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Search Results (1,932)

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12 pages, 2607 KB  
Article
The Role of 3D/4D Transperineal Ultrasound in Risk Stratification for Pelvic Organ Prolapse Recurrence: Native Tissue Versus Mesh Repair
by José Antonio García-Mejido, María José Nuñez-Matas, Olaya Salas-Álvarez, Alejandro Crespo-Rodriguez, Ana Fernández-Palacín and José Antonio Sainz-Bueno
J. Clin. Med. 2026, 15(12), 4627; https://doi.org/10.3390/jcm15124627 (registering DOI) - 14 Jun 2026
Abstract
Background/Objectives: Pelvic organ prolapse (POP) management requires precise patient selection for surgical techniques to balance clinical efficacy and safety. The primary aim of this study was to evaluate the role of preoperative 3D/4D transperineal ultrasound in the risk stratification of POP recurrence. [...] Read more.
Background/Objectives: Pelvic organ prolapse (POP) management requires precise patient selection for surgical techniques to balance clinical efficacy and safety. The primary aim of this study was to evaluate the role of preoperative 3D/4D transperineal ultrasound in the risk stratification of POP recurrence. We analyzed the impact of levator ani muscle (LAM) injuries, specifically avulsion and ballooning, as identified by ultrasound, on both anatomical and subjective success rates, comparing native tissue repair versus mesh-augmented surgery. Methods: A prospective, multicenter observational study was conducted over a five-year period, January 2021 to December 2024 (recruitment), with follow-up completed in December 2025, ensuring a minimum follow-up of 12 months for all participants. The cohort included 276 women scheduled for primary surgery for symptomatic POP stage ≥ 2. Prior to intervention (116 underwent native tissue repair and 160 received mesh), all patients underwent 3D/4D transperineal ultrasound for standardized volume acquisition. Using this preoperative functional imaging technique, we measured the hiatal area and diagnosed the presence of hiatal ballooning (≥25.0 cm2) or levator muscle avulsion. Results: Ultrasound assessment revealed significant differences in surgical success based on the diagnosed baseline site-specific defects. Hiatal ballooning was the sonographic finding that demonstrated the greatest impact on risk stratification. Among patients with preoperative ballooning, mesh use significantly reduced both subjective recurrence (5.7% vs. 21.4%, p = 0.001) and objective recurrence (21.4% vs. 35.7%, p = 0.040) compared to native tissue repair. Furthermore, in women without ultrasound-documented avulsion, mesh also decreased objective recurrence (17.9% vs. 33.0%, p = 0.024). Multivariate analysis, adjusted for age, BMI, menopausal status, and parity, confirmed that, after stratifying by these preoperative ultrasound findings, a native tissue approach remains the primary independent predictor of surgical failure (OR 1.752 for objective recurrence; p = 0.041). Conclusions: In conclusion, native tissue repair was identified as the primary independent predictor of surgical failure. While 3D/4D transperineal ultrasound helps identify high-risk phenotypes such as hiatal ballooning, these sonographic findings did not maintain independent significance in the multivariate model. Therefore, ultrasound should be considered a complementary tool for surgical planning rather than a definitive predictor of recurrence. Full article
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21 pages, 3402 KB  
Review
Insomnia in Breast Cancer: A Neglected Symptom Cluster
by Giuseppe Marano, Ida Paris, Gianandrea Traversi, Osvaldo Mazza, Antonella Migliore, Valentina Ricozzi, Silvia Rotondaro, Francesco Pavese, Tatiana D’Angelo, Paola Fuso, Alessandra Fabi, Gianluca Franceschini and Marianna Mazza
J. Clin. Med. 2026, 15(12), 4603; https://doi.org/10.3390/jcm15124603 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Insomnia is one of the most prevalent and persistent symptoms among patients with breast cancer, yet it remains under-recognized and undertreated in routine clinical practice. Beyond its impact on sleep quality, insomnia is increasingly understood as a multidimensional condition involving neurobiological, [...] Read more.
