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Validation and reliability of the Turkish version of the lipedema screening questionnaire - Turkish Journal of Physical Medicine and Rehabilitation

Lipedema is a chronic disorder characterized by the abnormal and disproportionate accumulation of painful subcutaneous adipose fat, primarily affecting the lower limbs and occurring almost exclusively in women. The aim of this controlled cross-sectional study was to compare body image, psychological distress, and psychological well-being in women with (n = 77) and without lipedema (n = 32). Psychological functioning was assessed using validated measures of depressive symptoms (PHQ-9), eating attitudes (EAT-26), perceived stress (PSS), medically unexplained symptoms (M.U.S.), psychological well-being (WHO-5), life satisfaction (SWLS), psychological flexibility (AAQ-II), pain intensity (VAS), together with measures of body image, lifetime psychological burden, maladaptive cognitive beliefs, symptom severity, and anthropometric parameters. Compared with controls, women with lipedema reported significantly greater body image dissatisfaction, perceived distress, M.U.S., depressive symptoms, disordered eating attitudes, and pain, together with lower psychological well-being, life satisfaction, and psychological flexibility (all p < 0.001). Within the lipedema group, PHQ-9 scores were significantly predicted by M.U.S. scores, maladaptive cognitions, and pain intensity (VAS), whereas EAT-26 scores were predicted by PHQ-9 scores and maladaptive cognitions. These findings indicate that lipedema is associated with a substantial psychological burden and support integrating psychological assessment and intervention into multidisciplinary care.

Background: Lipedema is a chronic disorder of subcutaneous adipose tissue characterized by symmetrical fat accumulation in the extremities, pain, and orthostatic edema. Objectives: This study aimed to assess whether high-resolution cutaneous ultrasound can detect measurable tissue-level changes in subcutaneous tissue over six months. Methods: A retrospective, single-center, real-world longitudinal observational cohort study was conducted in 60 women with lipedema followed at three timepoints (baseline, 3 months, 6 months). High-resolution ultrasound (18–20 MHz) measured subcutaneous and dermal thickness at standardized anatomical sites. Results: All primary ultrasound parameters decreased significantly over six months of conservative multicomponent management, which included individualized nutritional counseling and physical activity. Medial proximal thigh subcutaneous thickness declined by 18.7% (48.2 to 39.2 mm; p < 0.001). Edema prevalence fell from 100% to 55.0%. Echogenicity improved significantly between 3 and 6 months, suggesting a delayed structural remodelling effect distinct from early volumetric reduction. Ultrasound reductions were inversely correlated with weight loss, suggesting that ultrasound captures tissue-level information not fully reflected by anthropometric measures alone. Conclusions: Standardized cutaneous high-resolution ultrasound detected consistent tissue-level modifications over six months of routine clinical follow-up, capturing changes beyond anthropometric measures and representing a candidate monitoring tool warranting evaluation in controlled study designs.

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.

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.

ObjectivesGenerative artificial intelligence (AI) models capable of producing photorealistic medical images are increasingly proposed for patient education, clinical illustration, and trainee instruction. However, their ability to accurately represent anatomically distinct disease subtypes remains unclear. This study evaluated the diagnostic accuracy of a widely used generative AI model in producing images corresponding to the five anatomical lipedema types defined by the Schmeller classification.MethodsIn this prospective audit, ChatGPT’s image-generation interface was prompted to create 60 images for each lipedema type (Types I–V),yielding 300 images. Prompts were standardized and limited to the subtype label without additional descriptors. Two clinicians independently classified each image into one of the five lipedema types or as indeterminate, blinded to the original prompt; disagreements were resolved by a third clinician. Diagnostic performance was assessed using a confusion matrix and per-type sensitivity, specificity, positive predictive value(PPV), negative predictive value (NPV),F1-score,and one-vs-rest receiver operating characteristic area under the curve (ROC AUC). Overall accuracy and Cohen’s κ statistics were also calculated.ResultsAll 300 images were evaluable. The model generated anatomically consistent images for Types I,II, and III (sensitivity = 1.00 for each). Specificity was 1.00 for Types I and II but 0.50 for Type III because all images requested as Types IV and V were classified as Type III. Consequently, the model failed to generate any images consistent with Type IV(arm-predominant) or Type V(calf-isolated) lipedema (sensitivity = 0.00 for both). Overall accuracy was 0.600. Unweighted and quadratic-weighted Cohen’s κ values were 0.500 and 0.667, respectively. Micro- and macro-averaged ROC AUC were both 0.750.ConclusionThe model reproduces severity gradients within lower-extremity lipedema but systematically collapses anatomically distinct subtypes into the dominant Type III phenotype, failing to depict arm-predominant and calf-isolated disease. Current generative AI systems may therefore encode lipedema as a single visual phenotype rather than a distributed anatomical entity, limiting their reliability for medical education and clinical communication.

Background Lipedema is a painful subcutaneous adipose tissue (SAT) disorder that mainly affects women. Patients present fat accumulation in the limbs, especially in the legs. Methods A pilot-controlled clinical trial was conducted on a sample of 18 patients with lipedema, equally divided into a control group (CG) and an experimental group (EG). Both groups were given 10 sessions of diathermy on the inner side of their knees, 10 min of treatment per knee. EG was given the diathermy dose at high-intensity heat, while CG was given sham treatment. Measurement instruments used were circumferential measurements, ultrasound measurements, algometry, VAS, and SF-12 questionnaire. Data were collected at baseline, at the end of the study and 5 weeks later. Results significant reductions in left knee circumference were observed in the EG compared with the CG (p = 0.004 post-intervention and p = 0.017 at follow-up). No significant differences were found in ultrasound, algometry, or VAS measurements within or between groups. Conclusions High-intensity heat diathermy resulted in a reduction in knee circumference, suggesting a potential effect on limb volume.

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.