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Background: Lipedema is a chronic disorder that predominantly affects women and is characterized by abnormal subcutaneous adipose tissue accumulation, pain, and vascular dysfunction. However, reliable circulating biomarkers that reflect disease-specific pathophysiology are still lacking. This study investigated serum markers associated with adipose tissue, inflammation, and angiogenesis to further elucidate the pathophysiology of lipedema. Methods: In this cross-sectional observational study, fasting serum levels of adiponectin, chemerin, lipopolysaccharide-binding protein (LBP), proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble CD163 (sCD163), and soluble CD137 (sCD137)—proteins associated with obesity and inflammation—were measured in 23 premenopausal women with lipedema and 23 age-matched healthy premenopausal controls. Serum endostatin levels, an angiogenesis inhibitor, and insulin-like growth factor binding protein 2 (IGFBP2), a potent proangiogenic factor, were also assessed. Results: Patients with lipedema and obese controls had comparable body mass index, glucose, and serum lipid profiles. No significant differences were observed between groups in circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 and IGFBP2. In contrast, serum endostatin levels were significantly reduced in patients with lipedema (p = 0.038). Additional analyses demonstrated markedly higher endostatin expression in human subcutaneous adipose tissue than in the liver, suggesting that circulating endostatin levels may be related to adipose tissue mass. However, serum endostatin levels were lower in obese compared with normal-weight women (p < 0.001). Conclusion: Lipedema was not associated with altered circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 or IGFBP2. Reduced serum endostatin levels support a potential role for vascular dysfunction in the pathophysiology of lipedema.

Lipedema is a chronic disorder characterized by disproportionate subcutaneous fat accumulation and pain, with an incompletely understood inflammatory component. It remains unclear whether this inflammatory profile is disease-specific or primarily driven by coexisting adiposity. This study aimed to evaluate systemic inflammatory markers in women with lipedema compared with women with obesity and normal-weight controls. This retrospective study included 229 women aged 30-65 years: 78 with lipedema, 76 with obesity without lipedema, and 75 normal-weight controls. Demographic and laboratory data were obtained from medical records. Inflammatory indices, including the neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, C-reactive protein-to-albumin ratio, and C-reactive protein-albumin-lymphocyte index, were calculated. Group comparisons were performed using one-way analysis of variance with appropriate post hoc tests. Age was similar across groups, whereas body mass index was significantly higher in the lipedema and obesity groups than in controls (p<0.001). The erythrocyte sedimentation rate, C-reactive protein level, and CAR were significantly higher in both the lipedema and obesity groups compared with controls, whereas no significant differences were observed between lipedema and obesity groups. The neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, and C-reactive protein-albumin-lymphocyte index did not differ significantly among groups. Inflammatory indices were generally comparable across lipedema grades. These findings suggest that lipedema is associated with low-grade systemic inflammation; however, its inflammatory profile largely overlaps with obesity, indicating shared inflammatory mechanisms rather than a distinct systemic inflammatory phenotype. Among the evaluated markers, C-reactive protein-based parameters, particularly the C-reactive protein-to-albumin ratio, appeared to better reflect inflammatory burden than hematological composite indices.

