Search Results (819)

Background/Objectives: Menopause is a complex physiological transition characterized by progressive estrogen deficiency and systemic biological changes that can affect multiple organs and tissues, including the oral cavity. Growing evidence suggests that hormonal fluctuations during the menopausal transition may influence periodontal health, salivary function, oral sensory perception, and overall oral health-related quality of life. Objective: This narrative review aims to provide a comprehensive overview of the biological mechanisms and clinical manifestations associated with the relationship between menopause and oral health, with particular attention to periodontal outcomes, salivary changes, oral discomfort, dental status, and the potential role of hormone replacement therapy (HRT). Methods: This narrative review was based on a structured literature search conducted in PubMed/MEDLINE and Scopus to identify studies published between January 2005 and May 2026. Predefined eligibility criteria were applied to identify relevant human studies. The retrieved evidence was synthesized narratively according to major oral health domains and menopausal phenotypes. Results: Fifty studies met the inclusion criteria. Overall, menopause was associated with poorer periodontal parameters, including increased probing depth, clinical attachment loss, and periodontal inflammation. Reduced salivary flow, dry mouth, altered salivary composition, burning symptoms, and taste disturbances were frequently reported in peri- and postmenopausal women. A higher prevalence of caries and tooth loss was also reported, although the contribution of age and other confounding factors varied across studies. New evidence suggests that estrogen deficiency may influence oral health through interconnected pathways involving immune regulation, bone metabolism, salivary gland function, and host–microbiome interactions. Evidence regarding the effects of HRT has been mixed, although several studies have reported improvements in salivary function and periodontal outcomes among treated women. Conclusions: Menopause appears to act as an important systemic modifier of oral health through multifactorial biological mechanisms. Menopause-associated oral manifestations go beyond local tissue changes and reflect broader interactions between hormonal status, inflammation, bone metabolism, and microbial ecology. Increased awareness among dental and medical professionals and a multidisciplinary approach could improve the prevention, diagnosis, and management of oral diseases in postmenopausal women. Further, well-designed longitudinal studies are needed to clarify causal relationships and identify effective therapeutic strategies. Full article

Sex- and gender-based immune differences have often been interpreted through a male–female biological binary, overlooking how endocrine signaling dynamically shapes immune function. Gender-affirming hormone therapy (GAHT) offers a unique physiological model to disentangle the effects of sex steroids from chromosomal background and examine immune plasticity in contexts relevant to reproductive health. This hormone-informed framework proposes that estradiol and testosterone regulate immune set-points across innate, adaptive, metabolic, and mucosal compartments. Through genomic and non-genomic signaling via androgen and estrogen receptors (AR, ERα/β), these hormones drive distinct immune outcomes: testosterone dampens type I interferon responses in plasmacytoid dendritic cells and reshapes monocyte inflammatory profiles, while estradiol promotes macrophage polarization and enhances T helper1 (Th1) responses. Hormonal effects are closely coupled to cellular metabolism: androgen signaling acts as a “metabolic brake” on Th17 cells by limiting glutaminolysis, a process reinforced by epigenetic remodeling, and is reflected in shifts in the circulating metabolome, positioning metabolomics as a sensitive tool for monitoring hormone-driven immune adaptation. Regardless, hormones also reshape mucosal barriers and reproductive microbiome composition. GAHT alters vaginal and gut microbial communities and their metabolism, influencing mucosal immunity, local inflammation, and reproductive tract homeostasis, with potential implications for fertility preservation, susceptibility to reproductive tract infections, and long-term genital mucosal health. Collectively, this evidence underscores that human immunity is highly responsive to endocrine context. This review synthesizes evidence linking endocrine trajectories, tissue microenvironments, reproductive biology, and social determinants of health, aiming to advance understanding of immune plasticity and contribute to a more inclusive framework of human immune diversity. Full article