Background/Objectives: Insomnia is one of the most prevalent and persistent symptoms among patients with breast cancer, yet it remains under-recognized and undertreated in routine clinical practice. Beyond its impact on sleep quality, insomnia is increasingly understood as a multidimensional condition involving neurobiological, psychological, and behavioral mechanisms, closely intertwined with cancer-related stress and psychiatric comorbidities. This narrative review aims to provide a comprehensive and integrative overview of insomnia in breast cancer, focusing on its epidemiology, pathophysiological underpinnings, neuropsychiatric correlates, and clinical implications, while highlighting gaps in current research and management. Methods: A narrative review of the literature was conducted, including studies published in major medical databases (PubMed, Scopus, and Web of Science) up to 2025. Relevant articles addressing insomnia, sleep disturbances, psychiatric symptoms, and neurobiological mechanisms in breast cancer populations were selected and synthesized. Results: Insomnia affects a substantial proportion of breast cancer patients across the disease trajectory, from diagnosis to survivorship. Its etiology is multifactorial, involving dysregulation of the hypothalamic–pituitary–adrenal axis, inflammatory processes, and circadian rhythm, as well as treatment-related factors such as chemotherapy, endocrine therapy, and menopausal symptoms. Insomnia frequently co-occurs with depression, anxiety, fatigue, and pain, forming symptom clusters that significantly impair quality of life and may influence clinical outcomes. Emerging evidence supports a bidirectional relationship between insomnia and psychiatric vulnerability, suggesting a shared neurobiological substrate within the brain–body stress axis. Conclusions: Insomnia in breast cancer should be conceptualized as a neuropsychiatric condition embedded within a broader stress-related symptom network rather than as an isolated sleep disturbance. Improved screening, interdisciplinary management, and the integration of evidence-based interventions such as cognitive behavioral therapy for insomnia are essential. Research should focus on personalized and mechanistically informed approaches to better address this highly prevalent yet insufficiently managed condition. Full article
(This article belongs to the Special Issue Breast Cancer: Advances in Clinical and Personalized Practices)
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23 pages, 3204 KB  
Article
Cervicovaginal Microbiota and Biogenic Amine Metabolic Shifts in HPV-Associated Cervical Disease
by Natalie M. Meléndez-Vázquez, Nataliya Chorna, Cecilia Noecker, Andrea P. Cortes-Nazario, Josefina Romaguera and Filipa Godoy-Vitorino
Cancers 2026, 18(12), 1931; https://doi.org/10.3390/cancers18121931 (registering DOI) - 13 Jun 2026
Abstract
Background: Cervical cancer is primarily caused by the human papillomavirus (HPV), with persistent infections progressing to low- (LGSIL) and high-grade (HGSIL) lesions. Emerging evidence indicates that the cervicovaginal microbiota influences HPV persistence and disease progression, although the underlying metabolic mechanisms remain unclear. [...] Read more.
Background: Cervical cancer is primarily caused by the human papillomavirus (HPV), with persistent infections progressing to low- (LGSIL) and high-grade (HGSIL) lesions. Emerging evidence indicates that the cervicovaginal microbiota influences HPV persistence and disease progression, although the underlying metabolic mechanisms remain unclear. Therefore, we assessed the relationship between the cervicovaginal microbiota and the metabolic milieu in women with cervical dysplasia and HPV infections. Methods: We recruited 36 non-menopausal, non-pregnant women who were classified as negative, LGSIL, or HGSIL based on pathology and HPV results. Cervical swabs were collected for genomic DNA extraction to characterize bacterial communities using 16S rRNA sequencing and to perform HPV genotyping. Cervical lavages were collected for untargeted metabolomic profiling using Gas Chromatography-Mass Spectrometry. Integrative multiomic analysis was performed using the MIMOSA2 pipeline. Results: Although bacterial community structure was not different between groups, women with HGSIL had higher richness and exhibited a higher abundance of Prevotella bivia, Prevotella buccalis, and Lachnospiraceae G-9 oral taxon 924. Lesion-positive samples had shifts in tyramine and putrescine, biogenic amines linked to cancer development. Specifically, Pseudomonas was identified as a potential contributor to tyramine oxidation. Conclusions: Cervical lesions and HPV risk are associated with shifts in the cervicovaginal microbial metabolic milieu, highlighting the role of low-abundant anaerobic bacteria. Despite the small sample size, biogenic amines were associated with anaerobic taxa and microbial dysbiosis. These findings warrant further assessment of microbial-derived metabolites and their potential to promote tumor progression by driving a pro-inflammatory, metabolically altered microenvironment. Full article
28 pages, 1482 KB  
Review
Exploring the Health Effects of Phytoestrogens
by Vladimír Kraus, Anna Birková, Miroslava Majerníková and Beáta Čižmárová
Metabolites 2026, 16(6), 410; https://doi.org/10.3390/metabo16060410 (registering DOI) - 12 Jun 2026
Viewed by 72
Abstract
Background/Objectives: Phytoestrogens are secondary plant metabolites produced via the phenylpropanoid pathway. They include a broad spectrum of chemical compounds, such as phenolics, flavonoids, isoflavones, coumestans, lignans, and others. Their chemical structures resemble those of estradiol, and they exhibit biological effects similar to those [...] Read more.
