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Background: Lipedema is a chronic, progressive adipose tissue disorder that almost exclusively affects women,characterized by bilateral, disproportionate subcutaneous fat accumulation in the limbs, pain, easy bruising, andresistance to conventional weight-loss interventions. Because its appearance is frequently mistaken for obesity,women with lipedema are exposed to prolonged misdiagnosis, weight stigma, and inadequate healthcareresponses. The psychological, psychosocial, and behavioral burden of the condition is increasingly recognized,but the evidence is fragmented across clinical, psychological, and eating-related research. Objective: To synthesize the available evidence on the psychological, psychosocial, and behavioralconsequences of lipedema in adult women — including psychological distress, anxiety and depression, pain andfunctional impact, delayed diagnosis, weight stigma, body image, shame, emotion regulation, quality of life, andeating-related outcomes — and to organize this evidence within an explicit biopsychosocial framework. Methods: A structured narrative review following SANRA principles and incorporating applicable PRISMA2020 elements was conducted. Databases targeted included PubMed/MEDLINE, Embase, Scopus, Web of Science, PsycINFO, and the Cochrane Library; a complete PubMed search strategy is reported. Observational,qualitative, mixed-methods, longitudinal, and relevant intervention studies and reviews of adult women withclinically diagnosed lipedema and separately identifiable lipedema data were eligible. Data were extracted intostandardized tables, appraised for methodological quality, and synthesized thematically by domain. Each findingwas classified as direct evidence (lipedema populations), indirect evidence (related populations such as obesity,chronic pain, lymphedema, or weight-stigma research), or hypothesis (theoretical mechanisms not directlydemonstrated). Results: Thirty-six sources formed the evidence base. Direct evidence documents substantially reducedhealth-related quality of life across physical, emotional, and social domains, elevated prevalence of depressivesymptoms, and frequent experiences of weight stigma, shame, and body-image disturbance. Pain and functionallimitations are nearly universal and are associated with disability, kinesiophobia, and reduced activity. Emotionregulation difficulties and coping styles characterized by depressive processing are reported. Eating-disorderscreening indicators are elevated in preliminary samples, and clinically diagnosed binge-eating disorder waspresent in 14.7% of patients in one specialist pilot cohort. Direct evidence for compensatory behaviors andcompulsive exercise in lipedema was not identified. Conclusions: Distress, stigma, body image concerns, and impaired quality of life are the relativelybetter-documented psychological consequences of lipedema. Emotion regulation, eating-disorder risk, anddysfunctional eating behaviors remain less studied and methodologically heterogeneous. A biopsychosocialmodel — in which pain, functional limitation, delayed diagnosis, and stigma converge on body image, emotionregulation, eating behavior, and quality of life — is supported by converging direct and indirect evidence,although most links remain associative rather than causal. Multidisciplinary, non-stigmatizing, individualizedcare is warranted.

Introduction: Low-carbohydrate diets (LCDs) have been suggested as a potential treatment option for females with lipedema, due to their superiority in reducing pain, possibly through improvements in insulin dynamics. Objectives: The objective of this secondary analysis was to compare changes in markers of glucose and insulin dynamics after a low-carbohydrate versus low-fat low-energy diets in females with lipedema and obesity. A secondary objective was to investigate potential associations between changes in glucose and insulin dynamics and changes in pain.Methods: Females with obesity and lipedema were randomized to either an LCD or a low-fat low-energy diets (1200 kcal/day for both; 75 vs. 180 g carbohydrates/day) for 8 weeks. Basal and postprandial (total and incremental area under the curve (tAUC and iAUC)) concentrations of glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), and C-peptide were measured before and after the intervention, and HOMA-IR, Matsuda index and insulin clearance calculated.Results: A total of 70 females (35 in each group, age 47 ± 11 years, BMI 37 ± 5 kg/m2) were included in the analysis. Both groups lost body weight, but with a significantly greater weight loss in the LCD group. Both groups showed ed a reduction in basal glucose, C-peptide, and insulin concentrations, with a greater reduction in glucose on the LCD. A significant increase in glucose iAUC, C-peptide iAUC, insulin clearance, and Matsuda index was observed in the LCD group only. Both groups experienced an increase in GIP tAUC, as well as a reduction in HOMA-IR, with no significant differences between groups. No associations were seen between changes in glucose and insulin measures and changes in pain.Conclusion: Both diets improved insulin dynamics in females with lipedema and obesity, despite additional benefits in the LCD group. However, changes in the measured indices of insulin dynamics were not associated with pain reduction, suggesting that the effects of the LCD on pain and systemic metabolic regulation may involve other pathways.

