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Lipedema is a chronic and progressive disorder characterized by disproportionate fat accumulation, mainly affecting the lower extremities of women, and commonly accompanied by sensations of heaviness, tenderness, and discomfort. While its pathogenesis remains largely unknown, genetic, hormonal, and microvascular factors have been implicated. The condition often coexists with psychological distress, which significantly detracts from the quality of life of affected individuals. Diagnosis is primarily clinical, as no specific biomarkers or imaging modalities have been proven sufficiently reliable for identification. Proposed managements are controversial, although current treatment focuses on symptom management and disease control through conservative methods such as compression and non-invasive device therapies, specialized diets, and physical rehabilitation or surgical treatments. Psychological support is vital in addressing the emotional challenges of the condition. Despite recent advancements in the understanding and management of lipedema, there remains a critical need for further research to establish standardized diagnostic criteria and targeted therapeutic strategies for this debilitating condition.

Lipedema is a chronic, underdiagnosed adipose disorder marked by disproportionate fat accumulation, pain, and impaired mobility. Misdiagnosis as obesity or lymphedema delays care and increases morbidity. We systematically reviewed clinical features, diagnostic criteria, and management options (conservative and surgical). A comprehensive search of the PubMed database was conducted in January 2025 for English-language articles published from January 1950 to January 2023 using the keywords "lipedema" or "lipoedema." Additional references were identified via manual review of relevant systematic reviews. Two independent reviewers screened studies and graded quality using a modified Oxford scale. Of 339 articles, 61 met the inclusion criteria. Most were observational cohorts, case series, or expert consensus, with few randomized trials. Conservative therapies, including ketogenic or Rare Adipose Disorders (RAD) diets, compression therapy, and aquatic exercise, were associated with reduced pain and swelling (Grade 2A-2B). Tumescent liposuction showed the strongest evidence for sustained symptom improvement, mobility, and quality of life (Grade 1 recommendation, evidence quality 2-3). Lipedema is a distinct, progressive condition requiring early recognition and intervention. Conservative therapies may provide partial relief, but tumescent liposuction remains the most effective treatment. Standardized diagnostic criteria, validated patient-reported outcomes, and clearer guidelines are needed to harmonize care and improve long-term outcomes.

Background: Emerging evidence suggests that lipedema may share hormonal, inflammatory, and genetic mechanisms with gynecologic diseases, particularly endometriosis. However, the extent and nature of these interrelationships remain poorly characterized, supporting the need for this scoping review. Objectives: To map and synthesize the available evidence on the clinical, pathophysiological, and epidemiological interrelationships between lipedema in women, endometriosis, and other gynecologic diseases. Methods: Searches were conducted in international and regional health databases, including MEDLINE (PubMed), CINAHL, Scopus, Embase, Web of Science, the Cochrane Library, LILACS/VHL, APA PsycInfo, SciELO, Epistemonikos, and La Referencia, as well as grey literature sources and relevant institutional websites. There were no language restrictions. The search period began in 1940, the year in which lipedema was first described by Allen and Hines. Study selection followed a two-stage process conducted independently by two reviewers, consisting of title and abstract screening followed by full-text review. Data extraction was performed using a pre-developed and peer-reviewed instrument covering participants, concept, context, study methods, and main findings. The review protocol was registered in the Open Science Framework. Results: Twenty-five studies from ten countries were included. Synthesized evidence supports the characterization of lipedema as a systemic condition with metabolic and hormonal dimensions. Key findings include symptom onset linked to reproductive milestones, a high frequency of gynecologic and endocrine comorbidities, and molecular features overlapping with steroid-dependent pathologies. These patterns reflect a recent shift from a predominantly lymphovascular paradigm toward a more integrated endocrinometabolic framework. Conclusions: The findings indicate that lipedema clusters with hormone-sensitive gynecologic and endocrine features across reproductive life stages.