Background/Objectives: Phytoestrogens are secondary plant metabolites produced via the phenylpropanoid pathway. They include a broad spectrum of chemical compounds, such as phenolics, flavonoids, isoflavones, coumestans, lignans, and others. Their chemical structures resemble those of estradiol, and they exhibit biological effects similar to those of human estrogens, influencing many physiological processes throughout life in both men and women—including the timing and progression of puberty. Methods: The literature search included databases such as PubMed, Scopus, Web of Science, and Google Scholar with the use of specific keywords. Studies were considered eligible if they reported original findings from observational studies (cohort, case–control, and cross-sectional) or from experimental studies. Results: Phytoestrogens can modulate estrogenic activity and interact with a variety of biological pathways. These compounds may play a role in human development and pubertal processes, contribute to overall health, and potentially help alleviate menopausal symptoms and reduce the risk of certain cancers. Conclusions: Phytoestrogens have numerous positive effects on the human body across various stages of life. Their overall impact and potency, however, seem to be influenced by factors such as intake level, individual genetic variability, and the specific phytoestrogen class consumed. Full article
(This article belongs to the Special Issue Effects of Secondary Plant Metabolites on Human Health)
14 pages, 2786 KB  
Article
Biomechanical and Parenchymal Determinants of Pain Perception During Mammography: Three-Dimensional Biometric Measurements and the Need for Personalized Compression
by Abdulkadir Eren, Emrah Karatay and Irmak Durur Subasi
Diagnostics 2026, 16(12), 1819; https://doi.org/10.3390/diagnostics16121819 (registering DOI) - 12 Jun 2026
Viewed by 130
Abstract
Background/Objectives: Standard mechanical compression applied during screening mammography is a primary barrier that reduces patient compliance. Current guidelines attempt to standardize compression based solely on the one-dimensional “breast thickness” measured by the device. This study aimed to investigate the effects of three-axis [...] Read more.
Background/Objectives: Standard mechanical compression applied during screening mammography is a primary barrier that reduces patient compliance. Current guidelines attempt to standardize compression based solely on the one-dimensional “breast thickness” measured by the device. This study aimed to investigate the effects of three-axis anatomical breast dimensions, applied compression force, menstrual cycle phases, and BI-RADS breast density patterns on pain scores during mammography within a comprehensive biomechanical model. Methods: This retrospective cohort study included 443 female patients who underwent routine screening or diagnostic mammography. Patients with a history of breast implants, lactation, or prior breast surgery that could alter tissue biomechanics were excluded. Maximum pain scores (1–10 on a Visual Analog Scale [VAS]) were recorded. Transverse, anteroposterior, and superoinferior breast biometric measurements for each patient were calculated using advanced radiological workstations. Data were analyzed using One-Way ANOVA and Multiple Linear Regression (OLS) models. Results: The mean age of the participants was 49.7 ± 9.4 years, the mean applied compression force was 62.4 ± 10.3 N, and the mean pain score was 2.03 ± 2.12 (range: 1–10). The multiple linear regression analysis was statistically significant overall (F = 2.516, p = 0.015). Having a BI-RADS Type D (extremely dense) breast pattern was identified as the strongest independent factor associated with an increased pain score (p = 0.082, coefficient = 1.219). Age showed a trend toward a negative effect on pain (p = 0.072), while compression force showed a trend toward a positive effect (p = 0.067). Conversely, breast thickness (p = 0.231) and the three-dimensional mean breast size index (p = 0.568) demonstrated no independent predictive power. The menstrual cycle phase did not reach independent significance in the multivariate regression model (p = 0.117); however, non-parametric univariate analysis revealed a significant difference in pain across hormonal groups (Kruskal–Wallis H = 10.04, p = 0.039), with actively menstruating and luteal-phase women reporting higher pain than menopausal women. Conclusions: The pain experienced during mammography depends on the internal fibroglandular architecture (elasticity and stiffness) of the tissue rather than its external volumetric dimensions. Notably, neither device-measured breast thickness nor manually calculated three-dimensional breast dimensions independently predicted pain, challenging the widespread assumption that breast size drives mammographic discomfort. “One-size-fits-all” or thickness-based compression strategies should be abandoned in routine practice. Instead, “personalized compression” protocols that prioritize patient comfort without compromising image quality should be developed, particularly for younger patients and those with BI-RADS Type D, and to a lesser extent Type C, density patterns. Full article
(This article belongs to the Special Issue Recent Advances in Gynecological and Pediatric Imaging)
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18 pages, 1565 KB  
Article
Lipid and Apolipoprotein Profiles in Pre- and Postmenopausal Breast Cancer Patients with and Without Neoadjuvant Chemotherapy Exposure: A Cross-Sectional Analysis
by María Pilar Carrera-González, María Jesús Ramírez-Expósito, Cristina Cueto-Ureña and José Manuel Martínez-Martos
Appl. Sci. 2026, 16(12), 5910; https://doi.org/10.3390/app16125910 - 11 Jun 2026
Viewed by 64
Abstract
Breast cancer (BC) is associated with metabolic factors that may influence circulating lipids and apolipoproteins. We performed a cross-sectional observational study including 198 women with infiltrating ductal breast carcinoma and 78 cancer-free controls. In the analyzed data, the breast cancer cohort included 39 [...] Read more.
