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ObjectivesThis study aimed to analyze the complex components of pain in lipedema and to evaluate correlations among key pain-related parameters, including intensity, hypersensitivity, catastrophizing, central sensitization, and neuropathic pain.MethodsThis prospective study was conducted between June 2025 and September 2025. Patients aged 18 or older with a diagnosis of lipedema were included. Demographic/clinical characteristics were recorded. Pain intensity, hypersensitivity, pain catastrophizing, central sensitization, and neuropathic pain were assessed using the Numeric Rating Scale (NRS), a 0-3 verbal rating scale, the Pain Catastrophizing Scale, the Central Sensitization Inventory, and the painDETECT questionnaire, respectively.ResultsA total of 85 patients were included in the study. Patients had a median age of 44 years, a median Body Mass Index of 29.24 kg/m2, and most were classified as stage 2 lipedema (50.6%). Pain intensity was moderate, with a median NRS score of 5, while hypersensitivity levels were moderate (41.2%) to high (34.1%) in most patients. Pain catastrophizing, central sensitization, and neuropathic pain were present in 35.1%, 83.5%, and 27.1% of the patients, respectively. Pain intensity was significantly positively correlated with hypersensitivity, pain catastrophizing, central sensitization, and neuropathic pain (p < 0.05). All parameters were significantly correlated with each other (p < 0.05).ConclusionCentral sensitization may be observed in patients with lipedema and is associated with other pain parameters. The findings highlight significant interrelationships among pain intensity, hypersensitivity, pain catastrophizing, and central sensitization. Pain needs to be assessed in detail in patients with lipedema.

Lipoedema is a chronic adipose tissue disorder mainly affecting women with excess subcutaneous fat deposition on the lower limbs, associated with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is not well studied. We conducted a genome-wide association study (GWAS) for this disorder in a clinically ascertained cohort from Spain and performed a meta-analysis with the UK lipoedema cohort GWAS. We then used the results of this study as a replication of the inferred UK Biobank “lipoedema phenotype” study. Whilst our meta-analysis alone did not identify any genome-wide significant associations, our clinical cohorts provide support for three loci identified through the UKBB study: the chr2q24.3 GRB14-COBLL1 locus (rs6753142, PMETA=1.64x10-6), chr6p21.1 VEGFA locus (rs4711750, PMETA=8.99x10-7) and the chr5q11.2 ANKRD55-MAP3K1 locus (rs3936510, PMETA=1.67x10-5). We identify numerous rare SNPs with strong association signals in our meta-analysis (P<1x10-6) with support in both UK and Spanish datasets, three of which also show nominal support in the UKBB (P<0.05). These findings provide a starting point towards understanding the genetic basis of clinical lipoedema and demonstrate the utility of the interplay of large-scale biobanks genetic data and clinically ascertained cohorts to elucidate the genetic architecture of lipoedema.

Background: Lipedema is a chronic adipose tissue disorder predominantly affecting women and is frequently misclassified as obesity. While its physical manifestations are increasingly recognized, less attention has been paid to eating attitudes and psychological well-being in this population. The objective of this study was to descriptively explore eating attitudes and psychological well-being in women with lipedema.Methods:This exploratory cross-sectional study used an anonymous online survey to describe eating attitudes and psychological well-being in women with lipedema. A total of 47 participants completed the Eating Attitudes Test (EAT-26) and the World Health Organization-5 Well-Being Index (WHO-5). Descriptive statistics were used to summarize screening indicators of disordered eating risk and reduced psychological well-being.Results:Approximately two-thirds of participants scored at or above the EAT-26 screening cut-off, reflecting elevated screening indicators of disordered eating risk. When behavioral risk indicators were included, over 70% screened positive according to EAT-26 criteria. Reduced psychological well-being (as indicated by a WHO-5 score of ≤50) was observed in about one-fifth of the sample.Conclusion:In this exploratory sample of women with lipedema, elevated screening indicators of disordered eating risk and reduced psychological well-being were commonly observed. These findings offer preliminary insights suggesting that eating-related risk and reduced well-being may be prevalent in this population. Further research using larger, clinically verified samples is needed to better understand the psychological aspects of lipedema.

Background: Lymphedema is a debilitating condition with high morbidity, yet despite advances in management, diagnostic ambiguity and fragmented referr...

