Obesity is a major contributor to chronic disease and multimorbidity, leading to progressively increasing clinical complexity across the life course. However, the relationship between obesity and overall clinical complexity remains insufficiently characterized, particularly at the population level, where territorial and socioeconomic inequalities should also be considered. In this review, we summarize the current evidence and complement it with an in-depth characterization of the demographic, socioeconomic, clinical, and healthcare utilization burden associated with obesity in a population of 8 million people in Catalonia, Spain. Beyond individual comorbidities, we examine multimorbidity using a comprehensive risk stratification measure and evaluate the impact of obesity on healthcare resource utilization and expenditure. Obesity was more prevalent among women and socioeconomically disadvantaged populations and followed a marked geographic deprivation gradient. Compared with a reference population standardized by age, sex, and socioeconomic status, individuals with obesity had a substantially greater multimorbidity burden, with 13
Pituitary neuroendocrine tumors (PitNETs) are common intracranial neoplasms with heterogeneous hormonal activity, invasiveness, and treatment response. Conventional MRI is central to diagnosis, but is limited in quantifying tumor heterogeneity and predicting clinically relevant features such as consistency, molecular subtype, proliferation, and clinical outcomes. To review current evidence on MRI-based radiomics and artificial intelligence (AI) in PitNETs, focusing on clinical applications, methodological quality, and future integration into precision medicine. Narrative review of studies published between 2019 and 2025 evaluating radiomics, machine learning, and deep learning applied to PitNETs, highlighting tumor consistency, molecular and histological subtypes, proliferation, invasiveness, treatment response, recurrence, visual outcomes, and differential diagnosis of sellar lesions. Radiomics has been applied across the PitNET clinical trajectory. Texture- and shape-based features from T2-weighted and multiparametric MRI predict intraoperative tumor consistency with AUCs often > 0.80, outperforming conventional radiology. Radiomic signatures allow non-invasive differentiation of functional vs. non-functional adenomas, somatotroph granulation patterns, silent corticotroph adenomas, prolactinomas, and prediction of Ki-67 and PIT-1 expression. Models also predict cavernous sinus invasion, postoperative regrowth, recurrence, visual outcomes, and treatment response, including dopamine-agonist therapy. Differential diagnosis of hypophysitis and Rathke’s cleft cyst has also been explored. Methodological quality remains heterogeneous, with frequent single-center, retrospective designs, limited external validation, and suboptimal adherence to reporting guidelines. Radiomics and AI show promise for risk stratification and personalized therapy in PitNETs, particularly for predicting tumor consistency, molecular subtypes, and recurrence. Clinical implementation requires standardized imaging protocols, multicenter datasets, reproducible segmentation, interpretable models, and prospective validation.
Diabetes encompasses a heterogeneous group of metabolic disorders characterized by hyperglycemia resulting from inadequate insulin secretion and/or impaired insulin action. A central, common feature across all major forms of diabetes is the loss of functional pancreatic β-cell mass. Recent advancements have significantly highlighted the critical role of pancreatic β-cell in diabetes, primarily driven by advances in genome-wide and multi-omics approaches, the availability of isolated human islets, and the data from large clinical trials. This review synthesizes current evidence on the pathogenesis of different diabetes types including monogenic diabetes (MD), type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes (GD), from the perspective of the pancreatic β-cell, emphasizing its contribution to disease heterogeneity and progression. In MD, single-gene defects directly impair β-cell function, highlighting the genetic basis of insulin secretion and offering insights into personalized treatment. In T1D, β-cells are not merely passive targets of autoimmunity but may actively participate in initiating immune responses through stress-induced changes. T2D is characterized by β-cell failure in the context of insulin resistance (IR), with genetic and functional studies underscoring the key role of β-cell decline in disease development. GD results from an inadequate β-cell compensatory response to pregnancy-related IR, revealing the intrinsic metabolic defect. Overall, a β-cell-centered framework helps elucidate the diverse mechanisms underlying different types of diabetes, provides a mechanistic foundation for improved disease subclassification.
