Search Results (4,346)

Objectives: The aim of this study was to review the importance of peritoneal fluid steroid hormone concentrations to understand the mechanism of hormonal medical treatment of endometriosis-associated pain. Design: The study included a PubMed search and a pilot trial in 8 adolescents. Results: Oral contraceptives (OCs) were designed to inhibit ovulation in all women, and doses are much higher than the mean ovulation-inhibiting dose. Therefore, in most women, half a dose and in some women, even less is sufficient to inhibit ovulation. The inhibition of ovarian function and ovulation decreases estrogen and progesterone concentrations in plasma and peritoneal fluid. Surprisingly, the effect on peritoneal fluid steroid hormone concentrations has not been considered to explain the impact on endometriosis-associated pain. The lowering of the high estrogen concentrations in peritoneal fluid is sufficient to explain the pain decrease in superficial and ovarian endometriosis. A direct progesterone effect is unlikely, given the high progesterone concentrations in the peritoneal fluid of ovulatory women. In 8 adolescents, half an OC dose resulted in an apparently similar pain relief as a full dose (personal observation). Conclusions: The decrease in ovarian and superficial pelvic endometriosis-associated pain with OCs can be explained by lowering the intra-ovarian and the high estrogen concentrations in peritoneal fluid after ovulation. A direct progesterone effect is unlikely. Since OCs are severely overdosed in most women, half a dose is sufficient in most with fewer side effects, permitting individualization of therapy in women not requiring contraception. Understanding peritoneal fluid also explains that hormone replacement therapy is not contraindicated in most women with a history of endometriosis. Since the mechanisms of medical therapy of endometriosis-associated pain and the prevention of progression might be different, the growth of lesions must be monitored during treatment. Full article

Polycystic ovary syndrome (PCOS) is a systemic metabolic and endocrine disorder that significantly disrupts reproductive physiology and endometrial function. In this narrative review, we examine the molecular impact of metabolic and hormonal imbalances on the endometrium of women with PCOS. We investigate the specific mechanisms that delineate how hyperinsulinemia and insulin resistance, chronic low-grade inflammation, and estrogen/progesterone/androgen imbalance contribute to altered epigenetic, transcriptomic, metabolomic, and signaling profiles in a wide array of different cell types within endometrial tissues. The synergistic interplay between upregulated inflammatory cytokines (e.g., IL-1,2,6,8,17,18, and TNF-α), along with key changes in critical molecular pathways associated with hyperinsulinemia and insulin resistance (e.g., PI3K/AKT/MAPK, and Wnt/β-catenin), in addition to aberrant sex steroid hormone signaling (e.g., CYP19A1, COX-2, PGE₂, HOXA10, 11βHSD2), promotes deleterious changes within the endometrial microenvironment. These anomalies underpin a spectrum of clinical manifestations observed in women with PCOS at each stage of the life course, including abnormal uterine bleeding in reproductive-age women, impaired decidualization in pregnancy, and altered postmenopausal endometrial physiology. Clinically, these alterations are associated with abnormal uterine bleeding, subfertility, implantation failure, miscarriage, pregnancy complications, and postmenopausal endometrial hyperplasia and cancer. Overall, our review provides novel insights into the molecular mechanisms linking systemic metabolic and endocrine dysfunction with endometrial pathology in PCOS and has broader implications that apply to all women. Full article

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that affects women more frequently than men. This sex gap has widened over the past century, and appears to be shaped by lifestyle factors more than biological factors. This narrative review examines the evidence for sex-specific differences in lifestyle risk factors and their impact on both MS susceptibility and disease progression, with implications for diagnosis, monitoring, and treatment. Smoking, obesity, vitamin D deficiency, ultraviolet radiation exposure, and Epstein–Barr virus infection all interact with sex-related biological pathways to influence MS risk. Women appear to be more vulnerable to the pathogenic effects of smoking and obesity, both independently and in synergy with genetic risk alleles, while vitamin D and UV exposure confer stronger protective effects in females than in males. EBV infection also exhibits sex-dependent immune responses, shaped by hormonal regulation and host–virus genetic interactions. Sex-related lifestyle factors also modulate MS progression. Women experience more inflammatory activity and relapses, whereas men more often develop a progressive phenotype with greater neurodegeneration. Hormonal changes during female reproductive phases, such as pregnancy, breastfeeding, menopause, and hormone-based therapies, critically influence disease activity and progression in MS. Obesity, smoking, vitamin D status, diet, and gut microbiota further interact with sex hormones and genetic background, contributing to variable disease trajectories, also modulated by social determinants such as education level. These findings underscore the need to integrate into clinical practice the evaluation of lifestyle factors in a sex-specific way for diagnosis, monitoring, and treatment of MS. Full article