Lower extremity swelling has a broad differential diagnosis, including lymphedema, obesity-induced lymphedema, phlebolymphedema, and lipedema. Although these conditions may appear similar clinically, their pathophysiology and lymphoscintigraphic findings differ. Obesity, venous insufficiency, and abnormal adipose tissue can complicate image interpretation. We present four representative cases to illustrate characteristic imaging patterns across these conditions. These cases highlight the importance of interpreting lymphoscintigraphy in a clinical context.

Hyperechoic subcutaneous nodules in lipedema may mimic angiolipomas but represent an inflammatory and hypoxic-ischemic process rather than a neoplasia, despite tissue expansion. As the painful nodules expand, biopsy is recommended to exclude cancer. In this context, ultrasound (US) has become a pivotal tool for diagnosing and managing these nodules when combined with histopathologic assessment. However, many professionals in the field still have limited knowledge of this topic. In the present case series, the US and histopathologic findings of hyperechoic nodules in two patients with lipedema were compared with those observed in two patients with angiolipoma, with the aim of proposing US criteria to distinguish between these entities and highlighting the importance of accurate differential diagnosis.

ObjectiveThis study aimed to investigate central sensitization (CS) in individuals with lipedema using pressure pain threshold measurements and to examine its relationship with clinical features, sonographic findings, body composition, and Central Sensitization Inventory (CSI) scores.MethodsA total of 61 female patients with lipedema and 20 healthy controls were included in this cross-sectional study. Pressure pain threshold (PPT) was assessed at the thigh, pretibial region, and forearm using a manual algometer. Sonographic subcutaneous fat thickness was evaluated, and body composition parameters were assessed using bioelectrical impedance analysis. Clinical outcomes related to CS-including the CSI, Visual Analog Scale (VAS), Lower Extremity Functional Scale (LEFS), Short Form-12 (SF-12), and the Extended Nordic Musculoskeletal Questionnaire (NMQ-E)-were recorded. Linear mixed-effects models were used to compare PPT across groups, anatomical sites, and disease stages. Associations between PPT, CSI scores, body composition parameters, sonographic findings, and clinical measures were evaluated using Pearson correlation analyses.ResultsPatients with lipedema exhibited significantly lower PPT values across all anatomical regions, including the forearm, and significantly higher CSI scores compared with healthy controls (p < .001). Sonographic assessment confirmed increased subcutaneous fat thickness in the lower extremities of lipedema patients. Lipedema stage was not associated with overall PPT levels. However, lower forearm PPT and LEFS scores were observed in more advanced stages. Forearm PPT showed significant negative correlations with lean body mass, body fat mass, and total body water (p < .05), while no other significant associations were identified.ConclusionIndividuals with lipedema demonstrate features consistent with CS, characterized by reduced PPTs in both affected and non-affected regions together with elevated CSI scores. These findings suggest that altered pain processing may contribute to the widespread pain and functional limitations observed in lipedema, highlighting the importance of comprehensive assessment of CS in this population.