Under normal physiological conditions, hypothalamic resident immune cells interact with neurons and other non-neuronal cells to maintain tissue homeostasis. Accumulated evidence from studies with rodents shows that excessive intake of saturated fatty acids triggers hypothalamic neuroinflammation, innate and adaptive immune activation, and chemotaxis of peripheral immune cells toward the hypothalamus. The functional consequences of this immune activation are not uniformly detrimental, as specific immune subsets can instead support metabolic resilience. Beyond this functional heterogeneity, the structural mechanisms underlying immune cell recruitment within the arcuate nucleus (ARC) and median eminence (ME), particularly extracellular matrix (ECM) and neurovascular remodeling, remain poorly defined. To address this gap, this review integrates established mechanisms from other central nervous system compartments with recent hypothalamic findings, proposing a framework for how structural changes, including microgliosis, tanycyte barrier breakdown, and ECM and neurovascular remodeling, orchestrate immune-metabolic adaptations within the ARC and ME under nutritional stress. We further provide an overview of the hypothalamic immune landscape and describe how microglia, perivascular macrophages, and tanycytes, are involved with this hypothalamic niche remodeling.
Fibroblast growth factor 23 (FGF23) was identified as an etiological factor for hypophosphatemic rickets/osteomalacia approximately a quarter-century ago. Since then, FGF23 has been shown to be a bone-derived hormone that regulates phosphate and vitamin D metabolism by binding to the α-KLOTHO-FGF receptor complex. Dysregulation of FGF23 activity results in hypophosphatemic and hyperphosphatemic disorders. Medical therapy targeting FGF23 is now available for hypophosphatemic diseases caused by FGF23 excess. Furthermore, elevated FGF23 levels have been associated with various adverse clinical outcomes, including left ventricular hypertrophy, cardiovascular events, vascular calcification, and increased mortality. Beyond its role in mineral metabolism, FGF23 has been reported to exert direct effects on other organs, contributing to conditions such as left ventricular hypertrophy, anemia, and cardiac and renal fibrosis. However, the exact mechanisms underlying these pleiotropic actions have not yet been fully elucidated. This review summarizes recent findings regarding FGF23, focusing on its classical role as a hormone and its broader effects as a humoral factor on other organs.
Thyroid cancer represents the most prevalent malignancy of the endocrine system, with its incidence exhibiting a significant rise in recent years. Diagnostic methods have undergone profound evolution over the past century, progressing from basic clinical examination to a sophisticated and technology-centered approach. Initially, the diagnosis of thyroid neoplasms relied on physical examination and palpation, with definitive diagnoses being stated after postoperative histopathological analysis. The mid-twentieth century brought the emergence of imaging techniques, including radionuclide scanning and, later, high-resolution ultrasound, which revolutionized non-invasive detection, enabling earlier and more precise identification of thyroid lesions. The subsequent introduction of fine-needle aspiration (FNA) cytology fundamentally transformed diagnostic algorithms, optimizing preoperative risk stratification and reducing the number of unnecessary surgical interventions. This review outlines the historical development of thyroid cancer diagnostics and highlights major clinical practice milestones.
Weight regain is the defining challenge of obesity treatment and remains insufficiently addressed in current clinical paradigms. Despite substantial initial weight loss achieved through lifestyle, pharmacological, or surgical interventions, most individuals experience partial or complete regain over time, reflecting powerful and persistent biological adaptations that defend body weight. These include reductions in energy expenditure, sustained hormonal changes that promote appetite, and neurobehavioral mechanisms that favor increased energy intake, all of which are further modulated by genetic and epigenetic susceptibility. In this context, we integrate current mechanistic evidence with real-world data from the IGOBE program, a structured multidisciplinary lifestyle intervention, to provide novel insights into the dynamics of weight regain. While participants achieved comparable initial weight loss, long-term trajectories diverged markedly, revealing two distinct phenotypes: maintainers and regainers. Strikingly, baseline clinical and behavioral characteristics failed to predict outcomes. Individuals who ultimately regained weight displayed more favorable baseline lifestyle profiles, whereas sustained weight loss was associated with greater longitudinal behavioral change, particularly in physical activity, dietary patterns, and self-regulation. These findings challenge the prevailing assumption that weight regain is primarily a consequence of poor adherence and instead support a model in which long-term outcomes emerge from the interaction between biological pressures and the capacity for sustained behavioral adaptation. We argue that obesity management must be fundamentally reframed: long-term weight maintenance should replace initial weight loss as the primary therapeutic goal, and treatment should adopt a chronic care model integrating continuous support, personalized strategies, and, when appropriate, sustained pharmacotherapy.