BACKGROUND: Postoperative fibrosis is a frequent complication following liposuction for lipedema. Serrapeptase, a proteolytic enzyme with purported anti-inflammatory and antifibrotic effects, is used empirically, but robust evidence supporting its efficacy is lacking. This study aimed to assess the clinical effectiveness of postoperative serrapeptase supplementation in reducing fibrosis following lower limb liposuction for lipedema. METHODS: This retrospective, observational cohort study included 50 female patients with a confirmed diagnosis of lipedema undergoing tumescent liposuction. Patients were allocated to either a serrapeptase group (n = 25), receiving 60,000 IU daily for 4 weeks, or a control group (n = 25) receiving standard care alone. The primary outcome was tissue stiffness measured by quantitative ultrasound elastography (QUS). Secondary outcomes included B-mode ultrasonography, patient-reported pain (VAS), and clinical assessment of induration. Evaluations were performed at baseline, 4 weeks, and 3 months. RESULTS: Baseline characteristics were comparable between groups. No statistically significant differences were observed in the primary outcome of tissue stiffness at 4 weeks (14.8 ± 3.1 kPa vs. 15.2 ± 3.0 kPa; p = 0.62) or 3 months (13.7 ± 2.9 kPa vs. 14.0 ± 3.2 kPa; p = 0.78). Similarly, no significant benefits were seen in secondary outcomes, including fibrotic changes on ultrasound, VAS pain scores, or clinical induration (p > 0.05 for all). Serrapeptase was well-tolerated with no adverse events reported. CONCLUSIONS: Oral serrapeptase supplementation did not demonstrate measurable efficacy in preventing postoperative fibrosis or improving patient-reported outcomes following liposuction for lipedema. These findings do not support its routine use in this clinical setting. 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 .

ObjectiveTo evaluate the educational quality, reliability, and transparency of YouTube™ videos on lipoedema, and to examine associations with uploader type and engagement metrics.MethodsOn 15 May 2025 we searched YouTube™ for "lipoedema," screened the first 200 relevance-ranked items, and included videos ≥60 s with intelligible audio. Advertisements, duplicates and soundless videos were excluded. Two independent physicians in Physical Medicine and Rehabilitation (PM&R) rated eligible videos using DISCERN, the Global Quality Score (GQS), and the Journal of the American Medical Association (JAMA) benchmark criteria; disagreements were discussed and original ratings retained for agreement analyses. We recorded upload date, duration, views, likes, comments, channel subscribers, uploader category, and content domain.ResultsWe analyzed 92 YouTube™ lipoedema videos uploaded between 25 February 2015 and 8 January 2025. Uploader mix: vascular surgeons 39.1% (largest) and PM&R physicians 4.3% (smallest); the most common topic was definition + symptoms + management (26.1%). Mean DISCERN totals were 33.47 ± 9.88 and 33.42 ± 8.68 (both poor); mean GQS 2.18 ± 0.82 and 2.43 ± 0.81; only 6.6% were high quality and none scored 5/5. Views correlated strongly with likes and comments (both p < .001), moderately with duration (p < .01), and weakly with subscribers (p < .05). Inter-rater agreement was strong (r = 0.859/0.663/1.000; all p < .001).ConclusionThe overall quality and transparency of YouTube™ lipoedema videos are suboptimal despite substantial engagement. Increasing expert-authored, evidence-based content-particularly from PM&R- and co-produced patient-clinician videos may better align reliability with reach.

Lipoedema is a chronic disorder primarily affecting women. Often mistaken for obesity due to its characteristic build-up of fat cells in the legs and sometimes arms, lipoedema leaves women vulnerable to social stigma. This study investigated the role of fears of compassion and depressive symptoms in the context of weight stigma and internal weight bias in women with lipoedema.

Background Lipedema is characterized by disproportionate gluteofemoral adiposity with anti-inflammatory properties. We hypothesized that this phenotype may confer immunological protection against T-helper 1 (Th1)-mediated autoimmunity ("Immunological Shield Hypothesis"). Objective The objective of this study is to explore whether women with a dual-energy X-ray absorptiometry (DXA)-defined lipedema-like phenotype, characterized by disproportionate gluteofemoral fat accumulation, exhibit distinct immunometabolic profiles and lower prevalence of celiac disease (CD) autoimmunity in a nationally representative sample. Methods The cross-sectional analysis included 3,833 women from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Celiac disease (n=11, 0.56% weighted prevalence) was defined by strict serology (tissue transglutaminase {tTG}-IgA+/endomysial antibody {EMA}-IgA+); lipedema phenotype was defined as leg-to-trunk fat ratio of >90th percentile via DXA. Results Women with celiac disease exhibited 7.4% lower gynoid fat (39.5% versus 42.6%, p=0.0007), persisting in overweight/obese strata. Conversely, the lipedema phenotype demonstrated superior metabolic health: 44.2% lower homeostatic model assessment of insulin resistance (HOMA-IR) (p<0.001) and 7.6% lower neutrophil-to-lymphocyte ratio (NLR) (p=0.012). Conclusions This exploratory population-based analysis identifies phenotypic divergence in fat distribution between the DXA-defined lipedema phenotype and celiac disease autoimmunity, yielding observations consistent with, but not confirmatory of, the "Immunological Shield Hypothesis." While limited by the small number of celiac cases (n=11), a sample size insufficient to detect prevalence differences for a ~7%-9% phenotype, for which approximately 225-600 celiac cases would be required, the observed differences in gynoid adiposity (7.4% reduction, p=0.0007) and the favorable metabolic profile of the lipedema phenotype (44.2% lower HOMA-IR and 7.6% lower NLR) suggest biological plausibility warranting validation in larger, targeted cohorts. These findings motivate targeted studies to evaluate whether dietary exposures, including gluten-related immune activation, interact with gluteofemoral adipose biology in lipedema.