Breast cancer (BC) is associated with metabolic factors that may influence circulating lipids and apolipoproteins. We performed a cross-sectional observational study including 198 women with infiltrating ductal breast carcinoma and 78 cancer-free controls. In the analyzed data, the breast cancer cohort included 39 premenopausal and 44 postmenopausal women without neoadjuvant chemotherapy (NACT), and 35 premenopausal and 54 postmenopausal women exposed to NACT; controls included 63 premenopausal and 52 postmenopausal women. Serum ApoA1 and ApoB were measured by ELISA, and HDL and LDL cholesterol were measured by enzymatic methods. Analyses included two-way ANOVA, Tukey post hoc testing, false-discovery-rate correction, and multivariable linear models adjusted for age and BMI, with HC3 robust sensitivity analyses. In cancer patients, HDL was lower in women exposed to NACT (adjusted β= −8.16, 95% CI −12.61 to −3.71), and ApoA1 differed by menopausal status. Subtype-aware analyses in the available subset did not show independent molecular subtype effects after multiplicity correction. These findings support cross-sectional associations between menopausal status, treatment exposure, and lipid/apolipoprotein profiles, but do not establish causality or prognostic value. Prospective longitudinal studies are required. Full article
16 pages, 8553 KB  
Article
Dental Tissue-Derived Mesenchymal Stem Cells Modulate Mitochondrial and OPG/RANKL Signaling in Obesity-Associated Osteoporosis Under Estrogen-Deficient and Intact Conditions
by Saet-Byul Kim, Chae-Yeon Hong, Won-Jae Lee, Hyeon-Jeong Lee, Chan-Hee Jo, Seo-Yoon Kang, Sanghyeon Park, Yeung Bae Jin, Tae-Sung Hwang, Jaemin Kim, Yong-ho Choe and Sung-Lim Lee
Biomedicines 2026, 14(6), 1320; https://doi.org/10.3390/biomedicines14061320 - 10 Jun 2026
Viewed by 218
Abstract
Background/Objectives: Obesity and menopause are major determinants of skeletal deterioration; however, their combined effects on bone remodeling and associated cellular bioenergetics remain incompletely understood. This study aimed to determine whether obesity induces osteoporotic alterations under both estrogen-replete and estrogen-deficient conditions and to [...] Read more.
Background/Objectives: Obesity and menopause are major determinants of skeletal deterioration; however, their combined effects on bone remodeling and associated cellular bioenergetics remain incompletely understood. This study aimed to determine whether obesity induces osteoporotic alterations under both estrogen-replete and estrogen-deficient conditions and to evaluate the therapeutic potential of dental tissue-derived mesenchymal stem cells (D-MSCs). Methods: Female mice were subjected to ovariectomy (OVX) and/or high-fat diet (HFD) feeding for 16 weeks to establish obesity-associated osteoporosis models. D-MSCs were administered intraperitoneally at defined intervals. Body weight and serum leptin levels were measured to assess metabolic status. Femoral tissues were analyzed by quantitative real-time PCR for estrogen receptors (ERα, ERβ), inflammatory markers (Il-1β, Tnf-α), mitochondrial regulators (Pgc1α, Pgc1β), and the OPG/RANKL ratio. Histological analysis was performed to evaluate bone marrow adiposity. Results: HFD significantly increased body weight and serum leptin levels in both intact and OVX mice. Obesity was associated with reduced expression of ERα and ERβ, decreased Pgc1α levels, and a lower OPG/RANKL ratio, accompanied by increased Il-1β, Tnf-α, and Pgc1β expression. D-MSC administration attenuated body weight gain and reduced leptin levels, particularly in OVX mice. In femoral tissue, D-MSC treatment restored estrogen receptor expression, increased Pgc1α, decreased Pgc1β, and normalized the OPG/RANKL ratio. In addition, inflammatory marker expression and bone marrow adiposity were reduced following MSC administration. Conclusions: Obesity induces bone remodeling dysregulation under both intact and estrogen-deficient conditions, characterized by altered estrogen signaling, inflammatory activation, and mitochondrial imbalance. D-MSC administration was associated with partial restoration of these alterations, suggesting a potential role in modulating metabolic and skeletal homeostasis in obesity-associated bone loss. Full article
(This article belongs to the Section Gene and Cell Therapy)
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20 pages, 1501 KB  
Review
Menopausal Hormone Therapy and Cardiovascular Risk: Current Evidence and Clinical Implications
by Catalin M. Buzduga, Amelian M. Bobu, Roxana Covali, Claudia Florida Costea, Andrei I. Cucu, Mariana Graur, Emilia Patrascanu, Iustina Solomon-Condriuc and Alexandru Carauleanu
Med. Sci. 2026, 14(2), 298; https://doi.org/10.3390/medsci14020298 - 10 Jun 2026
Viewed by 226
Abstract
Background: Menopausal hormone therapy (MHT) effectively relieves vasomotor symptoms, but its cardiovascular safety remains influenced by timing, formulation, and route of administration. Methods: This narrative review summarizes evidence from major randomized trials (WHI, HERS, ELITE, DOPS) and observational studies, along with mechanistic data [...] Read more.