BACKGROUND: Liposuction is a standard treatment for advanced-stage lipedema, often involving large volumes of tumescent fluid infiltration and aspiration. These shifts raise concerns about postoperative electrolyte imbalances, though systematic data are limited. METHODS: This retrospective single-center study analyzed 116 women with stage 2 or 3 lipedema who underwent liposuction between 2019 and 2023. Pre- and postoperative (within 24 hours) laboratory values including hemoglobin, hematocrit, leukocytes, and electrolytes were compared using paired t-tests, and correlations with clinical variables were assessed. RESULTS: Postoperatively, lower hemoglobin (13.6 ± 0.9 to 11.8 ± 1.2 g/dL, p < .0001) and hematocrit (40.9 ± 2.5 to 35.1 ± 3.5%, p < .0001) levels were observed, alongside higher leukocyte counts (7.6 ± 3.1 to 13.1 ± 5.9 × 109/L, p < .0001). Electrolyte shifts included higher chloride (104.7 ± 2.2 to 106.0 ± 1.9 mmol/L, p < .0001) and slightly lower calcium (2.3 ± 0.1 to 2.2 ± 0.1 mmol/L, p < .0001), sodium (140.8 ± 2.1 to 140.2 ± 2.1 mmol/L, p = .01), and potassium (4.1 ± 0.35 to 4.0 ± 0.4 mmol/L, p = .02). All parameters remained within physiological ranges and were not associated with adverse outcomes. Calcium correlated with hemoglobin (r = 0.49) and hematocrit (r = 0.51) and inversely with aspirate volume (r = -0.41, p = 0.001). CONCLUSIONS: Post-liposuction electrolyte and hematologic changes are mild and clinically insignificant, reflecting predictable hemodilution rather than metabolic disturbance. Routine postoperative testing appears unnecessary for most patients, supporting selective monitoring in those with abnormal baseline values, high aspirate volumes, or relevant comorbidities. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lipedema is a chronic disorder of subcutaneous adipose tissue characterized by disproportionate fat accumulation, pain, and progressive functional impairment, predominantly affecting women. Research remains fragmented across vascular, hormonal, metabolic, and gynecologic perspectives. Recent contributions have advanced specific axes: an international Delphi consensus, a systematic review of hormonal hypotheses, a stromal-vulnerability narrative, and a focused review of adipose biology; but no prior framework has integrated these domains into a single architecture annotated by level of evidence and capable of generating stratified, falsifiable research hypotheses. Here, we propose a hypothesis-generating translational framework that conceptualizes lipedema as the predominant adipose expression of a hormone-sensitive stromal vulnerability. The framework adds a specific molecular convergence axis, ERα/ERβ signaling imbalance interacting with intracrine steroid metabolism (aromatase, 17β-HSDs, AKR1C1), and resolves the disorder into four interacting biological pathways: (i) hormonal transition sensitivity across the female life course; (ii) metabolic– behavioral amplification; (iii) gynecologic–endocrine comorbidity; and (iv) intrinsic stromal–adipose susceptibility. The framework predicts that lipedema and its cognate expressions in hormone-responsive tissues (including gynecologic disease, connective tissue laxity, microvascular dysfunction, neurosensory amplification, and neuropsychological burden) may share a common stromal-endocrine substrate while preserving phenotypic specificity through dominant-pathway combinations. Four features distinguish this framework from prior syntheses: (a) ERα/ERβ signaling imbalance is articulated as a candidate molecular convergence axis linking adipose, gynecologic, connective-tissue, microvascular, and neuro-immune manifestations; (b) intracrine steroid metabolism (aromatase, 17β-HSDs, AKR1C1) is incorporated as the mechanistic anchor of stromal hormone-responsiveness; (c) per-component evidence-level annotation is applied throughout (Level 1A/1B: direct evidence in lipedema; Level 2: observational association; Level 3: mechanistic extrapolation); and (d) stratified, falsifiable research hypotheses are derived from dominant-pathway phenotypes. Two domains, metabolic burden and steroid signaling, emerge as promising translational research domains. Important limitations apply. Direct mechanistic evidence in lipedema-specific tissues is limited; much of the supporting biology is extrapolated from adipose, gynecologic, and metabolic literatures; and most clinical data derive from observational cohorts in referral centers. This article therefore proposes a hypothesis-generating translational framework, not a clinical guideline or therapeutic recommendation.

ObjectivesThere is a deficiency in awareness and knowledge of lipedema disease among the general public and healthcare professionals. This situation may lead patients to waste time on getting the correct diagnosis and treatment. Currently, information regarding women's awareness and knowledge level of lipedema in Turkey is limited. This study aims to examine women's awareness, knowledge level, and desire for information concerning lipedema in Turkey.MethodsA total of 502 volunteer women participated in this online cross-sectional survey study. The survey, constructed by the authors of the study with the assistance of guidelines, systematic reviews, and current literature, consisted of sections aimed at determining demographic data, lipedema awareness, knowledge level, lipedema symptoms and suspicion, as well as individuals' health behavior and desire for information. The primary outcome of the study was lipedema awareness, which was defined by having previously heard the term lipedema.ResultsDespite 76.1% of participants reporting awareness of lipedema, the average knowledge score about the condition was a low-to-moderate level of knowledge. The vast majority of participants (71.3%) indicated that they were willing to learn more about lipedema, and their preferred source of information was healthcare professionals (80.3%). Yet, only 19 participants (3.8%) think that lipedema is sufficiently regarded within the healthcare system.ConclusionThis study reveals that, despite relatively high awareness of lipedema among women in Turkey, the level of knowledge remains limited. The strong willingness to receive further knowledge and the preference for healthcare professionals as the principal source of information garner attention. However, the low confidence in the recognition of lipedema within the healthcare system may suggest that healthcare professionals have insufficient knowledge or do not prioritize this issue. Improving awareness and knowledge of lipedema among the public and healthcare professionals might facilitate early identification and minimize treatment delays.