Background. Lipedema is a chronic and progressive fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose tissue predominantly in the lower body. Symptoms include pain, bruising, swelling, and subcutaneous nodules that are resistant to traditional interventions such as diet and exercise. Aim. The objective of this review is to summarize recent evidence on the characteristics, pathophysiology, diagnosis and treatment of lipedema. Matherial and Methods. A literature search was conducted using the PubMed database. The inclusion criteria were “full free text” and English scientific articles, published between 2015 and 2025. A total of 74 records were found, of which    publications were ultimately included in the review. Results. Awareness of lipedema in the medical field is increasing, but its differential diagnosis still remains a challenge. Lipedema is often unrecognized or misdiagnosed as obesity or lymphedema. Conclusion. This narrative review provides a deeper understanding of lipedema as a serious condition, discusses its pathophysiology and treatment options. The data reveal advances in knowledge, particularly in conservative and surgical treatment with a focus on improving quality of life. However, there is a lack of scientific evidence confirming the safety and efficacy of various treatment methods. Further research is required to ensure the safety and increase the efficacy of treatment for this complex condition known as lipedema.

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Lipedema is a chronic inflammatory disorder of adipose tissue that predominantly affects women and is characterized by disproportionate subcutaneous fat accumulation, pain, spontaneous bruising, and significantly impaired quality of life. Although hormonal influences on its pathophysiology have been increasingly recognized, evidence-based treatment options remain limited. Recently, gestrinone has been proposed as an off-label therapy based on hormonal mechanistic hypotheses. A critical narrative review of the literature was conducted using international databases to identify clinical or pharmacological evidence supporting its use in lipedema. No clinical trials, observational studies, case series, or case reports directly evaluating this therapy were identified. Existing proposals rely exclusively on theoretical extrapolations lacking clinical validation. Therefore, current evidence does not support the use of gestrinone in the treatment of lipedema, and its use should be considered experimental until adequately designed clinical studies are available.Keywords: lipedema; adipose tissue; hormone therapy; gestrinone; evidence-based medicine

Lipedema is a chronic, female-predominant disorder of subcutaneous adipose tissue characterized by disproportionate fat expansion, pain, and fibrosis. Despite its high prevalence, the cellular mechanisms underlying lipedema remain poorly understood. While the clinical features have been extensively described, its biology of adipose tissue dysfunction and aberrant intercellular communication is still unclear. In comparison to obesity, lipedema is marked by local dysregulation of adipocyte-stromal and adipocyte-vascular interactions. In this hypothesis perspective, we discuss emerging mechanistic concepts from a cell biology perspective that are particularly relevant to lipedema, focusing on (i) organelle contact site dynamics in adipocytes and their role in lipid handling and stress adaptation; (ii) extracellular vesicle (EV)-mediated crosstalk between endothelial cells, adipocytes, and immune cells as a driver of localized inflammation and fibrosis; and (iii) estrogen-linked signaling pathways that may imprint EV cargo and cellular behavior in a sex-specific manner. By integrating these perspectives, we highlight open experimental settings and mechanistic parallels to other adipose tissue pathologies that help understanding lipedema as a distinct cellular and molecular entity. Investigating how organelle biology, extracellular vesicles communication and hormonal context intersect in adipose tissue may uncover novel biomarkers and therapeutic entry points for this long-neglected condition.

Lipedema is a chronic adipose tissue disorder characterised by disproportionate accumulation of subcutaneous fat within specific anatomical depots, most commonly the lower extremities, with relative sparing of the trunk. Despite increasing clinical recognition, the mechanisms underlying the selective vulnerability of particular adipose depots and the progressive tissue remodelling observed in lipedema remain poorly understood. Emerging evidence suggests that lipedema is associated with complex alterations in adipocyte biology, adipose stem and progenitor cell (ASPC) function, immune signalling, vascular integrity, extracellular matrix remodelling, and lymphatic homeostasis, indicating that the disease extends beyond simple fat accumulation. Recent advances in adipose tissue biology have demonstrated that adipose depots are not functionally uniform structures, but rather anatomically distinct cellular ecosystems with unique developmental origins, transcriptional programs, stromal composition, immune niches, and metabolic properties. These depot-specific characteristics may provide an important framework for understanding the regional distribution and progression of lipedema. However, while substantial progress has been made in defining differences between visceral and subcutaneous adipose tissue, heterogeneity between individual subcutaneous depots remains comparatively underexplored despite its likely relevance to disorders of regional adipose expansion. The emergence of single-cell and spatial transcriptomic technologies has transformed the study of adipose tissue by enabling high-resolution mapping of adipocytes, stromal populations, vascular cells, and immune microenvironments within healthy and diseased tissue. These approaches offer an unprecedented opportunity to investigate depot-specific cellular states, intercellular signalling networks, and spatial tissue architecture in lipedema. In this review, we synthesise current evidence regarding tissue remodelling and adipose depot heterogeneity in lipedema and examine how single-cell and spatial omics approaches may advance mechanistic understanding of disease pathophysiology. We further discuss current technical and conceptual limitations within the field and highlight future directions for developing integrated adipose tissue atlases capable of identifying disease-driving cellular programs and therapeutic targets in lipedema.