Objective: Lipedema is a chronic adipose tissue disorder characterized by bilateral and symmetrical subcutaneous fat accumulation, predominantly affecting women. Because it is frequently confused with obesity and lymphedema, diagnosis may be delayed. This proof-of-concept study aimed to evaluate the feasibility of LipoAssist, a structured GPT-4–based clinical workflow designed for the preliminary assessment of lipedema under simulated conditions. Methods: Ten simulated clinical scenarios representing lipedema and relevant differential diagnoses were evaluated using LipoAssist. The workflow was designed to obtain a structured medical history, assess clinically relevant symptoms, and generate a standardized case summary. Three board-certified Physical Medicine and Rehabilitation specialists independently evaluated the AI-generated outputs using a 5-point Likert scale across six criteria. A total of 180 ratings were analyzed. Inter-rater agreement was assessed using the intraclass correlation coefficient and Kendall's coefficient of concordance. Results: The overall mean performance score was 3.55 ± 0.64. The highest scores were observed for correct understanding of the clinical condition (4.63 ± 0.49) and identification of the most likely diagnosis (4.53 ± 0.51). Lower scores were recorded for recommendations regarding further diagnostic evaluation (2.17 ± 0.83) and assessment of surgical necessity (1.93 ± 0.64). Case-summary clarity and adequacy of history taking received mean scores of 3.87 ± 0.63 and 3.73 ± 0.64, respectively. Inter-rater agreement was good (ICC = 0.82; 95% CI: 0.68–0.91), and Kendall's W was 0.79. Conclusion: LipoAssist demonstrated promising performance in structured history taking, organization of clinical information, and identification of the most likely diagnosis in simulated lipedema scenarios. However, its performance was limited in advanced diagnostic recommendations and surgical decision-making. These findings support the feasibility of a structured GPT-4–based workflow under simulated conditions but do not establish clinical validity, diagnostic accuracy, or readiness for routine implementation.

OBJECTIVE: To evaluate ultrasonographic changes in lower extremity tendons and plantar fascia of patients with chronic edema and their relationship with edema volume, pain, function, and quality of life. DESIGN: This observational case-control study included 53 patients with chronic lower extremity edema and 55 age- and sex-matched controls. Ultrasonography assessed the Achilles, tibialis posterior, peroneal, and patellar tendons and plantar fascia. Edema volume was calculated from limb circumferences. Outcomes included the Lower Extremity Functional Scale (LEFS), Lymphedema Quality of Life Questionnaire-Leg (LYMQOL-Leg), and Visual Analogue Scale (VAS). RESULTS: All tendons (except the patellar tendon) and plantar fascia were thicker in the edema group than controls ( P <0.05). Differences in Achilles tendon and plantar fascia thickness remained significant after BMI adjustment (all P <0.01) and correlated positively with edema volume ( P <0.05). Plantar fasciitis (50.9%) and Achilles tendinopathy (22.6%) were more frequent in the edema group ( P <0.05). Patients had lower LEFS and higher LYMQOL-Leg and VAS scores (all P <0.01). CONCLUSION: Chronic lower extremity edema was associated with alterations in tendon and fascial morphology, particularly the Achilles tendon and plantar fascia. Musculoskeletal ultrasonography may complement clinical evaluation by providing information regarding tendon and fascial involvement.

BACKGROUND: Lipedema is a chronic adipose tissue disorder primarily affecting women, characterized by abnormal fat accumulation, pain, and reduced mobility. Its impact on sexual function remains underexplored. This study aimed to evaluate sexual function in women with lipedema and examine its associations with anxiety, depression, lower extremity function, and quality of life. METHODS: In this cross-sectional study, 100 sexually active women were recruited: 50 with lipedema and 50 age- and Body Mass Index-matched healthy controls. Sexual function was assessed with the Female Sexual Function Index (FSFI); anxiety and depression with the Hospital Anxiety and Depression Scale (HADS-A and HADS-D); quality of life with the EuroQOL 5-Dimensional 5-Level (EQ-5D-5L) instrument; lower extremity function with the Lower Extremity Functional Scale (LEFS); and pain intensity with the Visual Analog Scale (VAS). Multiple linear regression analysis was conducted to identify the factors associated with the total FSFI score. RESULTS: Women with lipedema had significantly lower total FSFI scores compared to controls (21.58 ± 3.99 vs. 25.86 ± 3.21, P < .001), with 76% having FSFI scores below the cut-off (≤ 26.55) compared to 36% of controls. All FSFI domain scores were significantly lower in the lipedema group (all P < .05). In the lipedema group, there was a significant correlation between total FSFI scores and age (P = .002), pain intensity (VAS; P = .022), depression (HADS-D; P = .010), quality of life (EQ-5D-5L index; P = .027), and lower extremity function (LEFS; P < .001). Multiple linear regression analysis identified depression (HADS-D; P = .047), perceived health status (EQ-5D-5L VAS; P = .033), and lower extremity function (LEFS; P = .011) as independent variables that had a significant relationship with the total FSFI score. DISCUSSION: Lower sexual function is common among women with lipedema and is associated with anxiety and depressive symptoms, lower extremity function, and pain intensity. These findings highlight the importance of incorporating sexual function assessment into the routine evaluation of patients with lipedema and support the need for comprehensive multidisciplinary treatment approaches addressing physical, psychological, and sexual health aspects of care.

