology and p16 assessment, direct HPV testing/genotyping, and more complete clinical and prevention-related data are needed before prognostic or clinical conclusions are drawn. Full article

The loss of estrogen following menopause is associated with a marked increase in cardiometabolic risk, accompanied by adverse changes in lipid metabolism, insulin sensitivity, vascular function, and systemic inflammatory tone. Emerging evidence suggests that estrogen signaling interacts with chromatin regulatory mechanisms, including DNA methylation, histone modifications, and chromatin remodeling, across multiple metabolic tissues. In this review, we examine current evidence linking estrogen receptor signaling to epigenetic modulation in cardiovascular, hepatic, adipose, vascular, and immune systems. We propose that epigenetic remodeling represents a plausible and testable mechanistic framework connecting estrogen depletion to cardiometabolic disease progression, while acknowledging that much of the mechanistic evidence derives from preclinical and in vitro systems and that direct longitudinal validation in human cardiovascular tissues remains limited. We further explore how this framework may contribute to understanding the “estrogen paradox” and the heterogeneous outcomes of hormone replacement therapy (HRT), particularly within the context of the timing hypothesis. Finally, we evaluate pharmacologic and lifestyle interventions, including structured exercise, dietary modulation, and cardiometabolic therapeutics, through the lens of potential epigenetic influence. Clarifying tissue-specific and immune-integrated chromatin responses to estrogen loss will be essential for advancing precision strategies aimed at improving cardiometabolic health in postmenopausal women. Full article

Background/Objectives: EndoPredict is a second-generation prognostic assay for estrogen-receptor-positive, HER2-negative breast cancer that integrates molecular and clinical parameters for risk stratification. Multiple studies have reported its clinical utility, while differences in the proportion of patients classified as high- or low-risk have been observed across cohorts. This study aimed to characterize clinical, pathological, and demographic factors associated with these differences. Methods: We conducted a descriptive review of 17 published studies and analyzed a single-institution cohort of 140 patients. Associations between clinicopathological variables and high-risk classification were assessed, including tumor size, lymph node status, histological grade, Ki-67 expression, and reproductive and demographic factors. Differences in inclusion criteria and cohort characteristics were also examined. Results: Tumor size and lymph node involvement emerged as primary determinants of high-risk classification. A high histological grade and Ki-67 levels above 25% were significantly associated with high-risk status (p < 0.001). Conversely, age, age at menarche, menopausal status, Body Mass Index, progesterone receptor expression, molecular subtype, and histological type showed no significant association. A higher number of pregnancies correlated with a lower frequency of high-risk classification (p < 0.01). Heterogeneity in risk distribution across studies was largely attributable to differences in tumor size, nodal involvement, and histological grade. Additional variability was associated with inclusion criteria, sample selection, and regional demographic characteristics. Conclusions: Variability in EndoPredict risk classification reflects both tumor biological features and population-specific factors. These findings emphasize the importance of interpreting genomic risk scores within their clinical and demographic context and support the comparison of risk distributions across heterogeneous patient cohorts. Full article

Background and Objectives: Genitourinary syndrome of menopause (GSM), previously known as vulvovaginal atrophy, is a chronic, progressive hypoestrogenic condition affecting vulvovaginal, urinary and sexual health in women. Common symptoms include vaginal dryness, itching, dyspareunia, urinary urgency and recurrent urinary tract infections (UTIs). Despite the high prevalence, GSM is underdiagnosed and undertreated, thereby negatively impacting women’s quality of life. To illustrate the practical aspects of GSM diagnosis and provide evidence-based management, we present a case-based narrative review synthesizing recently published, high-quality evidence. Materials and Methods: Evidence was drawn from multiple sources through targeted searches of databases, and included the 2025 AUA/SUFU/AUGS guideline (AUA), the 2024 NICE network meta-analyses (NICE), a 2025 systematic review/meta-analysis in breast-cancer survivors, the 2020 Menopause Society GSM Position Statement, the 2018 NAMS/ISSWSH breast cancer consensus, several primary source citations and other high quality peer-reviewed publications. Results: Five illustrative composite case vignettes of GSM are presented to highlight the evaluation strategy and evidence-supported treatment choices. Nonhormonal options are the first line treatments for mild GSM symptoms, either with or without the addition of vaginal estrogen therapy. For moderate to severe GSM, low-dose vaginal estrogen, vaginal DHEA, and ospemifene are all effective FDA-approved options. In breast cancer survivors, individualized decisions with oncology input are warranted. Maximal caution and a shared decision-making approach is required for women using Aromatase Inhibitors (AIs) for breast cancer risk reduction when choosing treatments for GSM. Conclusions: Treating GSM improves vaginal, sexual and urinary outcomes and quality of life of women. Clinicians need to proactively screen for GSM and offer evidence-based treatment options. The treatment decisions in breast cancer survivors are nuanced, requiring a shared-decision approach. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is now widely identified as a multisystem disorder with oncogenic implications that extend beyond liver-specific outcomes. Nonetheless, the link between MASLD and gynecologic cancers remains insufficiently characterized in robust, well-powered population studies. We investigated this association by menopausal status in a large cohort of Korean women. Methods: We performed a longitudinal cohort study utilizing data from a nationwide Korean cohort of over 2 million women, with a median observation period of 12.3 years. MASLD, including its subtypes metabolic alcohol-associated liver disease (MetALD), and alcohol-related liver disease (ALD) with metabolic dysfunction were identified using the most recent diagnostic standards. Adjusted hazard ratios (aHR) for gynecologic cancers were estimated with Cox models, accounting for metabolic, reproductive, and lifestyle factors. Results: In premenopausal women, MASLD was associated with increased risks of cervical (aHR, 1.13, 95% CI, 1.01–1.26), endometrial (aHR, 1.63, 95% CI, 1.50–1.79) and ovarian cancer (aHR, 1.22, 95% CI, 1.12–1.33). In postmenopausal women, MASLD similarly conferred elevated risks across all three cancers: cervical (aHR, 1.12, 95% CI, 1.05–1.20), endometrial (aHR, 1.42, 95% CI, 1.32–1.54) and ovarian cancer (aHR, 1.14, 95% CI, 1.08–1.20). Conclusions: MASLD should be considered an independent and modifiable risk determinant for gynecologic cancers. These data underscore the necessity of including hepatic steatosis in risk assessment protocols for cancer prevention. Early recognition and directed screening among metabolically susceptible women may provide important avenues for proactive cancer risk reduction. Full article