Introduction  Lipedema is a chronic disease characterized by symmetrical and painful accumulation of subcutaneous fat, influenced by genetic and hormonal factors, and frequently misdiagnosed as obesity or lymphedema. Materials and Methods  In the present narrative review, we searched the PubMed and SciELO databases for articles published between 2015 and 2025, in Portuguese and English, addressing the diagnosis and the clinical or surgical management of lipedema. Results  In the PubMed search, we identified 299 studies, which were reduced to 106 after the removal of duplicates, with a progressive increase in publications since 2020; in the search on SciELO, we only retrieved 7 studies, all of which were also indexed in PubMed. The results reinforce that lipedema presents a complex pathophysiology, involving adipocyte hypertrophy and hyperplasia, chronic inflammation, microvascular dysfunction, and estrogen-related influence. International consensus indicates that diagnosis is essentially clinical, and that conservative treatment should be prioritized, including weight management, nutritional guidance, low-impact exercise, compression therapies, and psychosocial support. Surgical intervention, particularly tumescent or water-assisted liposuction techniques, is reserved for refractory cases and does not constitute a definitive cure. The growing alignment among consensus statements published over the past 5 years highlights the need for standardized diagnostic criteria and therapeutic protocols. Conclusion  The effective management of lipedema requires a multidisciplinary approach, continuous professional education, and strengthening of research that enable the establishment of evidence-based clinical guidelines. Keywordsdiagnosis; lipedema; literature review; surgery; treatment

Lipedema is a chronic and often debilitating adipose tissue disorder that primarily affects women. The disease is characterized by disproportionate and symmetrical accumulation of subcutaneous fat in the extremities. Despite the high prevalence of lipedema, which affects ∼10% of women, and its significant impact on patient quality of life, lipedema is understudied and often misdiagnosed as other disorders (obesity or lymphedema). In this review, we explore the current understanding of lipedema through clinical, tissue, and cellular lenses, and examine suspected pathological mechanisms, including hormonal influences (such as estrogen), adipocyte hypertrophy and hyperplasia, increased extracellular matrix (ECM) fibrosis, and specialized immune cell involvement, including M2 macrophage infiltration. Recent advancements in adipose tissue engineering, including organoids, fat-on-a-chip platforms, and the use of induced pluripotent stem cells (iPSCs) are explored as platforms to study lipedema pathogenesis.

Lipedema is a chronic disorder characterized by abnormal subcutaneous fat accumulation, mainly in women's lower limbs. The aim of the study was to analyze the safety and efficacy of liposuction in treating lipedema. A systematic review was conducted in PubMed, Scopus, and MEDLINE until June 2024 using the terms "lipedema," "liposuction," "results," and "complications." Twenty-five studies were included (n = 2373 patients). Liposuction, mainly using the tumescent infiltration, reduced pain, BMI, and functional limitations, with improvements in mobility and quality of life. Mean aspirated fat volume was 3077 mL per session and 6111 mL per treatment course. Complications were uncommon (hematomas, edema, anemia, DVT, and rare methemoglobinemia). Moreover, improvements were maintained during the follow-up, suggesting that the beneficial results were sustained over time. Although 15 studies reported using tumescent, only 2 fully described the anesthetic fluid composition. Liposuction is a safe and effective treatment for lipedema, but variability in techniques and postoperative care highlights the need for standardized protocols and further research. Level of Evidence: 4 (Therapeutic).

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 lipoedema patients with obesity but does not consistently improve core lipoedema symptoms. Its role remains adjunctive rather than primary. Larger prospective studies using standardised definitions and outcome measures are needed to clarify its therapeutic value in this population.