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Lipoedema is a chronic, progressive condition characterised by disproportionate fat accumulation in the lower extremities, often misdiagnosed due to symptom overlap with obesity. Weight management is a key component of lipoedema treatment, yet the role of bariatric surgery remains unclear. This systematic review evaluates the impact of bariatric and metabolic surgery (BMS) on lipoedema symptoms, weight loss outcomes, and the need for further interventions. A systematic search of PubMed, Scopus and the Cochrane Library was conducted up to January 2025 following PRISMA guidelines. Studies reporting on patients with lipoedema (or equivalent diagnoses) who underwent BMS were included. Quality was assessed using the Joanna Briggs Institute (JBI) checklist for case reports and the National Heart, Lung and Blood Institute (NHLBI) tool for case series. Seven studies met the inclusion criteria (five case reports, two cohort studies), comprising 51 patients. All underwent BMS, primarily sleeve gastrectomy or Roux-en-Y gastric bypass. One study (n = 31) reported a significant reduction in thigh volume and weight loss comparable to controls. The remaining studies found persistent or worsened lower body disproportionality and no improvement in pain. Postoperative lipoedema diagnoses were common, raising concerns over diagnostic accuracy. Overall weight loss averaged 33.9% total weight loss. Bariatric and metabolic surgery achieves meaningful weight reduction in patients with lipoedema and obesity but does not consistently improve core lipoedema symptoms. Its role remains adjunctive rather than primary. Preoperative identification and documentation of lipoedema features are recommended, with a postoperative plan for adjunct conservative therapies and selective consideration of lymph-sparing liposuction where symptoms persist. Larger prospective studies using standardised definitions and outcome measures are needed to clarify its therapeutic value in this population.

BACKGROUND: lipedema is a chronic, progressive adipose disorder predominantly affecting women, characterized by painful, symmetrical subcutaneous fat accumulation, and typically resistant to lifestyle interventions. The pathophysiology of advanced-stage lipedema remains poorly defined, and no validated biomarkers or targeted therapies are currently available. METHODS: in this observational study, we applied a comprehensive multi-omics approach to dissect the molecular and metabolic alterations underlying late-stage lipedema. RESULTS: Genome-wide DNA methylation profiling identified over 5,000 differentially methylated CpG sites affecting genes involved in receptor tyrosine kinase signaling, phospho-metabolism, and immune pathways. Transcriptomic analysis revealed profound downregulation of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and fatty acid β-oxidation, alongside disruption of the sirtuin pathway and extracellular matrix remodeling. Integrative analysis pinpointed AKT1 as a central regulatory node: its promoter region was hypomethylated, correlating with increased gene expression and protein phosphorylation. Metabolomic profiling confirmed AKT1-linked metabolic dysregulation, including altered levels of L-arginine, NADP+, ATP, guanosine, glycerol, and glutamate, indicating impaired redox balance and energy metabolism. Trans-omic network analysis positioned AKT1 at the intersection of multiple dysregulated pathways, suggesting its key role in advanced-stage lipedema. CONCLUSIONS: the consistent enhancing of AKT pathway signaling across omic layers highlights its potential not only as a biomarker for disease stratification but also as a putative druggable target for therapeutic intervention. These findings offer new mechanistic insights into lipedema pathophysiology and provide a rationale for future personalized treatment strategies guided by AKT1-centric molecular profiling.