BACKGROUND: Lipedema is a prevalent chronic condition in women, characterized by a painful and symmetrical accumulation of adipose tissue primarily in the lower limbs. Its diagnosis is based on specific clinical characteristics; however, these characteristics lack robust scientific validation. Furthermore, lipedema is frequently misdiagnosed as obesity. This study aims to compare quality of life and physical and psychological characteristics between patients with obesity with and without lipedema. METHODS: This cross-sectional study included 30 patients with obesity and lipedema (Lip-Obes group) and 29 patients with only obesity (nonLip-Obes group). Quality of life, body composition (BMI, fat free mass, fat mass, waist-to-hip ratio, waist-to-height ratio, leg volume), pain (pain pattern, pressure pain thresholds, pain interference, pain distribution, symptoms of neuropathic pain), physical functioning (hand grip strength, quadriceps strength, functional exercise capacity, functional mobility and physical activity level), and psychosocial functioning (pain catastrophizing, depression, anxiety, and stress, body image dissatisfaction, self-efficacy, and eating difficulties) were assessed using clinical measurements and self-reported outcomes. Statistical analyses were performed using independent t-tests or Mann-Whitney U tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables. A two-sided p-value of < 0.05 was considered statistically significant. RESULTS: Compared to the nonLip-Obes group, the Lip-Obes group showed greater impairments in quality of life (p < 0.05). Despite similar body composition variables, the Lip-Obes group had lower waist-to-hip, waist-to-height, upper leg-to-waist, and lower leg-to-waist ratios, as well as higher total limb volume than the nonLip-Obes group. Additionally, the Lip-Obes group reported higher pain intensity, lower pressure pain thresholds in the arms and legs, and greater pain interference than the nonLip-Obes group (p < 0.05). Although hand-grip strength and physical activity levels were comparable, the Lip-Obes group exhibited lower quadriceps strength, functional exercise capacity, and functional mobility (p < 0.05). Additionally, the Lip-Obes group reported higher pain catastrophizing, greater body image dissatisfaction, and more severe eating difficulties than the nonLip-Obes group (p < 0.05). No significant differences were found in depression, anxiety, stress, or self-efficacy between groups (p > 0.05). CONCLUSION: This cross-sectional study highlights the complex nature of lipedema, providing preliminary evidence of differences in quality of life and distinct body composition and physical and physiological characteristics between patients with obesity with and without lipedema. These results emphasize the need for further research to identify diagnostic biomarkers for lipedema through in-depth investigations. Future studies should also focus on developing and optimizing a multidisciplinary treatment approach tailored to the unique characteristics of patients with lipedema.