Hormone replacement therapy (HRT) has been utilized in clinical practice for decades as a main therapeutic approach for mitigating menopausal symptoms. The symptoms mostly encompass vasomotor and genitourinary issues resulting from the deficiency of estrogen and progesterone. Initially identified as a universally advantageous and indispensable intervention, hormone replacement therapy subsequently became the subject of considerable scientific and clinical debate, especially after the publication of extensive epidemiological studies indicating potential adverse effects associated with cardiovascular and cancer risk. This study aims to reassess the role of HRT in clinical practice by analyzing its historical evolution, expanded clinical uses, and changes in guidelines necessitated by resent scientific studies. Current evidence from clinical studies and meta-analyses unequivocally demonstrates that hormone replacement therapy is the most efficacious treatment for vasomotor and urogenital symptoms, and also acknowledging its potential role in osteoporosis prevention. The administration of HRT requires careful individual assessment, considering the patient’s age, timing of initiation, existence of comorbidities. In this setting, therapy decisions have to be based on a combination of the most up-to-date clinical guidelines, risk stratification, and the patient’s preferences. In conclusion, the assessment of HRT confirms its primary role in reducing menopausal symptoms while also highlighting the imperative for a individual strategy that balances benefits and risks to improve outcomes for women. Full article

Endocrine disruptors contaminate indoor and outdoor air, water, and food. Besides modifications of the androgen/estrogen balance, endocrine disruptors can alter thyroid function, metabolic balance, immune defenses, and brain development during fetal life, childhood, and adolescence. Among the consequences of fetal exposure to endocrine disruptors, neurobehavioral disorders, particularly psychiatric disorders (for example, schizophrenia and bipolar disorder), attention deficit disorders, and mood disorders, occupy a special place. Therefore, endocrine disruptors are also neuroendocrine disruptors. This review article first summarizes the direct and transgenerational effects of endocrine disruptors. Then, data from a French national cohort of patients whose mothers were treated with synthetic hormones (estrogens and/or progestogens) during their pregnancy(ies) are used to describe the psychiatric disorders developed by children exposed in utero and the multigenerational and potentially transgenerational impacts. Full article

Atrial fibrillation (AF) is the supraventricular tachy-arrhythmia most commonly detected in the general population, with significant sex-related differences in epidemiology, pathophysiology, and treatment outcomes. Emerging evidence highlights the role of sex hormones—particularly estrogen and testosterone—in modulating left atrial electrophysiologic substrate, structural remodeling, inflammation, and thromboembolic risk. Hormonal fluctuations across different lifespan influence AF onset, progression, and therapeutic response, yet current management approaches largely overlook such determinants. This narrative review integrates data from basic, translational, and clinical research to examine hormonal effects on atrial substrate, disease progression, and differential results of treatments, including stroke prevention, pharmacological options, and transcatheter ablation. It also explores the potential of hormone-targeted interventions, antifibrotic therapies, and precision strategies tailored to hormonal status. Addressing these mechanisms could optimize patient-specific management, improve outcomes and guide future clinical practice recommendations. Advancing toward sex-specific, hormone-informed AF care requires further mechanistic studies, hormonal profiling, and sex-stratified clinical trials. Full article

Bisphenol A (BPA) and its substitutes have been identified as endocrine-disrupting chemicals (EDCs). However, little information is available on their reproductive endocrine disruptive effects in mollusks. This study cloned the full-length sequence (2434 bp) of the estrogen-related receptor (ERR) gene in the freshwater bivalve Corbicula fluminea and performed a bioinformatics analysis and tissue-specific expression analysis. We further examined the expression of the CfERR gene after exposure to E2, BPA, and their substitutes (BPS, BPF, and BPAF) at 1, 10, and 100 μg/L for 0, 1, 7, 14, 21, and 28 days. The results showed that CfERR is a nuclear protein with a typical structure. Phylogenetic analysis indicated a high degree of similarity among bivalve species. The high expression of CfERR in the gonad suggested its important role in reproductive regulation. The exposure experiment confirmed that CfERR showed a time- and dose-dependent upregulation in response to all pollutants, with BPS and BPAF exhibiting stronger estrogenic interference effects. This study facilitates a better understanding of the reproductive regulation of bivalves and provides data to support the toxicity evaluation of BPA and its substitutes. Full article