Background/Objectives: Endocrine-disrupting chemicals (EDCs) interfere with hormonal homeostasis and have been implicated in gynecological malignancy pathogenesis. This narrative review synthesizes current evidence regarding EDC exposure and breast, endometrial, ovarian, and cervical cancers, examining molecular mechanisms, epidemiology, and diagnostic and clinical implications. Methods: We conducted a literature review using PubMed/MEDLINE, Embase, Scopus, and Cochrane databases through April 2026, including systematic reviews, meta-analyses, prospective cohorts, case-control studies, and mechanistic investigations examining EDC-cancer associations. Methodological quality was appraised using the Newcastle-Ottawa Scale and AMSTAR-2, with overall certainty of evidence rated using the GRADE framework. Results: Major EDC classes—bisphenol compounds, phthalates, polychlorinated biphenyls, organochlorine pesticides, and per- and polyfluoroalkyl substances—demonstrate carcinogenic potential through estrogen receptor modulation, epigenetic alterations, oxidative stress, and oncogenic signaling disruption. Breast cancer shows the strongest evidence, with prenatal and early-life DDT/DDE exposure associated with up to a 3.7-fold increased risk. Endometrial cancer demonstrates associations with xenoestrogen mixtures exhibiting non-monotonic dose-responses, whereas ovarian and cervical cancers show emerging but limited associations. Common mechanisms include receptor crosstalk, epigenetic dysregulation with transgenerational effects, oxidative genomic instability, metabolic reprogramming, and cancer stem cell enrichment. Conclusions: Evidence supports EDC contributions to gynecological malignancy through convergent pathways, though causal inference remains constrained by observational epidemiology, long latency periods, and challenges in characterizing real-world mixture exposures. Diagnostic and prevention strategies should integrate EDC exposure into risk-prediction models, leverage multi-omics biomarkers for early detection, and emphasize exposure reduction during critical developmental windows alongside regulatory reform. Full article

This narrative review examines perimenopause as a critical transitional phase in women’s lives, often accompanied by elevated vulnerability to anxiety and depression. Dysfunction of the gut–brain axis is one of the key factors contributing to perimenopausal mood disorders and is currently receiving extensive attention. GBA dysfunction can trigger neurotransmitter metabolic imbalance, intestinal barrier impairment, and neuroinflammatory responses. Tryptophan (Trp) and γ-aminobutyric acid (GABA) serve as essential precursors and direct modulators of key neurotransmitters, and the dysregulation of their metabolic pathways has been implicated in perimenopausal anxiety and depression in animal models and limited clinical observations. Trp influences 5-hydroxytryptamine (5-HT) by affecting emotional states. GABA is the primary inhibitory neurotransmitter in the central nervous system and is closely associated with anxiety and depression. Fluctuations in estrogen levels during perimenopause significantly alter the composition and metabolic activity of the gut microbiota, which in turn affects Trp metabolism and GABA synthesis through increased intestinal permeability, activation of immune-inflammatory responses, and disruption of hypothalamic–pituitary–adrenal (HPA) axis function. Although traditional hormone replacement therapy and pharmacological treatments are effective, they are associated with some side effects. Preliminary evidence from in vitro and animal studies suggests that nutritional interventions targeting Trp and GABA metabolism within the gut–brain axis may offer a novel research direction, though their efficacy in perimenopausal women remains to be established. Potential nutritional strategies, including supplementation with Trp and its precursors, inhibition of the kynurenine pathway (KP), and supplementation with probiotics and prebiotics, can modulate Trp and GABA metabolism. This review focuses on Trp and GABA metabolic regulation via the gut–brain axis to explore pathogenesis of perimenopausal anxiety and depression and summarize potential nutritional intervention targets, thereby providing a scientific basis for emotional management in perimenopausal women. Full article