The mammary gland is a composite organ in which epithelial ducts and alveoli develop within a specialized adipose-rich stroma. Although mammary biology has traditionally been interpreted through an epithelium-centered framework, increasing evidence indicates that mammary adipocytes actively shape mammary development, reproductive remodeling, and disease susceptibility. Across puberty, pregnancy, lactation, and involution, mammary adipocytes undergo dynamic changes in cellular state, morphology, lipid handling, and stromal interactions, reflecting fate-related, phenotypic, and metabolic plasticity. Through adipokines, growth factors, metabolic substrates, extracellular matrix (ECM)-associated mechanical cues, and immune–inflammatory networks, mammary adipocytes influence epithelial behavior and tissue remodeling. Conversely, epithelial expansion, secretory differentiation, and post-weaning regression reshape the adipose-rich stromal niche. Dysregulation of this reciprocal adipose–epithelial ecosystem may contribute to aberrant tissue expansion, local estrogenic or inflammatory amplification, impaired adipose support, and tumor-permissive remodeling. Here, we review stage-specific epithelial–adipocyte crosstalk during mammary development, define mammary adipocyte plasticity across fate-related and functional dimensions, and discuss its relevance to benign breast disorders, tumor-associated remodeling, and disease susceptibility.
Thyroid peroxidase (TPO) is a crucial enzyme in thyroid hormone (TH) biosynthesis, catalyzing iodination and coupling reactions for triiodothyronine (T3) and thyroxine (T4) production. In addition to the known enzymatic inhibition mediated by some compounds, increasing evidence indicates that various drugs can modulate TPO mRNA and/or protein expression (e.g., protein kinase activators, cytokines, epigenetic drugs). This review comprehensively explores current evidence on the pharmacological regulation of TPO expression, encompassing its molecular structure, enzymatic function, and involvement in physiological and pathological conditions (e.g., thyroid cancer, autoimmune thyroid diseases, congenital hypothyroidism and hyperthyroidism). Among compounds reported to affect TPO expression, the antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) show variable effects across in vitro and in vivo models, yielding heterogeneous and sometimes conflicting results. Considering that ATDs are the only class of drugs known to directly target TPO and the current lack of works gathering all the related information, there is a need for clarifying ATD-mediated modulation of TPO expression. A systematic PubMed search identified 437 records, of which 22 original studies met inclusion criteria in this work. Overall, available data suggest time-, dose-, and species-dependent ATD effects on TPO expression, highlighting the need for further research to determine clinical relevance.
To investigate the effects of acute postprandial exercise on continuous glucose monitoring (CGM) parameters in individuals with type 2 diabetes mellitus (T2DM), and to identify moderators influencing these outcomes. PubMed and Web of Science were searched until June 20, 2026. Randomized (RCT) and non-randomized (non-RCT) crossover trials examining postprandial exercise in adults with T2DM were included. Seventeen studies met the inclusion criteria. Acute postprandial exercise significantly reduced 24-hour mean glucose (Hedges’ g = -0.30, 95
Type 2 diabetes mellitus (T2DM) complicated by muscle atrophy (diabetic sarcopenia) significantly increases mortality risk, with immunometabolic imbalance-driven disruption of the skeletal muscle microenvironment as a core mechanism. This review focuses on the immune cell–myocyte crosstalk network to elucidate the pathological mechanisms of T2DM-induced muscle atrophy, the local remodeling effects of exercise, and systemic organ crosstalk. In the T2DM state, M1/M2 imbalance and metabolic reprogramming of macrophages, dysregulated mast cell activation and histamine signaling, NLRP3 inflammasome-mediated pyroptosis, T-cell immunosenescence, and chemokine storms collectively disrupt muscle homeostasis. Exercise reverses these abnormalities by downregulating TRIB3/AKT to promote M2 polarization, restoring mast cell function, inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway, increasing Treg infiltration, and downregulating the chemokine network, thereby shifting the local microenvironment from a “pro-inflammatory/destructive” to a “reparative/regenerative” state. Furthermore, exercise exerts systemic regulation through multiple organ axes, including adipose tissue (adipokines and inflammation), gut microbiota, liver (SIRT1/FGF21 signaling), and the brain (hypothalamic-pituitary-adrenal axis and myokines such as BDNF and CTSB for bidirectional neuroimmune regulation). In summary, exercise directly remodels the local immune crosstalk network in skeletal muscle and synergistically improves T2DM-associated muscle atrophy through multi-organ interactions, providing a theoretical basis for precise exercise interventions.