PURPOSE: Lipedema is a chronic disorder that affects the subcutaneous adipose tissue of the lower and upper limbs and results in painful fat accumulations. During the reproductive life span, about 11% of women are affected; however, there are a high number of suspected undiagnosed and thus untreated cases. METHODS: The aim of this systematic review was to evaluate the association between hormones and the pathophysiological mechanisms of lipedema development. Inclusion criteria were: lipedema, lipoedema, estrogen, estrogen antagonists, female sex hormones, hormones, insulin, puberty, pregnancy, menopause, subcutaneous fat tissue, and subcutaneous adipose connective tissue. RESULTS: The literature search yielded 121 hits; after deduplication, 64 records were screened. After abstract and full-text screening 15 publications were suitable for being included in the systematic review. Overall, four different pathophysiological hypotheses were postulated: (1) general hormonal imbalance, (2) changes in growth hormone balance, (3) metabolic imbalance such as changes in adipose stem cells in relation to adipokines or leptin in association with the transcription factor PPARγ, and (4) changes in estrogen metabolism as well as alterations in the function of estrogen receptors. CONCLUSION: Lipedema appears to be a multifactorial condition primarily driven by hormonal dysregulation-especially involving estrogen-alongside metabolic and possible genetic components. The findings support the reclassification of lipedema as a hormonally influenced disorder distinct from obesity, emphasizing the need for further research into diagnostic biomarkers, targeted therapies, and the role of genetic susceptibility.

BackgroundEndothermal ablation (ETA) is a well-established treatment for chronic venous insufficiency (CVI). However, its effectiveness in patients with concomitant lipedema remains poorly described. Given the distinct pathophysiological features and symptom burden of lipedema, outcomes may differ in this subgroup.MethodsWe conducted a prospective cohort study of patients with CVI alone and those with CVI plus lipedema. All patients underwent ETA, with adjunctive phlebectomies as indicated. Quality of life (QoL) was assessed using the EQ-5D-VAS and CIVIQ-20 questionnaires before surgery and at 3 months postoperatively. Demographic and clinical variables included age, body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), and symptom profile. The primary outcome was the change in CIVIQ-20 score at 3 months. Secondary outcomes included changes in EQ-5D-VAS and postoperative complications (hematoma, paresthesia, superficial and deep vein thrombosis).ResultsA total of 48 patients were included (32 with CVI alone, 16 with CVI and lipedema). Preoperative QoL impairment was significantly greater in the lipedema cohort (median CIVIQ-20: 61.0 [49.5-69.5]) compared with CVI alone (46.0 [33.0-56.0], p = .001). At 3 months, both groups demonstrated significant improvement (p < .001 for within-group change). However, the magnitude of improvement was greater in CVI alone (median reduction: -13.5 [-19.5 to -5.0]) than in CVI plus lipedema (-4.0 [-7.0 to -1.5]; p = .012). Multivariable regression identified higher baseline CIVIQ-20 (β = 0.60; SE = 0.09; p < .001) and lipedema status (β = 12.44; SE = 2.43; p < .001) as independent predictors of poorer postoperative CIVIQ-20 outcomes. Paresthesia was more frequent in lipedema patients (25.0% vs 18.8% at 1 month; 12.5% vs 6.2% at 3 months).ConclusionWhile ETA significantly improves QoL in patients with CVI, those with concomitant lipedema experience smaller gains and a higher rate of postoperative paresthesia. These findings highlight the importance of setting realistic expectations and counseling lipedema patients regarding potential outcomes of venous interventions.

Lipedema is a chronic disease characterized by the symmetrical accumulation of adipose tissue in the lower body, primarily affecting women. Despite being recognized for over 85 years, the pathophysiology, diagnosis, and treatment of lipedema remain complex and not fully understood. This review consolidates current knowledge, emphasizing histological, genetic, and hormonal factors, alongside diagnostic and therapeutic approaches. Histological studies highlight changes such as adipocyte hypertrophy, increased fibrosis, and vascular alterations like angiogenesis. Genetic studies suggest a strong familial component, with multiple loci potentially influencing disease onset, yet the condition remains polygenic and influenced by environmental factors. Hormonal influences, particularly estrogen, play a significant role in disease pathogenesis. Diagnostic imaging techniques like dual-energy X-ray absorptiometry (DXA), ultrasound (US), and magnetic resonance imaging (MRI) provide valuable insights but are not definitive. Therapeutic strategies, including diet, weight loss, and Complex Decongestive Therapy, offer symptom management but are not curative, with liposuction considered for severe cases where conservative methods fail. The condition's complexity stems from genetic, hormonal, and environmental influences, necessitating further research to improve diagnostic and treatment strategies. Integrating genetic and hormonal insights into clinical practice could enhance patient outcomes and quality of life, highlighting the need for continued exploration and understanding of lipedema.