Background: Menopausal hormone therapy (MHT) effectively relieves vasomotor symptoms, but its cardiovascular safety remains influenced by timing, formulation, and route of administration. Methods: This narrative review summarizes evidence from major randomized trials (WHI, HERS, ELITE, DOPS) and observational studies, along with mechanistic data on the vascular and metabolic effects of MHT. Results: Although early studies suggested cardioprotection, randomized trials showed no cardiovascular benefit, and in some cases, increased risks of coronary events, stroke, and venous thromboembolism, particularly in older women or those with established cardiovascular disease. The “timing hypothesis” indicates that early initiation after menopause may have neutral or modestly favorable effects, whereas late initiation is associated with adversity. Oral estrogen is linked to higher thromboembolic and stroke risk compared with transdermal formulations. Evidence on atrial fibrillation and heart failure remains limited. Conclusions: MHT should not be used for cardiovascular disease prevention. Current evidence suggests that younger women in the early postmenopausal period may derive the greatest benefit with the lowest risk from individualized hormone therapy regimens, particularly those using transdermal estrogen. Treatment decisions should be guided by careful cardiovascular risk assessment and targeted to symptom relief and osteoporosis prevention. Full article
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11 pages, 937 KB  
Article
Circulating GPER-1, 8-Iso-Prostaglandin F2α, and Raftlin-1 in Hypertensive Women During the Menopausal Transition: Associations with BMI and Diagnostic Performance
by Ünal Öztürk, Muhammed Mehdi Üremiş and Ergül Belge Kurutaş
J. Clin. Med. 2026, 15(12), 4484; https://doi.org/10.3390/jcm15124484 - 10 Jun 2026
Viewed by 93
Abstract
Background: Hypertension (HTN) is a multifactorial condition involving alterations in vascular signaling, inflammation, and oxidative stress. Women during the menopausal transition may experience increased cardiovascular risk due to hormonal fluctuations, highlighting the need for circulating biomarkers that may assist in identifying HTN-related biological [...] Read more.
Background: Hypertension (HTN) is a multifactorial condition involving alterations in vascular signaling, inflammation, and oxidative stress. Women during the menopausal transition may experience increased cardiovascular risk due to hormonal fluctuations, highlighting the need for circulating biomarkers that may assist in identifying HTN-related biological changes. This study aimed to evaluate circulating biomarkers reflecting estrogen signaling, inflammation, and oxidative stress, and to assess their diagnostic accuracy in HTN. Methods: This cross-sectional study included 54 treatment-naïve hypertensive women and 30 age-matched normotensive controls, all in the menopausal transition period. Serum levels of GPER-1, 8-iso-PGF2α, raftlin-1, and estradiol were measured using ELISA. Associations between biomarkers and body mass index (BMI) were examined using Spearman correlation. Diagnostic discrimination was examined using ROC curve analysis, and optimal cut-off points were determined using the Youden index. Results: Serum levels of GPER-1, 8-iso-PGF2α, and raftlin-1 were significantly higher in the HTN group compared to controls, while estradiol showed a modest increase. No significant associations were found between BMI and any of the measured biomarkers within the HTN group. ROC analysis demonstrated that 8-iso-PGF2α and raftlin-1 showed the highest diagnostic accuracy for distinguishing HTN patients from controls, followed by GPER-1, whereas estradiol showed limited diagnostic value. High sensitivity and specificity values further supported the diagnostic potential of 8-iso-PGF2α and raftlin-1. Conclusions: These findings suggest that serum raftlin-1 and 8-iso-PGF2α levels may serve as potential biomarkers for distinguishing hypertension in women during the menopausal transition, while GPER-1 also demonstrated good diagnostic accuracy. The lack of association with BMI suggests relative independence from adiposity-related effects. However, further validation in larger and well-characterized cohorts is required. Full article
(This article belongs to the Section Cardiovascular Medicine)
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12 pages, 635 KB  
Review
Association Between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Vasomotor Symptoms: A Scoping Review
by Anastasia Ntikoudi, Anastasia Papachristou, Afroditi Tsalkitzi, Despoina Rizikou, Eleni Evangelou, George Mastorakos and Eugenia Vlachou
Endocrines 2026, 7(2), 27; https://doi.org/10.3390/endocrines7020027 - 9 Jun 2026
Viewed by 147
Abstract
Background: Vasomotor symptoms (VMS), particularly hot flashes and night sweats, are highly prevalent during the menopausal transition and have been increasingly associated with adverse cardiometabolic profiles. Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major manifestation of systemic metabolic dysregulation and is rising [...] Read more.