Body composition assessment has traditionally focused on estimating body mass components and the estimation processes required to obtain them in vivo. Within this context, the five-level model and the methodological taxonomy proposed by Wang and colleagues provided a rigorous conceptual framework that has strongly shaped the field. However, contemporary research and practice reveal persistent ambiguity in the use of terms such as direct, indirect, and doubly indirect. This ambiguity has become increasingly evident as methods such as anthropometry and bioelectrical impedance analysis are widely used not only to estimate body mass components, but also to obtain whole-body variables that are directly measured and interpreted as clinically, physiologically, or performance-relevant descriptors. Confusion often arises when directly measured outputs (e.g., skinfolds, girths, phase angle) are not clearly distinguished from model-derived estimates of body composition (e.g., fat mass, fat-free mass). Accordingly, we propose a clarification framework for in vivo body composition assessment that distinguishes: (1) directly measured whole-body variables, (2) model-derived estimates of body composition, and (3) hybrid assessment pathways combining measured and inferred outputs. In this framework, classification depends on the specific variable of interest and the estimation process linking measurement to output, rather than on assigning a fixed label to the instrument itself. The term direct refers only to an output that is measured rather than model-derived, and does not imply direct assessment of body components, greater validity, or superior methodological accuracy. The proposed framework provides a practical conceptual tool for distinguishing measured from estimated body composition outputs, thereby improving methodological transparency, interpretation, and reporting consistency across research and clinical practice.
Family systems are a key influencing factor in the development and maintenance of overweight and obesity in childhood and adolescence with family-based interventions being considered the gold standard in paediatric weight management. So-called second-order level mechanisms, underlying family processes such as communication, parenting skills, and organisational abilities are of particular importance for sustaining family-level behavioural changes and improved health outcomes. This systematic review synthesises interventions that integrate such mechanisms and their impact on health- and weight related outcomes. A systematic literature search was conducted in PubMed, PsycInfo, Web of Science, and the Cochrane Library following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The initial search yielded 16,129 records, after a multistep process including two independent reviewers, n = 22 studies met the final inclusion criteria. Second-order level mechanisms addressed included parenting skills and practices (n = 11), parent–child relationships and communication (n = 6), family functioning and dynamics (n = 4), home and family environment (n = 3), and cultural and family values (n = 3), with several interventions addressing multiple mechanism clusters. n = 9 studies reported significant weight-related changes. Psychosocial and behavioral outcomes, when reported, showed improvements in health-related quality of life, family health routines, nutrition knowledge, and self-efficacy. This systematic review provides an integrative overview of family-based interventions utilising second-order level family mechanisms as structural and relational processes that may support the sustainability of change. The results offer a valuable framework for understanding how families regulate and maintain health behaviours beyond isolated behavioural components.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing global health challenge closely linked to obesity and the metabolic syndrome. This review explores the role of aldosterone as a central contributor to metabolic dysfunction, highlighting its association with adipose tissue dysfunction and systemic insulin resistance which can further influence MASLD development and progression. While aldosterone-related organ damage has been extensively studied in other contexts such as kidney disease, its involvement in MASLD has received less attention. Beyond classical renin-angiotensin-aldosterone system activation, aldosterone secretion can be directly stimulated by leptin and other adipogenic factors, creating a pathogenic link between obesity and metabolic impairment. Aldosterone amplifies chronic inflammation, oxidative stress and insulin resistance, primarily through mineralocorticoid receptor (MR)-dependent mechanisms. These involve both genomic actions regulating pro-inflammatory genes and rapid non-genomic signalling. Additionally, aldosterone MR-independent effects, can further contribute to oxidative stress and inflammatory responses. Significantly, the MR is expressed in liver cells, including hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells. This expression can allow for direct aldosterone-mediated effect on hepatic inflammation, oxidative stress, and fibrosis, which can occur alongside or independently of systemic metabolic pathways. Such direct mechanisms may explain associations found in clinical studies correlating high aldosterone levels -even with low renin- with the prevalence and progression of MASLD. Recognizing aldosterone as a pleiotropic hormone that integrates metabolic and hepatic disease offers new insights into the cardio-kidney-metabolic syndrome and underscores the potential for targeted therapies.