Background: Endometriosis is a chronic, estrogen-dependent inflammatory disorder associated with pain and immune dysregulation. Omega-3 (n-3) fatty acids and fish-derived bioactive lipids may modulate inflammation and metabolism. This study investigated whether adding fish-derived lipids (FDLs) to a Healthy Eating Plate diet improves inflammatory markers, gut inflammation, pain, and quality of life in women with endometriosis. Methods: In this 12-week randomized controlled trial, 46 women with confirmed endometriosis were assigned to either a Healthy Eating Plate diet alone (control group, CG) or the same diet plus FDLs (intervention group, IG). Primary outcomes included serum cytokine concentrations (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha [TNF-α]) and fecal calprotectin (CAL). Secondary outcomes included pain intensity measured using the visual analog scale (VAS) and health-related quality of life assessed with the Endometriosis Health Profile-30 (EHP-30). Results: IL-10 levels (pg/mL) increased in the IG (32.5 ± 51.5 to 265 ± 508; p = 0.024) with a significant adjusted effect (ANCOVA: 5.07 [95% CI: 1.32–19.48], p = 0.019). Other cytokines showed heterogeneous responses, and CAL levels remained unchanged. EHP-30 Pain scores improved within both groups (CG p = 0.016; IG p = 0.002) without significant between-group change or adjusted effects (all p > 0.05). VAS scores decreased within the IG (5.0 ± 2.1 to 4.3 ± 2.1; p = 0.011), although there were no between-group differences in change and ANCOVA (all p > 0.05). However, ≥1-point responder rates were higher in the IG vs. CG (73.9% vs. 34.8%): adjusted RR = 2.11 (95% CI: 1.16; 3.89; p = 0.014). Conclusions: Overall, FDL supplementation was associated with a selected regulatory immune signal, reflected mainly by the IL-10 response, while most inflammatory, pain-related, and quality-of-life outcomes did not show consistent significant between-group effects. The observed greater likelihood of pain reduction in the FDL-supplemented group of women with endometriosis, along with the IL-10 response, should be interpreted with caution and confirmed in larger studies with longer follow-up/intervention time, taking into account the potential mechanisms of biological response. Full article

Background: Endometriosis and lipedema are chronic female-predominant disorders characterized by persistent pain that is frequently disproportionate to anatomical lesion burden. Although traditionally interpreted within distinct lesion-centered frameworks, both conditions exhibit striking clinical and epidemiological parallels, including hormonally modulated symptom dynamics, overlap with central pain syndromes, weak correlation between structural disease severity and pain intensity, and symptom clustering during reproductive transitions such as puberty, pregnancy, and menopause. Methods: This study aims to synthesize clinical, molecular, neuroimmune, and endocrine evidence on the interrelationship between endometriosis and lipedema, and to propose a hypothesis-generating neuroimmune framework linking both conditions. This integrative narrative review conducted a non-systematic literature search in PubMed/MEDLINE, Scopus, and Web of Science, focusing on mechanisms related to chronic pain, mast cell biology, TRPV1 signaling, CGRP-mediated neurogenic inflammation, intracrine steroidogenesis, and peripheral and central sensitization. Results: The review identifies convergent biological characteristics between the two diseases, including mast cell activation, macrophage polarization, endothelial dysfunction, fibrosis, angiogenesis, intracrine estrogen metabolism, and persistent inflammatory signaling. In endometriosis, direct evidence demonstrates increased sensory innervation, nerve growth factor expression, TRPV1 sensitization, CGRP-positive fibers, and mast cell-nerve interactions. In lipedema, convergent upstream mechanisms, including mast cell infiltration, elevated histamine levels, adipose tissue inflammation, and local estrogen activation, support the plausibility of a functionally analogous neuroimmune organization, despite incomplete direct neural characterization. In this context, the mast cell-TRPV1-CGRP axis is proposed as a biologically plausible framework, directly supported in endometriosis and currently hypothetical in lipedema, connecting peripheral sensitization, neurogenic inflammation, hormonal chronodependence, and central nociceptive amplification. The model further conceptualizes pain crises as transient events of instability within a sensitized neuroimmune network and proposes mechanistic phenotypes that integrate gastrointestinal, inflammatory, central, and hormonal triggers. Conclusion: Endometriosis and lipedema may represent topographically distinct manifestations of a shared neuroimmune process operating within hormone-sensitive tissues. Although the evidentiary basis remains asymmetric, with stronger mechanistic support in endometriosis than in lipedema, this framework provides a biologically plausible and experimentally testable model integrating endocrine, immune, neural, and vascular contributors to chronic pain amplification. This perspective supports coordinated translational investigation across reproductive biology, endocrinology, and pain medicine and may contribute to future mechanism-based stratification and therapeutic development. This work is hypothesis-generating and is not intended to establish causality or to provide clinical recommendations; all proposed mechanistic and therapeutic inferences require prospective experimental validation. Full article