INTRODUCTION: Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat deposition, pain, and progressive functional impairment. Although diagnosis remains primarily clinical, ultrasound has emerged as a valuable adjunctive tool for diagnosis, surgical planning, intraoperative guidance, and postoperative monitoring. The aim of this review was to provide a comprehensive overview of the current and potential applications of ultrasound throughout the entire surgical management pathway of patients with lipedema. MATERIALS AND METHODS: A narrative review of the literature was conducted using PubMed/MEDLINE, Scopus, and Google Scholar databases. Articles published up to January 2026 were screened using the keywords "lipedema," "lipoedema," "ultrasound," "ultrasonography," "lipedema diagnosis," "lipedema imaging," "lipedema surgery," and "liposuction." Studies addressing ultrasound-based diagnosis, differential diagnosis, surgical planning, intraoperative guidance, and postoperative monitoring in lipedema patients were included. Both original investigations and review articles published in English were considered. RESULTS: Ultrasound demonstrated significant utility across all phases of lipedema management. In the preoperative setting, it improved diagnostic accuracy by identifying characteristic sonographic features, quantifying tissue thickness, differentiating lipedema from obesity and lymphedema, and enabling vascular mapping for surgical safety. Advanced techniques, including three-dimensional ultrasound, provided additional information regarding fascial alterations, fibrosis, and fluid accumulation. Intraoperatively, ultrasound off ered real-time visualization of anatomical structures, facilitated identification of fibrotic tissue, and supported more precise liposuction by improving cannula guidance andassessment of tissue homogeneity. Postoperatively, ultrasound enabled early detection of complications such asseromas and hematomas, assessment of fi brosis and tissue remodeling, and long-term monitoring of disease recurrence or progression. DISCUSSION: The available evidence suggests that ultrasound represents a versatile, accessible, and reproducible imaging modality capable of enhancing both diagnostic and surgical aspects of lipedema care. By integrating ultrasound intopreoperative evaluation, intraoperative decision-making, and postoperative follow-up, clinicians may improve surgical precision, patient safety, and treatment outcomes. Nevertheless, the current literature remains limited by heterogeneity, operator dependency, and the absence of standardized imaging protocols. Larger multicenter studiesare needed to validate diagnostic criteria and establish evidence-based guidelines for ultrasound utilization in lipedema management. CONCLUSION: Ultrasound has the potential to become an integral component of modern lipedema management. Its applications extend beyond diagnosis to encompass surgical planning, intraoperative guidance, and postoperative surveillance. The increasing availability of portable, high-resolution ultrasound devices may further facilitate its routine incorporation into clinical practice, ultimately contributing to safer procedures, more personalized treatment strategies, and improved long-term outcomes for patients with lipedema. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

OBJECTIVE: To compare central sensitization (CS), pressure pain threshold (PPT), and psychosocial factors between women with lipedema and healthy controls and to identify variables associated with CS in lipedema. METHODS: In this cross-sectional study, 30 women with clinically diagnosed lipedema and 30 age-matched healthy controls were assessed.CS was measured with the Central Sensitization Inventory (CSI), and PPT was recorded bilaterally at the deltoid, lateral thigh, and medial knee using an algometer, pain-related cognitions with the Pain Catastrophizing Scale (PCS), and mood with the Hospital Anxiety and Depression Scale (HADS). RESULTS: Compared with controls, the lipedema group had lower PPTs at all sites (all p ≤ 0.001) and higher CSI scores (p ≤ 0.001). CS prevalence (CSI ≥ 40) was 70.0% in lipedema versus 23.3% in controls (p≤ 0.001). HADS-Depression (p = 0.001), HADS-Anxiety (p = 0.017), and PCS helplessness, magnification, rumination, and total scores (all p ≤ 0.006) were higher in lipedema. In the total sample, CSI correlated negatively with all PPT values (all p ≤ 0.003) and positively with HADS-Depression/Anxiety and PCS scores (all p < 0.001). In multivariable analysis among patients with lipedema, higher CSI was associated with greater BMI (β = 1.117, p=0.018), hypertension (β = 15.918, p = 0.009), diabetes mellitus (β = 16.663, p = 0.002), higher VAS pain (β = 0.368, p = 0.002), lower right medial knee PPT (β = - 3.891, p = 0.011), and higher HADS-Depression (β = 1.307, p = 0.038). CONCLUSIONS: Lipedema is associated with lower pain thresholds and higher CS, alongside greater depressive and anxiety symptoms and pain catastrophizing. CS in lipedema appears linked to pain intensity, depressive symptoms, and cardiometabolic comorbidities. These findings suggest that management should complement peripheral approaches with strategies targeting central pain mechanisms and psychosocial factors. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lipedema is a chronic, painful, estrogen-sensitive disorder of subcutaneous adipose tissue whose persistence is poorly explained by linear cause-effect models. Patients, clinicians and affected relatives frequently report that symptom flares track periods of sustained psychological stress, yet the 2026 international Delphi consensus records no formal role for stress, and a controlled study found normal stress scores with no stress-pain association, leaving the observation unexplained and exposed to a stigmatizing reading. We propose that lipedema chronicity is better understood as a self-sustaining attractor of a neuroimmune-stress feedback loop than as the product of any single root cause. In the proposed circuit, sustained hypothalamic-pituitary-adrenal and sympathetic activation promotes adipose mast-cell mediator release, neurogenic inflammation (CGRP, NGF), sensitization, pain and distress, which feed back onto the stress axis; genetic predisposition and estrogen act as the constraint landscape rather than as linear causes. We formalize the loop as a low-dimensional dynamical system with saturating feedback and a slow, near-irreversible tissue-remodeling variable. The model exhibits bistability above a critical loop gain and hysteresis, recasting the acute-to-chronic transition as a saddle-node bifurcation and chronicity as a high-burden basin maintained by a fibrotic ratchet. It yields falsifiable predictions-flare hysteresis, estrogen as a bifurcation parameter, a stage-dependent reversibility window, and super-additive combination therapy-and an explicit, non-stigmatizing map of which weak causal edges to measure. It reframes early, multimodal intervention as leverage on a loop rather than treatment of a symptom.