Inflammation and oxidative stress are key mechanisms in aging, contributing to neurodegenerative diseases, cardiovascular diseases, type 2 diabetes, obesity, and other conditions. In the aging process, the increase in reactive oxygen species and the decrease in antioxidant pathways damage cellular components, accelerating deterioration. Persistent inflammation and oxidative stress also favor the progression of diseases such as atherosclerosis, where LDL oxidation and infiltration in the arteries generate plaques that can lead to myocardial infarction or stroke. In addition, inflammation and oxidative stress can affect the immune system, as well as the development of chronic inflammatory diseases and nonalcoholic fatty liver disease, and may affect mental health, healthy menopause and muscle recovery. Research from both human studies and laboratory tests indicates that taking 80–320 mg per day of anthocyanin-rich extracts from bilberries and blackcurrants (Anthocyanin-EBB) can moderately enhance cholesterol levels, lower markers of inflammation, boost blood vessel health, increase insulin responsiveness, and reduce indicators linked to cardiovascular and metabolic risks. They also have antioxidant, anti-inflammatory and neuroprotective effects, helping in the prevention and management of chronic diseases. As a result, supplementation with anthocyanin-rich extracts may be a promising strategy to promote healthy aging and reduce the risk of development and progression of conditions related to oxidative stress and chronic inflammation. Nevertheless, due to the limited patient populations and short follow-up periods in most existing studies, long-term clinical trials are necessary to determine the definitive advantages of Anthocyanin-EBB in clinical practice. Full article

Polyphenols represent the largest and most diverse class of dietary antioxidants. Epidemiological evidence linking specific (poly)phenol classes, such as flavonoids and lignans, to breast cancer (BC) risk remains limited and largely inconclusive in prospective studies. The aim of this study is to examine the association between the intake of total (poly)phenols—and its classes and subclasses—and BC risk—overall and by subtypes (estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2))—in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The EPIC cohort includes 257,960 adult women from seven European countries. During a mean follow-up of 14 years, there were 10,722 incident overall BC cases. Associations were computed using Cox regression models adjusted for potential confounders. No significant associations were found between total (poly)phenol intake and overall BC risk (HR_{Q5 vs. Q1} = 1.02; 95% CI: 0.95–1.11). In addition, null associations were mostly found between classes and subclasses of (poly)phenols and BC subtypes. After stratifying by menopausal status, no significant associations were observed. In conclusion, this study found no evidence of associations between the intake of any class or subclass of (poly)phenols and BC risk in the European population. Full article

Background/Objectives: Migraine is a leading cause of disability in women and is intricately linked to hormonal fluctuations and systemic health. This review aims to unravel the complex relationship between migraine, cardiovascular disease, and metabolic syndrome throughout the female reproductive lifespan. Methods: A comprehensive narrative review was conducted using the PubMed database for studies published between January 1988 and December 2025. Keywords included “migraine”, “cardiovascular risk”, “metabolic syndrome”, “pregnancy”, and “hormonal therapy”. Articles were selected to synthesize the latest pathophysiological evidence and clinical guidelines. Results: Migraine prevalence in women is two to threefold higher than in men, peaking during fertile age. Hormonal milestones, particularly estrogen withdrawal, trigger menstrual migraine. Metabolic syndrome is significantly more common in migraineurs than the general population. Obesity and insulin resistance have been associated with higher migraine attack frequency and severity. Experimental evidence suggests that hyperinsulinemia may sensitize TRPV1 receptors on trigeminal neurons and enhance CGRP release, potentially lowering the activation threshold for migraine attacks; however, direct confirmation of this pathway in humans remains limited. Furthermore, migraine with aura is linked to a doubled risk of ischemic stroke and increased risk of cardiovascular events. In pregnancy, migraine is an independent risk factor for stroke, myocardial infarction, and spontaneous coronary artery dissection. Conclusions: Migraine is a critical marker for cardiovascular and metabolic risk, necessitating routine screening and multidisciplinary management. Clinicians must prioritize cardiovascular counselling, metabolic evaluations, and careful monitoring in these patients, especially during pregnancy. Hormonal therapy choices should be individualized, preferring progestin-only contraceptives for those with aura and transdermal routes for hormone replacement therapy to minimize cardiometabolic impact. Full article