BACKGROUND: Lipedema is a chronic disorder characterized by excessive, bilateral, and symmetrical deposition of subcutaneous adipose tissue, predominantly in the lower extremities. Despite its prevalence, lipedema is frequently misdiagnosed as lymphedema, and lymphoscintigraphy is commonly used to differentiate between the two. This systematic review synthesizes the available evidence regarding the most common lymphoscintigraphy findings in patients with lipedema. METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was performed across the MEDLINE/PubMed, Embase, and Web of Science databases. Studies were included if they reported lymphoscintigraphy findings in patients with lipedema and provided a clear description of the imaging protocol. Extracted data included patient demographics, lymphoscintigraphy protocols, and imaging findings. RESULTS: Seven studies met the inclusion criteria, encompassing 470 patients, of whom 311 had lipedema. The mean age was 47.4 years, and all patients were women. The mean body mass index was 32.6 kg/m2. Lymphoscintigraphy findings were normal in 61.4% of patients with lipedema. Tortuous lymph vessels were the most common abnormality (56.8%), followed by collateral lymph vessels (49.1%) and popliteal node visualization (44.0%). Dermal backflow (3.8%) and secondary lymphedema (11.8%) were less frequent. CONCLUSIONS: Lymphoscintigraphic alterations in patients with lipedema seem to reflect lymphatic overload rather than frank insufficiency. However, significant heterogeneity in study methodologies precluded a quantitative meta-analysis. Future research should focus on establishing standardized, consensus-based imaging protocols to better define the role of lymphoscintigraphy in the diagnosis and staging of lipedema.

Lipedema is a chronic progressive disease characterized by disproportionate and symmetric adipose tissue accumulation, predominantly affecting women, with upper extremity involvement (Type IV) in approximately 30% of cases. This study aimed to evaluate ultrasound measurements of subcutaneous tissue thickness in the upper extremities of women with lipedema compared with matched controls and to establish diagnostic cutoff values for this region.MethodsCross-sectional case-control study including 102 women (51 with clinically diagnosed lipedema and 51 age- and BMI-matched controls). Bilateral ultrasound measurements were obtained at six standardized anatomical points on the upper extremities, and subcutaneous thickness was measured from the dermal-epidermal junction to the deep fascia. Receiver Operating Characteristic (ROC) curves were used to derive diagnostic cutoff values.ResultsSubcutaneous thickness was significantly greater in the lipedema group at all sites, independent of BMI (p < .05). The mid-arm region (10 cm distal to the axillary line) showed the best diagnostic performance (AUC 0.74; sensitivity 82.4%; specificity 51.9%; cutoff >11.4 mm), and four of the six points demonstrated good accuracy (AUC 0.73-0.74).ConclusionUltrasound using standardized anatomical points and defined cutoff values provides good discriminatory capacity for diagnosing upper extremity lipedema and represents an accessible and reproducible adjunct to clinical assessment.

A progressive disease, lipedema is characterized by bilaterally symmetrical and disproportional accumulation of subcutaneous adipose tissue (SAT) in the extremities, leading to severe pain, inflammation, and mobility issues. Lipedema predominantly affects women in all stages of life and treatment options are currently limited as patients' conditions can only be improved to a limited extent by diet or exercise. The pathogenesis of lipedema remains poorly understood and a reliable diagnostic marker is currently missing. Disease progression is marked by stage-dependent morphological adipose tissue changes, such as adipocyte hypertrophy and stage-dependent fibrosis, accompanied by an elevated proportion of anti-inflammatory macrophages. The molecular mechanisms regulating these compositional and structural changes in adipose tissue, and to what extent this altered response is cause or consequence of the disease, remain unclear. Therefore, the analysis of disease-related changes, with a focus on the cellular dynamics and tissue composition changes may help to distinguish lipedema more reliably from adiposity-related comorbidities.