Lipedema is a chronic and underrecognized adipose tissue disorder in women, often misdiagnosed as obesity or lymphedema. Diagnosis is challenging due to overlapping clinical features and the lack of standardized imaging criteria. We report a 50-year-old postmenopausal woman, known hypothyroid on thyroxine and currently euthyroid, presenting with a 6-year history of progressive, symmetrical bilateral lower-limb swelling, predominantly involving the thighs and legs with sparing the feet. Body mass index was 37.8 kg/m2 (Class II obesity). Lower-limb Doppler ultrasonography excluded arterial or venous obstruction, and filarial serology was negative. Crucially, lymphoscintigraphy, a cost-effective and readily available nuclear medicine tool, demonstrated normal lymphatic drainage, excluding lymphedema and prompting whole-body dual-energy X-ray absorptiometry (DEXA) for further assessment. Whole-body DEXA revealed obesity with disproportionately increased and symmetrical lower limb fat, elevated fat mass index (16.7 kg/m2), and near-equal trunk-to-leg fat distribution, suggestive of a possible lipedema phenotype (Stage II). Magnetic resonance imaging showed extensive symmetrical fat signal intensity in the subcutaneous layer, supporting the DEXA findings. This case emphasizes the sequential role of nuclear medicine techniques—lymphoscintigraphy for functional lymphatic assessment and DEXA for quantitative body composition analysis—in the accurate diagnosis of lipedema, in an obese postmenopausal woman.

ObjectiveLipedema, which mainly affects women, is a chronic and progressive disorder characterized by abnormal adipose tissue accumulation in the limbs. Despite its clinical importance, research on lipedema remains limited. Bibliometric analysis provides a quantitative way to evaluate the literature, identify trends, and assess research impact.Materials and methodsGlobal lipedema research was analyzed in the Web of Science database using the terms "lipedema", "lipoedema", and "lipolymphedema" for publications indexed through March 2025. Articles were classified by publication type, year, country of origin, journal quartile, and citation count. Citation analyses excluded publications from 2024 and 2025 because citation accumulation was incomplete. Only English original articles and reviews were included, while editorials, meeting abstracts, and non-indexed sources were excluded.ResultsOf 610 records identified, 382 met the inclusion criteria. The analysis identified the main contributing countries and highlighted knowledge gaps and opportunities for multidisciplinary collaboration in the evolving field of lipedema research.ConclusionsThis study provides a global overview of lipedema-related research and its scholarly development. It also highlights the need for further studies on the pathophysiology, diagnosis, and treatment of lipedema.