Background: Vasomotor symptoms (VMS), particularly hot flashes and night sweats, are highly prevalent during the menopausal transition and have been increasingly associated with adverse cardiometabolic profiles. Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major manifestation of systemic metabolic dysregulation and is rising globally. Emerging evidence suggests a potential overlap between menopausal symptom severity and MASLD risk; however, this relationship remains insufficiently characterized. Method: A scoping review was conducted in accordance with PRISMA-ScR guidelines to map the existing evidence on the association between VMS and MASLD. A comprehensive search of PubMed, Scopus, CINAHL, Cochrane Library, and MEDLINE was performed for English-language studies published between January 2015 and December 2025. Eligible studies included original research assessing both MASLD and menopausal symptoms. Data were extracted and synthesized narratively. Methodological quality was appraised using the CASP Cross-Sectional Studies Checklist. Results: Of 690 identified records, five cross-sectional studies met the inclusion criteria, comprising 106 to 5995 participants from Korea, Greece, and the United States. Across studies, moderate-to-severe VMS were consistently associated with increased MASLD prevalence or higher surrogate indices of hepatic steatosis. Women with more severe VMS demonstrated unfavorable metabolic profiles, including greater insulin resistance and elevated liver enzyme levels. Although adjustments for body mass index and hypertension attenuated some associations, the overall trend remained positive. Heterogeneity was observed in diagnostic tools and symptom assessment methods. Conclusions: Current evidence indicates a consistent association between VMS severity and MASLD in peri- and postmenopausal women. While causality cannot be inferred due to cross-sectional designs, VMS may represent a clinical marker of underlying metabolic and hepatic dysfunction. Longitudinal and mechanistic studies are warranted to clarify directionality and inform integrated screening strategies in midlife women. Full article
(This article belongs to the Section Endocrine Immunology, Cytokines and Cell Signaling)
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22 pages, 1343 KB  
Systematic Review
Endogenous Sex Hormones (FSH, Oestradiol, Testosterone and SHBG) and Type 2 Diabetes Risk in Postmenopausal Women: A Systematic Review and Meta-Analysis
by Carolyn Chia-Yu Liu, Carola S. König and Sudarshan Ramachandran
Endocrines 2026, 7(2), 26; https://doi.org/10.3390/endocrines7020026 - 8 Jun 2026
Viewed by 197
Abstract
Background/Objectives: Menopause is accompanied by substantial changes in endogenous sex hormones that influence metabolic regulation. However, the associations of specific hormones with type 2 diabetes (T2D) risk in postmenopausal women remain inconsistent. This study aimed to quantify the relationships between incident T2D and [...] Read more.
Background/Objectives: Menopause is accompanied by substantial changes in endogenous sex hormones that influence metabolic regulation. However, the associations of specific hormones with type 2 diabetes (T2D) risk in postmenopausal women remain inconsistent. This study aimed to quantify the relationships between incident T2D and follicle-stimulating hormone (FSH), oestradiol, testosterone, and sex hormone-binding globulin (SHBG), and to examine cross-sectional differences in hormone concentrations between postmenopausal women with and without T2D. Methods: MEDLINE, Embase and Cochrane CENTRAL were searched from database inception to 21 June 2024. Eligible studies included prospective cohort, nested case–control and case–control designs. Associations with incident T2D were pooled using Hartung–Knapp–Sidik–Jonkman random-effects meta-analysis. Both categorical and continuous estimates were extracted, prioritising maximally adjusted models. Risk of bias was assessed using ROBINS-E and the Newcastle–Ottawa Scale. Results: Sixteen studies (18 articles; n = 16,180) were included. Higher SHBG was consistently associated with lower T2D risk in cohort analyses (RR 0.55; 95% CI 0.38–0.72; I2 ≈ 0%). Higher FSH was also associated with lower risk (high vs. low: HR 0.55, 95% CI 0.29–0.81), although continuous estimates showed heterogeneity. Higher oestradiol was associated with increased T2D risk (RR 1.61, 95% CI 1.18–2.03; I2 ≈ 6%), while testosterone was not significantly associated with incident T2D (RR 1.11, 95% CI 0.73–1.50). Cross-sectional analyses indicated lower SHBG and higher testosterone in women with T2D. Conclusions: Endogenous hormone profiles and SHBG concentrations are associated with T2D in postmenopausal women, with the most consistent evidence for an inverse association between SHBG and incident T2D. Because the available evidence is observational and partly heterogeneous, these findings should be interpreted as associations rather than causal or clinically predictive effects. Standardised measurement, repeated pre-diagnostic sampling and external validation are required before these biomarkers can be considered for routine risk stratification. Full article
(This article belongs to the Special Issue Feature Papers in Endocrines 2026)
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18 pages, 1447 KB  
Review
Chronic Opioid Use and Endocrine Disruption in Women: Mechanisms, Life-Course Vulnerabilities, and Reproductive Health Implications
by Doonyah Alucozai and Elizabeth Kwo
J. Xenobiot. 2026, 16(3), 106; https://doi.org/10.3390/jox16030106 - 7 Jun 2026
Viewed by 262
Abstract
Chronic opioid use disrupts the female endocrine system, affecting the hypothalamic–pituitary–gonadal (HPG), hypothalamic–pituitary–adrenal (HPA), and hypothalamic–pituitary–thyroid (HPT) axes. In women, these disruptions manifest as menstrual irregularity, infertility, early menopause, reduced bone mineral density, adrenal insufficiency, and altered mood and sexual function. Despite the [...] Read more.