Background/Objectives: Estrogen deficiency is associated with metabolic disturbances and impaired glucose homeostasis. Morin, a natural flavonol, has shown promising hypoglycemic and antioxidant properties, but its effects under hypoestrogenic diabetic conditions remain poorly understood. The aim of this study was to evaluate the effects of morin on body weight, fasting blood glucose, glucose tolerance, and selected serum biochemical markers in an experimental model of diabetes under estrogen-deficient conditions (ovariectomized diabetic female mice). Methods: Female CD1 mice underwent sham surgery or ovariectomy (OVX), and each surgical condition was further divided into non-diabetic and diabetic subgroups treated with vehicle, glibenclamide (10 mg/kg), or morin (30 mg/kg). Body weight and fasting blood glucose were monitored over a 15-day treatment period. Oral glucose tolerance was assessed on day 15, and serum biochemical markers, including glucose, cholesterol, triglycerides, uric acid, blood urea nitrogen, creatinine, ALT, and AST, were measured thereafter. Results: Ovariectomy aggravated diabetes-associated hyperglycemia, impaired glucose tolerance, and triglyceride elevation. Morin treatment reduced fasting blood glucose and improved glucose tolerance in diabetic mice, including ovariectomized animals. Morin also attenuated the increase in serum triglycerides and blood urea nitrogen in ovariectomized diabetic mice, although it did not significantly improve cholesterol, uric acid, creatinine, ALT, or AST levels. Compared with glibenclamide, morin showed relevant glucose-lowering activity but had a more limited effect on the overall biochemical profile. Conclusions: These findings suggest that morin may partially improve glycemic control and selected metabolic alterations in experimental diabetes associated with estrogen deficiency. Further studies are required to clarify its mechanisms of action, long-term efficacy, and translational relevance. Full article

Total RNA was isolated from sections of healthy testes and Leydig cell tumors of mixed-breed dogs using TMA Master II device. The RNA-seq libraries were sequenced on the Illumina platform. Following differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were applied with quality control obtained using FastQC and Trimmomatic. This analysis revealed 1500 transcripts, including 982 upregulated and 168 downregulated genes. The results demonstrated that a significant proportion of these differentially expressed genes are directly involved in the control of sex steroid production (CYP11A1, STAR, and 3β-HSD3B1) or tube formation, angiogenesis, and extracellular matrix remodeling in interstitial cells (ESM1, FGG, and VEGFA). Moreover, we identified the upregulation of transcripts responsible for neurotransmitter or neuroendocrine signaling (SLC6A4, GRIN2C, GABRB3) and cholesterol metabolism and its regulation (GPX3, MSMO1, DHCR24). These genes were strongly associated with the phosphatidylinositol-3-kinase (PI3K)-Protein Kinase B (Akt) cascade and extracellular matrix interactions, features shared with various malignancies. Alterations in estrogen and relaxin signaling appear to be distinctive, understudied mechanisms specific to canine Leydig cell tumors. Concurrently, downregulated genes (e.g., DMRTC2, SEMA3C, ALOX12) were linked with cell differentiation, signaling and immunoregulatory pathway suppression involved in tumorigenesis. A complex transcriptomic profile of canine Leydig cell tumors was developed, revealing a conserved oncogenic core shared in some aspects with human malignancies alongside unique species-specific alterations. Findings seem to be useful for identifying novel diagnostic biomarkers and targeted therapies in veterinary oncology, establishing canine reproductive tissues as a valuable comparative biomedical model for research in human. Full article