BACKGROUND/AIM: Although various distinctive morphological features such as hyperproliferation of adipocytes, fibrosis, and inflammation have been described in the progression of lipedema, the underlying mechanisms of these changes are not yet fully understood. In this study, we aimed to investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW) to demonstrate the role of inflammation in lipedema. METHODS: The retrospective study consisted of 60 lipedema patients (Group 1) and 40 healthy controls (Group 2). The age, height, weight, and body mass index (BMI) of all participants were recorded, along with the lipedema type and stage for Group 1. Laboratory results, including complete blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were obtained for all participants. Hemoglobin, leukocyte, lymphocyte, neutrophil, and platelet counts, NLR, PLR, MPV, PDW, CRP, and ESR were evaluated. RESULTS: The mean age was 45.45 ± 10.17 years in Group 1 and 44.90 ± 10.69 years in Group 2; the BMI was 32.15 ± 5.05 in Group 1 and 30.94 ± 4.98 in Group 2, with no significant difference between the groups (p > 0.05). The most common type was Type 2 lipedema. Platelet counts, CRP, NLR, and PLR levels were significantly higher in Group 1 than in Group 2 (p < 0.05). There was no difference between groups in MPV and PDW values (p > 0.05). There was a positive correlation between BMI and both leukocyte count and CRP levels (p < 0.05). CONCLUSION: In our study investigating inflammation in lipedema-an etiology that is still not fully understood-NLR, PLR, platelet count, and CRP levels were found to be significantly higher in the patient group. The increase in BMI was correlated with leukocyte count and CRP levels. This finding is important for elucidating the etiopathogenesis of the disease, and we believe it may guide future research in this area.

ObjectivesLipedema is a chronic disorder characterized by pain and disproportionate fat distribution, and its diagnosis is frequently overlooked. The aim of this study was to evaluate and compare the responses generated by contemporary artificial intelligence models-ChatGPT-5o, Gemini-3, and Perplexity AI-to structured clinical questions developed in accordance with the 2024 S2k Lipedema Guideline. The models were analyzed in terms of clinical accuracy, readability, and reference reliability to assess their performance in delivering guideline-based medical information.MethodsThis cross-sectional and comparative study was conducted by submitting 30 structured clinical questions, prepared on the basis of the relevant guideline, to three large language models. Responses collected on 10 February 2026, were evaluated using a seven-point Likert scale (reliability) and a five-point scale (accuracy). Text readability was assessed using six established indices, including the Flesch Reading Ease Score (FRES), Flesch-Kincaid Grade Level (FKGL), and Gunning Fog Index (GFOG). Reference reliability was examined by analyzing hallucination tendencies as defined in the literature.ResultsA statistically significant difference in reliability was observed among the models (p = .041); Perplexity (4.95 ± 1.20) achieved significantly higher scores than ChatGPT-5o (4.38 ± 1.05) (p = .038). In readability analyses, Perplexity (12.80 ± 2.10) required a significantly higher educational level according to FKGL scores compared to both ChatGPT-5o (p = .041) and Gemini-3 (p = .036). Regarding reference reliability, ChatGPT-5o outperformed Perplexity in source verifiability (p = .031), bibliographic precision (p = .044), and total RHS scores (p = .027), emerging as the most robust model in this domain. No statistically significant differences were found among the models in terms of clinical accuracy and usefulness (p > .05). Inter-rater agreement was excellent (Kappa: 0.92-0.97).ConclusionIn this study, ChatGPT-5o distinguished itself in reference quality, whereas Perplexity demonstrated superior reliability. However, the complex linguistic structures accompanying efforts to maintain high medical accuracy may constitute a significant barrier for individuals with limited e-health literacy. Although these systems show strong potential as medical information resources, they cannot yet replace expert physician oversight in terms of patient safety. A balanced approach between technical reliability and patient-centered simplification remains necessary.

Background:Lipedema is a chronic connective tissue disorder characterized by painful subcutaneous adipose accumulation, mainly in the lower extremities. Pain is a hallmark feature, yet its mechanisms remain poorly defined. Neuropathic components may contribute, but direct comparisons with lymphedema are scarce.Methods:In this exploratory cross-sectional study, 118 female patients with lipedema (n = 62) or bilateral lower extremity lymphedema (n = 56) were assessed. Pain intensity was measured with the Visual Analogue Scale (VAS). Neuropathic pain was evaluated with painDETECT and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS). Psychological status was measured using the Hospital Anxiety and Depression Scale (HADS), cognitive–emotional aspects with the Pain Catastrophizing Scale (PCS), and health-related quality of life with the WHOQOL-BREF.Results:Lipedema patients reported higher pain severity (VAS 6.2 ± 1.4 vs. 5.5 ± 1.5, p = 0.02) and greater neuropathic pain prevalence (42% vs. 21%, p < 0.01) than lymphedema. painDETECT and LANSS scores were significantly higher in lipedema (p < 0.001). HADS-Anxiety (10.2 ± 3.8 vs. 7.8 ± 3.5, p = 0.005) and PCS scores (29.5 ± 7.2 vs. 25.4 ± 6.5, p = 0.03) were also elevated, while HADS-Depression was slightly higher in lymphedema without significance. WHOQOL-BREF scores were similarly reduced in both groups compared to population norms. Correlation analyses showed strong associations between pain intensity, neuropathic features, catastrophizing, and anxiety, particularly in lipedema.Conclusions:A substantial proportion of lipedema patients exhibit neuropathic pain features and higher pain severity compared with lymphedema, while anxiety and pain catastrophizing appear to amplify symptom burden; however, quality-of-life impairment is substantial in both conditions, and the findings should be interpreted as hypothesis-generating with implications for more individualized management approaches.