Recently, obesity has exceeded underweight as the more prevalent form of malnutrition among school age children and adolescents globally. This development highlights the importance of understanding the causes and mechanisms through which childhood obesity manifests. Children's weight status - and dietary intake - underlie many influences, including maternal weight status. We aimed to examine how maternal overweight and obesity in a prenatal and a postnatal context influence offspring's dietary intake and their weight status in childhood and adolescence. We searched four databases for studies examining 3- to 17-year-old's dietary intake in relation to maternal weight status. A PRISMA-guided approach was followed to identify all studies eligible to contribute to our questions and 33 studies that met criteria were identified. Data were extracted and analyzed qualitatively, differencing between the temporal context of maternal overweight/obesity and several aspects of the child's dietary intake. Findings were highly heterogenous: Neither of the aspects of dietary intake showed a uniform direction with regards to maternal weight status. There was a tendency to increased adiposity rates among children exposed to postnatal maternal overweight compared to children exposed to prenatal maternal overweight, although the tendency was small. These observations are in line with recent narrative reviews that emphasize the importance of a multitude of factors, rather than the maternal BMI alone, in shaping children's dietary development.
Advanced glycation end products (AGEs), which are glycated forms of proteins and lipids, are increased in diabetes resulting from chronic hyperglycemia. AGEs and their receptor (RAGE) have been linked to cognitive impairment syndromes and may increase the risk of cognitive decline and impairment in people with diabetes who experience chronic hyperglycemia. The objective of this scoping review was to comprehensively document the current evidence concerning the relationship between AGEs and RAGE, measured in the blood, and cognitive function and cognitive impairment syndromes in people with diabetes. MEDLINE, Embase, Cochrane Library, Web of Science Core Collection, APA PsycInfo, and the Psychology and Behavioral Sciences Collection were queried, and the PRISMA Extension for Scoping Reviews guidelines were followed for reporting of methods and results. Twenty-two articles were included in the current scoping review. Among the included articles, we found largely mixed results, whereby both higher and lower levels of AGEs/RAGE were associated with worse cognition or presence of cognitive impairment syndromes in people with diabetes; however, due to notable differences in the methodologies employed to quantify AGEs/RAGE in blood, it is challenging to interpret the factors driving the observed variability. Methodological differences that are likely relevant to AGEs/RAGE quantification include use of plasma vs. serum and selection of AGEs/RAGE studied (e.g., total AGEs/RAGE, pentosidine, carboxymethyl lysine, etc.). Given the observed inconsistencies, currently, there is insufficient evidence to conclude that blood-based AGEs and/or RAGE are indicators of risk for cognitive impairment and decline in people with diabetes. Moreover, it remains undetermined as to which AGEs species or RAGE isoform is most predictive of cognitive impairment or decline in people with diabetes. More studies are needed that include larger sample sizes and well-described and validated methodology to measure AGEs/RAGE.
High-resolution pituitary MRI localises most pituitary neuroendocrine tumours (PitNETs), yet clinically important subgroups remain challenging: (i) very small functioning tumours, particularly corticotroph microadenomas, and (ii) post-operative remnants where scar, gland and tumour cannot be reliably separated. Functional imaging, specifically PET has matured into a problem-solving modality when conventional imaging is equivocal, provided it is used selectively and interpreted within a physiology-led framework. This review proposes an MRI-first, tiered imaging strategy and a pragmatic approach to tracer selection from the available armamentarium ([11C]methionine, [68 Ga]SSTR ligands, [68 Ga]PentixaFor, [18F]FET and [18F]FDG). We emphasise how to optimise PET acquisition and reporting, and how to integrate imaging with endocrine phenotype, treatment history and surgical/radiosurgical planning to maximise clinical impact while safeguarding pituitary function.