Junken meat sheep exhibit a characteristic postnatal coat-color transition, in which the initially black fleece gradually fades and develops into a white-trunk phenotype; however, the transcriptional basis of this developmental change in follicular pigment output remains unclear. In this study, three Junken meat sheep lambs showing a natural postnatal black-to-white coat-color transition were sampled longitudinally at the newborn black-fleece stage and the 179-day white-trunk stage, generating three matched biological pairs for RNA-seq analysis. Representative candidate genes were further validated by RT-qPCR. Differential expression analysis identified 1657, 400, and 1086 differentially expressed genes in the C11 vs. C1, C22 vs. C2, and C33 vs. C3 comparisons, respectively. Functional enrichment analysis indicated that these genes were mainly associated with tyrosine metabolism, ECM–receptor interaction, focal adhesion, Phosphoinositide 3-kinase-Akt signaling pathway (PI3K-Akt), arachidonic acid metabolism, estrogen signaling, and immune-related pathways. Integrated analysis of shared downregulated genes and expression patterns highlighted candidate genes related to pigmentation, the ECM/follicular microenvironment, and regulatory or metabolic processes. Pigmentation-related genes, including SOX10, TYR, TYRP1, PMEL, OCA2 and SLC45A2, were generally downregulated in 179-day white-trunk-stage skin, while changes in ECM- and metabolism-related genes suggested altered follicular microenvironmental regulation. These findings identify candidate transcriptional features associated with developmental coat-color fading in Junken meat sheep and support a follicular microenvironment–melanogenesis expression axis as a transcriptome-based framework for further investigation. Full article

Backgrounds/Objectives: Allele frequencies of genetic variants associated with complex diseases can contribute to varying degrees to predisposition depending on the population’s genetic profile. The aim of this study was to analyze the genetic diversity of 15 relevant SNVs that could modulate bone and cartilage metabolism in underrepresented structured populations. Methods: In a sample of 130 Mestizos and 304 natives from 8 native Mexican populations, SNVs related to multifactorial diseases were genotyped using a SNaPShot Multiplex kit and analyzed via capillary electrophoresis using an ABI PrismTM 3130 Genetic Analyzer (Applied Biosystems, Waltham, MA, USA.), and genetic profiles for 15 SNVs were obtained using GeneMapper software v. 3.2. Allele frequencies were calculated by locus and population using Power Stats and Arlequin v.3.1 software, for which the EM algorithm was used to compare reference populations obtained from the dbSNV database of the International HapMap project. Population structure, paired comparisons, and genetic differentiation between native, admixed, and reference populations (p value) were estimated through Fst tests using the STRUCTURE v.2.3.2 and Arlequin v.3.1 software. Results: Haplotype frequency combinations grouped as profiles showed higher predominance in the allelic combination A/A/G for rs9340799 (ESR1), rs700518 (CYP19A1), and rs1800795 (IL6) genes, respectively. Conclusions: Allelic profiles could be useful as medical tools for preventing and managing individuals or populations. Mexican populations showed high genetic variability among allelic risk profiles for estrogen control and response, as well as high frequencies of variant combinations associated with an increased inflammatory response, potentially resulting in high osteoclastogenesis. This analysis advances our understanding of the complexity of bone and cartilage metabolism in highly stratified populations. Full article

