Search Results (1,855)

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

Background/Objectives: Vitamin D plays a central role in calcium and bone homeostasis; however, evidence linking serum 25-hydroxyvitamin D (25(OH)D) to bone mineral density (BMD) in postmenopausal women remains inconsistent. Because body weight and lean mass strongly influence skeletal loading and may also affect circulating 25(OH)D, we aimed to evaluate the association between serum 25(OH)D and bone outcomes in early postmenopausal women and to determine whether body composition attenuates this relationship. Methods: In this cross-sectional study, 120 women within 10 years after natural menopause (59.5 ± 6.3 years) were assessed. Serum 25(OH)D was measured by chemiluminescent immunoassay. Total body areal bone mineral density (total body aBMD, g/cm²) was assessed by DXA, and trabecular volumetric BMD and cortical thickness were obtained using 3D modeling. Associations were examined using Spearman correlations and multivariable linear and logistic regression models adjusted for age, body weight, lean mass, and years since menopause. Results: Median serum 25(OH)D was 23.7 ng/mL [16.7–30.4]. A modest correlation was observed between 25(OH)D and total body aBMD (ρ = 0.22, p = 0.016), but not with trabecular volumetric BMD or cortical thickness. After adjustment, 25(OH)D was not independently associated with total body aBMD (p = 0.144), whereas body weight remained significantly associated (β = 0.27, p = 0.002). In logistic models, body weight (OR = 0.93, 95% CI 0.90–0.96) and lean mass (OR = 0.97, 95% CI 0.95–0.99) were protective against low BMD, while the association with 25(OH)D was modest. Conclusions: In early postmenopause, the association between serum 25(OH)D and BMD is modest and largely attenuated after accounting for body composition. Body weight and lean mass appear to be stronger determinants of bone outcomes than vitamin D status. Full article

Background: Low estrogen levels during menopause reduce nitric oxide (NO) production, contributing to decline in skeletal muscle quality and function. Although acute and short-term dietary nitrate supplementation has demonstrated promising effects, long-term benefits, particularly on muscle quality in postmenopausal women, are not well established. Objectives: The objective was to investigate the effects of long-term (12-week) nitrate-rich beetroot extract supplementation on morphological and functional muscle quality, rate of force development (RFD), maximal strength, and circulating nitrate/nitrite concentrations in postmenopausal women. Methods: In a randomized, double-blind, placebo-controlled design, 20 postmenopausal women (21 years ± 7 since menopause) consumed 20 g/day of a nitrate-rich beetroot extract (BET; 548 mg nitrate/day) or a nitrate-depleted beetroot extract (PLA; 43 mg nitrate/day) for 12 weeks. Outcome measures, including muscle quality (functional via muscle strength/thickness ratio; morphological via ultrasound echo intensity), RFD, maximal voluntary isometric contraction (MVIC), and serum nitrate/nitrite levels, were evaluated at baseline, 8 weeks, and 12 weeks. Results: BET significantly increased serum nitrate (0.005) and nitrite (0.022) levels compared to PLA at both week 8 and week 12. Morphological muscle quality also improved significantly in the BET group (interaction effect, p = 0.014). Early-phase rate of force development (RFD) increased between 30 and 100 ms, whereas late-phase RFD increased between 100 and 200 ms. RFD_peak also improved by week 8, and these gains were maintained through week 12 (interaction effect, p < 0.05). Although there was no significant difference between groups for functional muscle quality, MVIC increased at week 12 in the BET group, but no significant Time × Group interaction was observed. Conclusions: Twelve weeks of nitrate-rich beetroot extract supplementation improved morphological muscle quality and RFD, suggesting potential clinical relevance for preventing structural and neuromuscular function decline in postmenopausal women. This study was registered with ReBEC (RBR-87qh649) and approved on 8 October 2024. Full article

This narrative review aims to analyze sex-specific differences in oral health, examine hormonal influences in women during puberty, pregnancy, and menopause, and compare oral health behaviors between men and women. Articles were selected based on: (1) sex-specific aspects of oral diseases, (2) hormonal influences on oral health, (3) comparative analyses between sexes, and (4) sex-disaggregated data on oral disease prevalence. Women experience hormonal vulnerabilities with estrogen deficiency causing xerostomia, mucosal atrophy, and increased caries susceptibility, showing parallels between oral and vaginal mucosa. Men demonstrate higher periodontitis prevalence (57% vs. 38%), utilize preventive services one-third less frequently, and show higher smoking rates (67% vs. 42%) and traumatic dental injuries (2:1 ratio). Women maintain better oral hygiene and treatment adherence. Sex-specific factors affecting both sexes remain unconsidered in dental practice. Women need targeted interventions during hormonal transitions, while men require improved preventive care engagement. Future research integrating sex-specific considerations is required to enable personalized oral health approaches for both sexes. Full article

The vaginal microbiome (VM), a complex and dynamic microbial ecosystem, is now recognized as a central determinant of female reproductive and gynecologic health. Under homeostatic conditions, a Lactobacillus-dominant ecosystem maintains vaginal acidity, provides colonization resistance, and modulates mucosal immunity. Conversely, vaginal dysbiosis—characterized by Lactobacillus depletion and anaerobic or aerobic overgrowth—is associated with infectious vaginitis, increased susceptibility to sexually transmitted infections, and non-infectious conditions such as genitourinary syndrome of menopause. This review provides an integrated overview of the composition, functional characteristics, and host interactions of the VM across health and disease. We highlight major mechanisms by which microbial dysbiosis contributes to disease pathogenesis, including biofilm formation, altered microbial metabolism, and immune dysregulation. In addition, we discuss the translational potential of the VM as a source of diagnostic and prognostic biomarkers and as a target for emerging microbiome-dependent therapeutic strategies. Collectively, current evidence supports the view that vaginal dysbiosis is a heterogeneous and context-dependent state driven by distinct pathogen- and host-related mechanisms, underscoring the importance of prioritizing microbiome restoration rather than pathogen eradication alone. Full article