Nutritional factors play a crucial role in many gynecological disorders, particularly those influenced by estrogen. Uterine fibroids are benign tumors that affect a large proportion of women of reproductive age, especially between 30 and 40 years. These lesions may cause significant symptoms, including pelvic pain, heavy menstrual bleeding, and infertility. In younger women, the onset of fibroids is often associated with familial and genetic predisposition, whereas in adulthood, hormonal influences linked to environmental factors and states of exogenous or endogenous hyperestrogenism are more frequently observed. In both contexts, supportive management through an appropriate diet may provide clinical benefit. Although the precise pathogenesis remains incompletely understood, hormonal, genetic, and environmental components—particularly hyperestrogenism—are considered key contributors to fibroid development. Current evidence suggests that consumption of saturated fats, particularly from red meat and full-fat dairy, may raise circulating estrogen concentrations and contribute to the development of fibroids. In contrast, diets abundant in fiber, fruits, and vegetables appear to exert a protective effect, potentially lowering fibroid risk. Obesity, through increased aromatization and consequent estrogen production, also represents an established risk factor. This narrative review aims to explore the role of nutritional determinants in the onset and progression of uterine fibroids, with a specific focus on the impact of individual nutrients, foods, and dietary patterns on clinical outcomes. Particular emphasis is placed on obesity and macronutrient composition (e.g., high-fat versus high-fiber dietary regimens) as potential modulators of circulating estrogen levels and, consequently, fibroid growth dynamics. Furthermore, the potential of nutritional strategies as complementary therapeutic approaches, capable of integrating established clinical practices, is examined. Full article

Background and Objectives: To evaluate the prognostic value of the Clinical–Pathologic Stage–Estrogen receptor status and Grade (CPS+EG) staging system, which combines clinical staging, pathological staging, oestrogen receptor (ER) status, and tumour grade in predicting survival outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy (NACT). Materials and Methods: A retrospective review was performed on 245 female breast cancer patients who received anti-HER2 therapy alongside NACT at the Medical Oncology Department of Kartal Dr Lütfi Kırdar City Hospital, University of Health Sciences, from April 2012 to June 2024. The CPS+EG score was calculated using the MD Anderson Cancer Centre neoadjuvant treatment response calculator. Patients were categorised into two groups based on their CPS+EG score < 3 and ≥3. The primary outcomes assessed were disease-free survival (DFS) and overall survival (OS). Kaplan–Meier and log-rank tests were utilised for time-to-event analysis; Cox regression was used for multivariate analysis. A significance level of ≤0.05 was considered. Results: The median age of the patient cohort was 51 years (range: 27–82 years). Among these patients, 183 (74.6%) had a CPS+EG score less than 3, while 62 (25.3%) exhibited a score of 3 or higher. The median follow-up duration was 37.6 months. The pathological complete response (pCR) rate across the entire cohort was 51.8%. Specifically, the pCR rate was 56.3% in the group with CPS+EG scores below 3, and 38.7% in those with scores of 3 or higher (p = 0.017). Patients with CPS+EG scores less than 3 demonstrated superior overall survival (OS), which reached statistical significance in univariate analysis. Multivariate analysis identified the CPS+EG score as an independent prognostic factor for both overall survival and disease-free survival (DFS), with hazard ratios of 0.048 (95% CI: 0.004–0.577, p = 0.017) and 0.35 (95% CI: 0.14–0.86, p = 0.023), respectively. Conclusions: The CPS+EG score is an independent and practical prognostic marker, particularly for overall survival, in patients with HER2-positive breast cancer who have received neoadjuvant therapy. Patients with a CPS+EG score < 3 have higher pCR rates and survival rates. When used in conjunction with pCR, it can improve risk categorisation and contribute to the individualisation of adjuvant strategies in the post-neoadjuvant period. Due to its ease of calculation and lack of additional costs, this score can be instrumental in clinical practice for identifying high-risk patients. Our findings support the integration of the CPS+EG score into routine clinical decision-making processes, although prospective validation studies are necessary. Full article