Purpose: Obesity is a chronic multifactorial disease whose increasing prevalence cannot be fully explained by excessive caloric intake and sedentary behaviour alone. This review aimed to synthesize current evidence on the role of endocrine-disrupting chemicals (EDCs), particularly obesogenic EDCs, as potential environmental contributors to obesity-related phenotypes, with emphasis on their main classes, etiopathogenetic mechanisms and clinical implications. Methods: A structured literature analysis was conducted using PubMed, Web of Science and additional relevant scientific reports and governmental publications. Eligible sources included original research articles, systematic reviews, meta-analyses and authoritative reports addressing endocrine disruption, obesogens, obesity, metabolic dysfunction and related molecular mechanisms. Results: The review identified several major classes of obesogenic EDCs, including organotins, bisphenols, phthalates and persistent organic pollutants. These compounds have been linked to obesity-related phenotypes through overlapping mechanisms, including disruption of adipogenesis via estrogen receptor-dependent and independent pathways, PPARγ/RXR activation, altered adipokine signalling, neuroendocrine dysregulation across developmental stages, oxidative stress and pro-inflammatory activation, genetic and epigenetic alterations, gut microbiota-mediated effects and impaired thermoregulation through brown and beige adipose tissue dysfunction. EDC-associated obesity may contribute to metabolic, endocrine, cardiovascular, hepatic and reproductive complications. Conclusion: Obesogenic EDCs should be regarded as environmental contributors to obesity that act through interconnected molecular, cellular and systemic pathways. Their biological effects support the need for further mechanistic and epidemiological research, preventive strategies, public education and regulatory measures aimed at reducing exposure. Full article

Background: Caffeine is one of the most widely consumed bioactive compounds worldwide. The available data regarding its effects on bone metabolism and skeletal health remain inconsistent. The aim of this study was to review experimental studies on the effects of caffeine on the skeletal system. Methods: A literature search was conducted using PubMed to identify original experimental studies investigating the effects of caffeine on the skeletal system published up to December 2025. The reviewed studies included in vivo studies on different animal models and in vitro studies on bone-related cells. Due to data heterogeneity, a narrative analysis was performed. Results: Fifty-three studies on caffeine effects were included in the review. The findings indicate that the effects of caffeine are dose-dependent and bidirectional. Low-to-moderate doses in vivo generally exerted neutral or sometimes beneficial effects on the skeletal system, whereas higher doses were associated with impaired bone development, reduced mineralization, and increased bone loss. In estrogen-deficient animals, moderate doses showed potential protective effects, while high doses exacerbated bone loss. In vitro studies demonstrated concentration-dependent effects, with high concentrations often reducing cell viability and osteogenic activity. Conclusions: The effects of caffeine on the skeletal system are complex and context-dependent. While high exposure may adversely affect bone, low-to-moderate intake appears to be safe and may exert beneficial effects under specific conditions. Full article

Endometriosis is increasingly recognized as a chronic systemic disorder extending beyond the classical estrogen-dependent paradigm, integrating metabolic, immune, fibrotic, and nociceptive pathways that sustain lesion persistence and refractory pelvic pain. We propose a mechanistic, translational hypothesis in which tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, may modulate four interconnected pathological axes of refractory endometriosis—Warburg-type metabolic reprogramming with lactate accumulation, peritoneal immune dysfunction, NF-κB/NLRP3/TGF-β1-driven inflammatory–fibrotic remodeling, and persistent nociceptive sensitization—through three convergent molecular nodes: AMPK-associated signaling, GLP-1 receptor activity in peritoneal macrophages and spinal microglia, and the NF-κB/NLRP3/TGF-β1 axis. Particular emphasis is placed on the concept of “peritoneal incretin deficiency”, characterized by reduced peritoneal GLP-1 concentrations and increased expression of incretin-degrading proteases. This concept currently rests on a single, non-replicated case–control study, and the broader mechanistic chain is supported largely by indirect evidence extrapolated from adjacent inflammatory, metabolic, and neuroimmune disease models rather than by endometriosis-specific data. Direct experimental or clinical validation in endometriosis-specific models is currently absent. Accordingly, this article represents a hypothesis-generating framework rather than evidence of established efficacy, or a clinical treatment recommendation, intended to guide future mechanistic and prospective clinical investigation of incretin-based modulation as a potential adjunctive strategy in refractory endometriosis. Full article