Data from current literature have suggested a positive association between Steatotic Liver Disease (SLD) and Chronic Kidney Disease (CKD). In 2023, a consensus of experts suggested that the term metabolic associated steatotic liver disease (MASLD) be used instead of non-alcoholic fatty liver disease (NAFLD), a term that had long been used to indicate the situation of hepatic steatosis not related to alcohol consumption or secondary to another etiology. The majority of hepatologists accepted this suggestion. To critically analyze this described association and compare the impact of change in criteria, we performed a systematic review followed by meta-analysis of incidence studies that evaluated the occurrence of new cases of CKD in patients diagnosed with NAFLD and MAFLD/MASLD. We searched the PubMed, LILACS, SciELO, and Cochrane Library databases for longitudinal studies published through June 2025 that included groups with NAFLD, MAFLD, and/or MASLD, as well as a control group, in the adult population without CKD at baseline. Among 2,099 studies found, twenty met the inclusion criteria. Compared to the patient’s control group, the risk ratio (RR) for incidence of CKD in the group with MAFLD, MASLD, and NAFLD was 1.29 (1.18–1.40), 1.16 (1.12–1.19) and 1.25 (1.14–1.36), respectively. In a new analysis grouping MASLD with MAFLD to assess the impact of the terminology shift, the results remained similar. This review demonstrates that SLD is associated with the risk of developing CKD, regardless of classification. However, this connection needs further elucidation of its mechanisms to comprehend it better and prevent its impact.
Gestational diabetes mellitus (GDM) is defined by maternal hyperglycemia, yet growing evidence indicates that it is a systemic disorder involving oxidative stress, inflammation, endothelial dysfunction and altered placental angiogenesis. The placenta plays a central role in translating maternal metabolic disturbances into fetal and vascular consequences. This narrative review aimed to synthesize current experimental and clinical evidence on the role of oxidative stress and inflammation in the regulation of placental angiogenesis in GDM. The reviewed studies consistently demonstrate that pregnancies complicated by GDM are characterized by increased oxidative stress and inflammatory activity at both systemic and placental levels. These disturbances are associated with endothelial dysfunction and dysregulation of angiogenic signaling, leading to abnormal placental vascular remodeling. Genetic susceptibility primarily influences maternal glucose metabolism, while placental oxidative and angiogenic alterations appear to develop downstream of metabolic stress and are further modulated by epigenetic mechanisms. Collectively, these processes contribute to the characteristic placental phenotype of GDM and may underlie fetal programming and long-term cardiometabolic risk in the offspring. Importantly, evidence from randomized trials and meta-analyses indicates that antioxidant-oriented interventions can partially improve redox balance, inflammatory status, and metabolic indices in women with GDM. Current evidence suggests that oxidative stress may represent a central link between maternal hyperglycemia and placental vascular dysfunction in GDM. Beyond glycemic control, targeting redox imbalance and inflammatory pathways may represent a potential complementary strategy to improve placental function and pregnancy outcomes. Integration of oxidative, inflammatory, and angiogenic biomarkers into future longitudinal studies may facilitate biological stratification of GDM and support the development of more personalized therapeutic approaches.
Hirsutism is a prevalent androgen-dependent condition that significantly affects women’s physical and psychological health. Despite decades of study, major gaps persist in understanding local androgen metabolism, the role of insulin resistance, and individualized treatment responses. This review aims to provide a contemporary update that integrates recent molecular, diagnostic, and therapeutic advances. To critically appraise the current understanding of hirsutism, with an emphasis on: (1) emerging concepts in local androgen action and follicular sensitivity, (2) evolving assessment methods, (3) updated pharmacologic and mechanical treatment options aligned with current endocrine and dermatologic evidence. A narrative review of the literature was conducted in PubMed, Scopus, and Web of Science for studies published between January 2000 and September 2025, using the terms: “hirsutism,” “hyperandrogenism,” “androgen excess,” “idiopathic hirsutism,” “PCOS,” “5α-reductase,” “antiandrogens,” “oral contraceptives,” “laser hair removal,” and “insulin resistance.” Inclusion criteria: human studies, English language, adult females, and peer-reviewed original or review articles. An integrated understanding of systemic and local androgenic activity is transforming the management of hirsutism from a purely cosmetic issue to a complex endocrine disorder with metabolic and psychological dimensions. This review proposes a personalized, multidisciplinary framework that bridges endocrinology, gynecology, and dermatology. Future directions should focus on elucidating local androgen metabolism, tissue-specific enzyme activity, and the role of insulin resistance in idiopathic cases to refine both diagnostic precision and treatment efficacy.