Chronic opioid use disrupts the female endocrine system, affecting the hypothalamic–pituitary–gonadal (HPG), hypothalamic–pituitary–adrenal (HPA), and hypothalamic–pituitary–thyroid (HPT) axes. In women, these disruptions manifest as menstrual irregularity, infertility, early menopause, reduced bone mineral density, adrenal insufficiency, and altered mood and sexual function. Despite the magnitude of the opioid epidemic and its impact on women of reproductive age, the existing evidence base is overwhelmingly male: across the major studies of opioid-induced endocrinopathy reviewed here, 99.5 percent of participants were male. Sex-specific mechanisms, prevalence estimates, and clinical thresholds therefore remain poorly defined, and current guidelines do not adequately address the reproductive, skeletal, and adrenal consequences of chronic opioid exposure in women. This review synthesizes available human and preclinical evidence on opioid-induced endocrine dysfunction in women across the lifespan, distinguishing established findings from hypotheses extrapolated from male or animal data. We propose a practical framework for routine endocrine screening of HPG, HPA, and HPT axis function, bone health, and fertility, and outline the roles of relevant specialties in multidisciplinary care. Available evidence suggests a substantial risk of endocrine dysfunction in women on chronic opioid therapy, but the precise prevalence remains unknown. Sex-sensitive research, guidelines, and routine screening are urgently needed to close this gap. Full article
(This article belongs to the Special Issue Environmental Exposures and Their Impact on Reproduction)
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14 pages, 1020 KB  
Article
Vitamin D Status and Reproductive Hormonal Profiles in Early Versus Physiological Menopause: A Comparative Observational Study
by Anamaria Ardelean, Cristian Furău, Oana Toduț, Nicoleta Mirica, Florina Buleu, Simona Ioana Sipos, Ion Petre, Izabella Petre, Tiberiu Buleu, Mircea Iurciuc, Oana Suciu and Roxana Furău
Biomedicines 2026, 14(6), 1283; https://doi.org/10.3390/biomedicines14061283 - 4 Jun 2026
Viewed by 321
Abstract
Background: An early menopause (by definition, menopause that occurs at a woman’s age 40 through 45) is often associated with certain changes in the body that can result in risks for health-related conditions, an extended period later. Thus, scientists have begun examining how [...] Read more.
Background: An early menopause (by definition, menopause that occurs at a woman’s age 40 through 45) is often associated with certain changes in the body that can result in risks for health-related conditions, an extended period later. Thus, scientists have begun examining how vitamin D has been suggested to be associated with endocrine function regulating both hormones and reproductive function during this time. However, it is not yet clear as to whether or not vitamin D provides any benefit to women who have experienced an early menopause. Material and Methods: The data was collected from 272 women in this retrospective, observational study at The County Hospital, Department of Obstetrics and Gynecology, Arad. The method of grouping the sample included two stratifications into early and physiological menopause categories based on amenorrhoea for a minimum of 12 consecutive months. 25-hydroxyvitamin D (25(OH)D) levels were classified into three categories: deficiency (<20 ng/mL), insufficiency (21–29 ng/mL), or adequacy (≥30 ng/mL). Estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) hormone parameters were measured using standard immunoassays. The analysis employed correlation and regression to evaluate potential relationships between 25(OH)D levels and hormone parameters. Results: A significant proportion of the study group had a vitamin D deficiency. This was supported by the fact that only 24.27% of women were identified as having adequate levels of vitamin D, while the rest (62.03%) did not. Women in the early menopause group had a statistically significant negative relationship between estradiol and FSH (i.e., r = −0.29, p = 0.0016), as well as between progesterone and LH (i.e., r = −0.207, p = 0.026). There was not a statistically significant relationship between total sample vitamin D and estradiol (i.e., r = −0.038, p = 0.686) nor between vitamin D and progesterone (i.e., r = 0.031, p = 0.744). Women with vitamin D blood levels of 30 ng/mL or more showed a strong negative relationship between vitamin D and estradiol (r = −0.780; p = 0.0016) and a moderate positive relationship with progesterone (r = 0.534; p = 0.0104). However, these relationships were inconsistent in other groups. All group comparative analyses showed that women in the early menopause group had much lower estradiol levels than those in the physiological menopause group, regardless of whether they were classified based on their vitamin D levels (p < 0.0001). Conclusions: Women experiencing early or physiological menopause are at risk of having low vitamin D levels. However, our study results do not show a consistent relationship between serum 25(OH)D concentrations and serum estradiol or progesterone concentrations among the study population, suggesting that vitamin D is not a major factor influencing hormonal changes during menopause. These findings were inconsistent across analyses and should be interpreted cautiously. Overall, the results do not support a significant association between serum 25(OH)D concentrations and reproductive hormone levels in our study population. Full article
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19 pages, 1399 KB  
Review
Sex Differences in Oxidative Stress: Role of Dietary and Nutraceutical Antioxidants and Clinical Implications
by Alessandra Ventre, Enrica Dato, Marilena Di Salvo, Marco Casciaro and Sebastiano Gangemi
Appl. Sci. 2026, 16(11), 5544; https://doi.org/10.3390/app16115544 - 2 Jun 2026
Viewed by 345
Abstract
Oxidative stress occurs when reactive oxygen species exceed the capacity of antioxidant defenses, causing molecular damage and alterations in cellular signaling. This process is characterized by interindividual variability, particularly based on biological sex. Hormones such as estrogens, which exert antioxidant effects, and androgens, [...] Read more.