Schizophrenia is a prevailing yet severely debilitating psychiatric disorder characterized by a convoluted etiology. Although antipsychotics have been available for over half a century, they primarily mitigate symptoms rather than providing definitive care. This limitation suggests that the neurotransmitter systems targeted by these medications are not the root cause of the disorder. Ongoing research seeks to elucidate the cellular, molecular, and circuitry pathways that contribute to the development of schizophrenia. Unfortunately, its precise pathogenesis remains incompletely understood. Accumulating evidence implicates dysregulated neurogenesis and aberrant neurodevelopmental processes as key contributors to disease progression. Recent advances in proteomics and imaging technology have facilitated the emergence of novel models of schizophrenia, emphasizing the roles of neuroinflammation, sex steroids, and cortisol. This paper aims to organize and map the intercorrelations and potential causal effects between various mechanistic models to gain deeper insight on how these mechanisms contribute to the cause, risks, and symptoms of the disorder. Furthermore, we discuss the potential therapeutic strategies that target these pathological pathways. Elucidating these mechanisms may ultimately advance our understanding of schizophrenia’s etiological foundations and guide the development of curative interventions. Full article

Breast cancer remains a leading cause of global mortality. According to international cancer data, significant progress has been made in treating breast cancer; however, metastasis and drug resistance continue to be the primary causes of mortality for many patients. This study investigated the modulation of apoptosis-related genes in response to ionizing radiation and estrogen exposure based on a human breast epithelial cell model (MCF-10F and its transformed variants: Estrogen, Alpha3, Alpha5, Tumor2) previously established, where cells were treated with high linear energy transfer alpha particles, with or without 17β-estradiol. Gene expression profiling was performed using an Affymetrix U133A microarray, and bioinformatic analyses assessed differential expression, estrogen receptor status, and correlations with overall survival. Distinct gene expression patterns emerged across cell lines and tumor subtypes. TP53 expression correlated positively with TP63, BIK, CFLAR, BIRC3, and BCLAF1. TP63, PERP, CFLAR, BCLAF1, GULP1, and BIRC3 were elevated in normal tissue, whereas BIK, PHLDA2, and BBC3 were upregulated in tumors. ER-positive tumors exhibited higher TP63, BIK, BCLAF1, and BBC3 expression, while ER-negative tumors showed increased PERP, CFLAR, BIRC3, and PHLDA2. Notably, elevated BCLAF1 expression was associated with poorer survival in Luminal A patients, and high PHLDA2 expression correlated with reduced survival in Luminal B cases. These findings indicate that resistance to apoptosis is a fundamental mechanism in breast cancer progression and therapeutic evasion. Breast tumors selectively alter the expression of key genes to promote growth, evade apoptosis, and develop therapeutic resistance. The differential expression and correlations of these apoptosis-related genes highlight their potential as molecular targets for future personalized cancer therapies and as valuable biomarkers for prognostic stratification and predicting therapeutic response. Full article

This study systematically analyzed the multidimensional effects of Lactobacillus fermentation on Pueraria lobata (PL) and investigated the potential mechanisms underlying its hypolipidemic activity. Results indicated that fermentation significantly increased the total acid content from 1.02 to 3.48 g·L⁻¹, representing a 2.41-fold increase. Although slight reductions were observed in total flavonoids (8.67%) and total phenolics (6.72%), the majority of bioactive components were well preserved. Other antioxidant capacities were retained at >74.71% of baseline, except hydroxyl radical scavenging. Flavor profiling showed increased sourness and astringency, accompanied by reduced bitterness, with volatile compounds such as β-pinene and trans-2-hexenyl butyrate contributing to a distinct aromatic profile. Untargeted metabolomics analysis revealed that fermentation specifically enhanced the abundance of low-concentration isoflavone aglycones, including daidzein and genistein, suggesting a compositional shift that may improve hypolipidemic efficacy. Integrated network pharmacology and computational modeling predicted that eight key components, including genistein, could stably bind to ten core targets (e.g., AKT1 and MMP9) primarily through hydrogen bonding and hydrophobic interactions, potentially regulating lipid metabolism via the PI3K-AKT, PPAR, and estrogen signaling pathways. This study reveals the role of Lactobacillus fermentation in promoting the conversion of isoflavone glycosides to aglycones in PL and constructs a multi-dimensional “components-targets-pathways-disease” network, providing both experimental evidence and a theoretical foundation for further research on the lipid-lowering mechanisms of fermented PL and the development of related functional products. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder affecting men more frequently than women, a difference that might be due to many factors, including sexual hormones. Estrogens seem to confer a protective effect on the nigrostriatal pathway in experimental studies but their effects on cognition in patients with PD are unknown. Aim: To investigate the impact of the exogenous and endogenous estrogens on cognitive impairment in women with PD. Methods and materials: We recruited and consecutively interviewed outpatient women affected by PD. Each patient underwent a cognitive assessment via the Montreal Cognitive Assessment scale (MoCA), an anamnestic collection of the reproductive lifespan variables and clinical features. We investigated if some of the reproductive lifespan variables investigated could predict cognition outcomes in post-menopausal women with PD. Results: A total of 90 women with PD were recruited. Women with MoCA ≥ 26 (n = 27) had a lower median age at menarche (11 [11,12] vs. 13 [12–14], p < 0.0001), lower disease duration in years (8.3 [6.1–12.7] vs. 9.4 [6–12.7], p = 0.6), and less advanced disease (1 [1,2] vs. 2 [1–3], p = 0.02). Among all the reproductive life-span variables, only earlier age at menarche significantly predicted higher scores on MoCA (aOR = 0.5 [0.3–0.8], p = 0.005). No other clinical and reproductive factors have been shown to have an influence on cognitive scores. Conclusions: Age at menarche correlated with cognitive outcomes. Our study suggests that earlier exposure to endogenous estrogens during a phase of development and plasticity of the brain might preserve women with PD from cognitive decline. Full article