The gut microbiota and its metabolites, as components of the gut–bone axis, play a pivotal role in regulating skeletal homeostasis through the bidirectional communication network. In this systematic review, evidence was collected from mainstream databases following standardized inclusion/exclusion criteria for screening, to comprehensively retrieve and screen eligible studies from multiple mainstream databases according to standardized inclusion and exclusion criteria, and systematically summarize current research progress on plant-derived bioactive compounds targeting the gut–bone axis for skeletal health regulation. This review systematically explores the underlying mechanisms of the gut–bone axis and critically evaluates the regulatory effects and therapeutic potential of plant-derived bioactive compounds. Particular attention is given to targeted interventions involving prebiotics, probiotics, synbiotics, and plant-rich diets or functional foods. Among these interventions, synbiotics represent the most successful strategy and show the most prominent therapeutic possibilities in bone-related disorders. Different from single prebiotics (only nourish endogenous intestinal microbes), individual probiotics (easy to be degraded in gastrointestinal tract with poor colonization) and ordinary plant-rich diets (unfixed effective dosage and weak targeting property), synbiotics combine prebiotic carriers and viable probiotic strains to produce complementary advantages, which is the core reason for its outstanding therapeutic prospect against bone diseases. Synbiotics exert synergistic effects on gut microecology, mineral absorption, and immune regulation, leading to more robust and consistent improvements in bone health than single prebiotics, probiotics, or general plant-rich diets. They have been verified in preclinical and clinical studies to ameliorate osteoporosis and related skeletal diseases via the gut–bone axis. These strategies offer novel insights into the prevention and treatment of bone metabolic disorders, such as osteoporosis, by targeting the gut–bone axis with phytochemicals. Key outcomes of this review include that synbiotics, soy isoflavones, naringin, curcumin, and resveratrol effectively improve bone mineral density, restore gut microbiota balance, and inhibit pathological bone resorption via the gut–bone axis. Collectively, the above bioactive substances realize bone protection mainly by reshaping gut flora, elevating mineral uptake and suppressing excessive osteoclast activity. Representative cases include soy isoflavones mitigating estrogen-deficient bone loss in OVX models, naringin improving the trabecular microarchitecture, and probiotic BL-11 promoting longitudinal bone growth in children. Future directions will focus on clarifying dose–response relationships, developing standardized synbiotic formulations, constructing microbiome-guided precision diets, and conducting large-sample randomized controlled trials to translate plant-derived compounds into clinical therapies. Full article

Background/Objectives: Gender-affirming hormone therapy (GAHT) is associated with clinically relevant changes in body composition, energy metabolism, and functional capacity in transgender and gender-diverse individuals. The nutritional implications of these adaptations remain insufficiently characterized, and current assessment models, largely derived from cisgender populations, may not fully capture hormone-related body composition and metabolic changes. This narrative review aims to synthesize the metabolic and body composition effects of GAHT, evaluate methodological limitations in assessing nutritional status, and propose an integrated framework for clinical nutritional management. Methods: A narrative literature review was conducted through searches of PubMed/MEDLINE, Scopus, and Web of Science, complemented by screening of relevant guidelines and reference lists. Priority was given to longitudinal studies, mechanistic studies, systematic reviews, meta-analyses, and clinical guidance addressing GAHT-related changes in body composition, metabolism, nutritional status, and functional outcomes. Results: Available evidence suggests that GAHT is associated with sex steroid-related, tissue-specific changes in body composition and metabolism. In transgender men, testosterone is generally associated with increases in lean body mass (LBM), reductions in fat mass, and potential increases in visceral adiposity, alongside possible increases in energy expenditure and altered cardiometabolic profiles. In transgender women, estrogen therapy, combined with androgen suppression, is generally associated with reductions in LBM and redistribution of subcutaneous fat, with heterogeneous metabolic and functional responses. Across both groups, changes in body composition are not consistently reflected by the Body Mass Index or functional outcomes, suggesting a possible dissociation between structural and functional adaptation. Common assessment tools show limitations, including reliance on cisgender-derived reference standards and inability to capture dynamic hormonal transitions. Conclusions: Current evidence supports the need for a longitudinal and individualized interpretation of nutritional and body composition changes during GAHT. A shift toward longitudinal, multimodal nutritional assessment, integrating body composition, functional measures, biochemical markers, dietary intake, and clinical context, may improve clinical monitoring and reduce misclassification. Full article