Oxidative stress occurs when reactive oxygen species exceed the capacity of antioxidant defenses, causing molecular damage and alterations in cellular signaling. This process is characterized by interindividual variability, particularly based on biological sex. Hormones such as estrogens, which exert antioxidant effects, and androgens, which can act as pro-oxidants in certain contexts, along with genetic and epigenetic factors linked to sex chromosomes, contribute to the sex-specific regulation of redox homeostasis. Nutraceuticals, including polyphenols, vitamins, carotenoids, and omega-3 fatty acids, influence oxidative processes through both direct and indirect mechanisms. This review evaluates the impact of biological sex on oxidative stress mechanisms and responses to nutraceutical antioxidants, synthesizing the results of molecular, metabolic, and clinical studies published over the past decade. The current literature indicates that biological sex influences both basal redox balance and individual responses to antioxidant mechanisms. Generally, males have a higher oxidative load and may benefit more from supplementation, while females typically possess greater antioxidant capacity, primarily due to hormonal influences. Greater consideration of sex as a biological variable is essential to optimize nutraceutical strategies and develop personalized interventions for oxidative stress-related diseases. Full article
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15 pages, 314 KB  
Article
Psychological Burden and Psychosocial Stress in Younger and Middle-Aged Women with Prior Myocardial Infarction
by Mira Stipčević, Ivana Jurin, Marijana Knežević Praveček, Kristina Selthofer-Relatić, Laura Dražić, Marta Lugarić, Ognjen Čančarević, Šime Manola, Irzal Hadžibegović, Kristina Marić Bešić, Luka Matej Mahečić, Vedran Radonić, Ana Pavlović, Tomislav Krčmar and Matias Trbušić
Medicina 2026, 62(6), 1082; https://doi.org/10.3390/medicina62061082 - 2 Jun 2026
Viewed by 227
Abstract
Background and Objectives: Younger and middle-aged women may continue to describe psychological and psychosocial burden years after myocardial infarction (MI), yet multicenter real-world data remain limited on what women retrospectively report during long-term follow-up. This study examined such reports in younger and [...] Read more.
Background and Objectives: Younger and middle-aged women may continue to describe psychological and psychosocial burden years after myocardial infarction (MI), yet multicenter real-world data remain limited on what women retrospectively report during long-term follow-up. This study examined such reports in younger and middle-aged women with prior MI while explicitly accounting for delayed, heterogeneous follow-up timing and the non-standardized nature of symptom ascertainment. Materials and Methods: We performed a cross-sectional analysis within a Croatian multicenter cohort of 957 women younger than 60 years hospitalized with STEMI or NSTEMI between 1 February 2020 and 28 February 2025. Psychological information was collected retrospectively during routine follow-up; the formal PHQ-4 instrument was not administered. A study-specific four-item summary informed by PHQ-4 content was described, and exploratory multivariable analyses modelled this summary as a continuous variable. Descriptive timing-stratified sensitivity analyses and a timing-restricted continuous-score sensitivity model were additionally performed. Results: Prior psychiatric diagnosis was recorded in 16.0% of women, post-MI psychiatric diagnosis in 31.4%, and any psychosocial stressor in 73.2%. Among women with complete item responses, the four-item summary showed a broad distribution rather than a discrete threshold pattern. In continuous-score analyses, higher observed summary values were associated with younger age, prior psychiatric diagnosis, any psychosocial stressor, non-partnered status, non-employment, pregnancy complications/adverse pregnancy outcomes, and greater peri-menopausal symptom burden. Median summary values were only modestly higher in the small ≤ 1-year stratum and were otherwise similar across the later follow-up strata. Higher summary values were also associated with lower odds of self-reported regular current statin-based lipid-lowering use. Conclusions: These findings are best interpreted as exploratory data on retrospectively reported and currently endorsed long-term psychological and psychosocial burden years after MI, not as contemporaneous measures of recovery-phase psychopathology. Prospective studies with predefined assessment windows and validated instruments are needed. Full article
(This article belongs to the Special Issue Acute Coronary Syndromes: Diagnosis, Management, and Risk Prediction)
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