We read with great interest the article on Tranexamic acid use in Liposuction for Lipedema by Bruno and Foti [1]. Evaluating how tranexamic acid affected surgical results and expected blood loss in patients undergoing liposuction for lipedema. The authors provide valuable insights into incidence, prevalence, survival, and diagnostic timelines. However, several methodological considerations merit further discussion. These shortcomings do not undermine the study, but they do suggest the stated treatment effect magnitude may be underestimated. Prospective designs, statistical adjustment for clustering, blinded outcome evaluation, and objective blood loss quantification would all be helpful for future research.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Introduction: Lipedema is a chronic adipose tissue disorder characterized by disproportionate accumulation of subcutaneous fat, primarily affecting the lower extremities. The condition occurs almost exclusively in women and is associated with pain, tissue sensitivity, easy bruising, and progressive functional limitations. These symptoms can impair mobility and negatively affect quality of life.

ObjectivesThe aim of this study was to compare metabolic status and biochemical indices associated with cardiovascular risk, including the triglyceride-glucose (TyG) index, triglyceride-glucose-body mass index (TyG-BMI), and atherogenic lipid indices, between obese individuals with and without lipedema, and to evaluate the potential effect of lipedema on these parameters.Materials and MethodsThis cross-sectional study included 70 obese patients diagnosed with lipedema and 70 obese control individuals without lipedema. Fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride levels were recorded. Based on these parameters, the TyG index, TyG-BMI, atherogenic index of plasma (AIP), atherogenic coefficient (AC), and Castelli risk indices I (CRI-I) and II (CRI-II) were calculated.ResultsNo significant differences were observed between the lipedema and control groups in fasting glucose, total cholesterol, HDL-cholesterol, triglyceride levels, TyG, TyG-BMI, or atherogenic lipid indices (all p > .05). LDL-cholesterol levels were significantly lower in the lipedema group compared with the control group (p = .008). In the lipedema group, TyG-BMI showed a positive correlation with age and BMI, whereas no significant associations were found with symptom duration or pain severity.ConclusionAlthough LDL-cholesterol levels were lower in obese individuals with lipedema, this difference was not reflected in biochemical indices associated with metabolic status and cardiovascular risk. Importantly, metabolic parameters in patients with lipedema accompanied by obesity were comparable to those observed in individuals with obesity alone, suggesting that obesity rather than lipedema may be a more important determinant of metabolic risk in this population. Therefore, metabolic evaluation should not be overlooked in patients with lipedema, and the management of obesity should be considered in treatment planning.

INTRODUCTION: Recent research suggests that body contouring surgeries may reduce benzodiazepine (BNZ) use in patients with anxiety or depressive disorders. This study explores whether similar benefits occur in women with lipedema-a chronic adipose disorder causing pain, limited mobility, and psychological distress-who are often prescribed BNZ. MATERIALS AND METHODS: We conducted a retrospective observational study on 100 adult female patients with Stage I-III lipedema undergoing tumescent or water-assisted liposuction between 2019 and 2024. All participants were on stable BNZ therapy for at least six months before surgery. The primary outcome was BNZ usage at six months postoperatively. Secondary outcomes included anxiety (GAD-7), pain (VAS), sleep quality (PSQI), and body image (BODY-Q) and assessed pre- and post-surgery using validated instruments. DISCUSSION: At six months, 77% of patients reduced or discontinued BNZ (32% stopped entirely), with average daily dosage decreasing from 3.2 ± 1.1 to 1.4 ± 1.2 mg (p < 0.001). Statistically significant improvements were also observed in anxiety, pain, sleep quality, and body image (all p < 0.001). Reductions in BNZ use correlated with improvements in pain (r = 0.56), anxiety (r = 0.47), and body image (r = - 0.52). Only minor complications occurred (8%), and no major adverse events were reported. CONCLUSION: Liposuction for lipedema not only improves physical symptoms but also supports psychological recovery, reducing dependence on benzodiazepines. These findings highlight the potential of surgical treatment as part of an integrated approach to managing chronic conditions with both somatic and mental health components. Further research is needed to confirm long-term effects and underlying mechanisms. LEVEL OF EVIDENCE I: Level I, therapeutic study using a properly randomized controlled trial. 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 .

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.