BACKGROUND: Recent studies have consistently shown that patients with lipedema are at a higher risk for depression and anxiety. The aim of this study is to identify the psychological factors associated with lipedema syndrome (LS) and their link to the patient's psychological symptomatology. METHODS: A mixed-methods approach was employed, combining quantitative and qualitative components. The quantitative component involved anonymous online questionnaires, including a Health and Demographic Questionnaire, the body satisfaction and global self-perception questionnaire (BSGSPQ), the lymphedema quality of life questionnaire (LYMQOL), and the Hospital Anxiety and Depression Scale (HADS). The qualitative component consisted of oral interviews to explore the complexity of the phenomenon. Participants included those with "easy bruising," a waist-to-hip ratio ≤0.7 (W/H), and pain levels ≥4/10 on the visual analogue scale (VAS). RESULTS: Our findings indicate that the level of depression is positively correlated with spontaneous pain (p = 0.002; r = 0.331) and the lack of medical understanding (p = 0.011; r = 0.229). Anxiety scores are inversely correlated with body satisfaction (r = -0.317) and global self-perception (r = -0.393); similarly, depression scores show similar correlations with body satisfaction (r = -0.445) and global self-perception (r = -0.608), all with p value of <0.0001. DISCUSSION AND CONCLUSION: This study highlights significant connections between the physical symptoms and mental health in patients with LS. The more affected the self-perception, the greater the depression and anxiety levels. These multiple contributing factors may explain the decline in quality of life (QOL) and deterioration of mental health. It is therefore crucial to proactively integrate mental health management into the care of LS patients. Future research should focus on identifying concrete, actionable methods to support women experiencing LS.

Lipedema is a chronic adipose tissue disorder characterized by disproportionate and often painful enlargement of the extremities, occurring predominantly in women. Despite increasing clinical recognition, the underlying pathophysiology remains incompletely understood and is likely multifactorial. Existing evidence suggests contributions from vascular alterations, adipose tissue remodeling, inflammatory activation, hormonal influences, and lymphatic dysfunction. This review proposes a hypothesis-generating integrative framework in which lipedema may reflect a regenerative imbalance of subcutaneous adipose tissue. Within this model, genetically and hormonally modulated endothelial permeability could promote activation of perivascular adipose-derived stromal/stem-cell niches and stromal vascular fraction signaling pathways, thereby facilitating coupled angiogenesis and adipogenesis. Progressive adipocyte hyperplasia and hypertrophy may subsequently contribute to inflammatory remodeling, pain generation, and secondary impairment of dermal and subdermal lymphatic drainage. The proposed framework attempts to integrate clinical, histological, imaging, molecular, and endocrine observations into a biologically coherent conceptual model. At the same time, the review emphasizes the current limitations of the available evidence, the heterogeneity of lipedema phenotypes, and the ongoing controversies regarding disease progression, obesity overlap, and the relative role of lymphatic dysfunction. Finally, the potential mechanistic rationale of lymphatic-sparing liposuction is discussed in the context of tissue decompression, restoration of lymphatic transport, and interruption of persistent adipose remodeling. The model presented here should be interpreted as a hypothesis-generating conceptual scaffold requiring prospective validation. Importantly, the present framework should be interpreted as a biologically plausible and hypothesis-generating conceptual model rather than a definitive mechanistic doctrine. Several proposed interactions remain associative and require prospective biological validation.