Background: Endocrine therapy (ET) with or without ovarian function suppression (OFS) is a cornerstone treatment for estrogen receptor-positive (ER+) breast cancer (BC) in premenopausal women, but its impact on quality of life (QoL) and sexual health remains a concern. Methods: We conducted a multicenter, prospective, observational study including premenopausal women (≤50 years) diagnosed with stage I–III ER+ BC and treated in private healthcare facilities in Brazil between 2013 and 2023. Patients received ET alone (ET-only) or combined with OFS (OFS-ET). QoL was assessed at baseline and 3, 6, 9, 12, and 24 months using the EORTC QLQ-BR23. Sexual functioning and sexual enjoyment were prespecified primary outcomes. Logistic regression identified factors associated with OFS use, and Fisher’s exact test was applied for categorical comparisons at 24 months. Results: Among 363 patients (80% ET-only, 20% ET + OFS), younger age, advanced stage, and chemotherapy were independently associated with OFS use. Both groups reported early declines in sexual functioning and enjoyment. By 24 months, ET-only patients had returned to baseline, whereas OFS patients remained below baseline. At the item level, no significant differences were observed in sexual desire (51.5% vs. 42.0%; p = 0.33) or enjoyment (26.0% vs. 13.5%; p = 0.20). Lack of sexual activity was more frequent in the OFS group (60.6% vs. 41.2%; p = 0.05). Body image was significantly more impaired with OFS, with a higher proportion of patients reporting feeling less attractive (38.2% vs. 19.9%; p = 0.04) and less feminine (26.5% vs. 11.7%; p = 0.05). Conclusions: ET impairs sexual health in young BC survivors, particularly when combined with OFS. These findings underscore the need for routine sexual health assessments and supportive interventions in survivorship care. Full article

Background and Objectives: Post-menopausal estrogen decline is considered a contributing factor to sarcopenia, and inspiratory muscle training (IMT) may provide benefits in this demographic. This study examined the impact of a four-week IMT program on diaphragm thickness, abdominal wall muscle thickness (AWMT; transversus abdominis, internal oblique, and external oblique), and liver fat percentage in healthy elderly women. Materials and Methods: Twenty-six women aged 60–80 years were randomly assigned to an IMT group (n = 13) or a control group (n = 13). The IMT group used the PowerBreathe^® Classic device at 40% of maximal inspiratory pressure (MIP), with weekly increments of 10%. Training was performed twice daily, five days per week, with 30 breathing cycles per session (60 per day). The control group maintained their usual routines. AWMT, diaphragm thickness (DT), and fatty liver density (FLD) were measured by a radiologist before and after the intervention. Results: After four weeks, the IMT group showed significant improvements in all parameters compared to controls. Mid-diaphragm thickness (MDT) increased by 11.44% (effect size (ES) = 0.358, p < 0.001) versus 0.76% in controls (p = 0.271). Posterior diaphragm thickness (PDT) improved by 7.48% (ES = 0.282, p < 0.001) versus 0.38% (p = 0.564). Right AWMT increased by 12.7% (ES = 0.492, p < 0.001) compared to 0.10% (p = 0.872), and left AWMT increased by 9.93% (ES = 0.395, p < 0.001) versus 2.64% (p = 0.014). FLD improved by 11.79% (ES = 0.959, p < 0.001) in the IMT group, while the control group showed no meaningful change (−0.13%, p = 0.847). Conclusions: A short-term IMT protocol significantly enhanced diaphragm and AWMT and reduced liver fat in elderly women. These findings support the use of IMT as a simple, non-invasive intervention to preserve musculoskeletal and metabolic health in aging populations. Full article