ObjectivesLipedema is a chronic condition that predominantly affects women, leading to painful, disproportionate fat distribution in the limbs. This systematic review and meta-analysis aimed to characterize health-related quality of life (HRQoL) across multiple domains in individuals with lipedema.MethodsWe systematically reviewed studies from inception to 3 July 2025 in MEDLINE (via PubMed) and Cochrane Controlled Register of Trials (CENTRAL) that primarily assessed HRQoL in individuals with lipedema. Data were extracted from studies using HRQoL assessment scales. The methodological quality of included studies was assessed using an adapted version of the Newcastle-Ottawa Scale for cross-sectional studies. The review protocol was pre-registered with PROSPERO (CRD42024590792). A random-effects meta-analysis was conducted to compute pooled mean HRQoL scores across various domains.ResultsFourteen cross-sectional studies involving nine countries and 3851 participants were included. The meta-analysis found significant impairments in multiple HRQoL domains: physical functioning (61.19, 95% CI: 56.77-65.60), pain (51.77, 95% CI: 45.01-58.53), social functioning (63.24, 95% CI: 58.44-68.04), emotional well-being (64.19, 95% CI: 59.86-68.52), and energy/fatigue (43.50, 95% CI: 39.32-47.68).ConclusionLipedema significantly affects HRQoL, with major deficits in physical, emotional, and social functioning. These findings highlight the need for greater clinical awareness and comprehensive management strategies, including both physical and psychological interventions, to improve the quality of life for individuals with lipedema. Further research is needed to explore long-term effects and optimize treatment approaches.

INTRODUCTION: Lipedema is a chronic inflammatory disease characterized by symmetrical deposition of adipose tissue in the upper and lower limbs, disproportionate to the trunk. It primarily affects women. The objective of this study was to evaluate the effects of surgical treatment in patients with lipedema who are refractory to conservative management. METHODS: We conducted a systematic review and single-arm meta-analysis in accordance with PRISMA guidelines. Retrospective studies involving patients who underwent surgical treatment after failing clinical management were included. Means and proportions were pooled using the inverse variance method and logit transformations, and heterogeneity was assessed using the I2 statistic. RESULTS: We included 6 studies comprising 429 patients, with follow-up ranging from 6 months to 44 months. In this meta-analysis, surgical treatment with tumescent liposuction resulted in significant clinical improvements for patients with lipedema. The pooled mean preoperative pain score was 5.64 (95% CI: 3.67-8.69), which decreased to 1.19 (95% CI: 0.91-4.22) postoperatively. Sensitivity to touch or pressure was reduced from a preoperative mean of 5.77 (95% CI: 4.10-8.10) to 1.96 (95% CI: 1.17-3.29) after surgery. Swelling scores improved from 5.47 (95% CI: 3.73-8.02) preoperatively to 2.14 (95% CI: 1.31-3.48) postoperatively, while restriction of movement scores decreased from 3.76 (95% CI: 2.48-5.72) to 0.77 (95% CI: 0.36-1.64). CONCLUSION: The results of this single-arm meta-analysis, which included six studies and 429 patients with lipedema refractory to clinical treatment and undergoing surgical intervention, demonstrate that tumescent liposuction is associated with reductions in postoperative pain and edema, as well as improvements in cosmetic outcomes, quality of life, and mobility. The duration of follow-up was adequate to capture relevant clinical outcomes and adverse events. However, lipedema remains a condition that requires further high-quality studies to define the optimal therapeutic approach. 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 ."

Background: Lipedema is characterized by disproportionate gluteofemoral adiposity, often regarded as a metabolic sink, yet its relationship with systemic autoimmunity, specifically celiac disease (CD), remains unexplored. Objective: We investigated the immunometabolic profiles and body composition patterns distinguishing lipedema phenotypes from celiac disease autoimmunity. Methods: This cross-sectional analysis included 3,833 women from NHANES 2011–2014. Celiac disease was defined by strict serology (tTG-IgA+ and EMA-IgA+), while the lipedema phenotype was defined as a leg-to-trunk fat ratio >90th percentile via dual-energy X-ray absorptiometry (DXA). We assessed gynoid fat mass, HOMA-IR, and neutrophil-to-lymphocyte ratio (NLR) compared to controls. Results: CD prevalence was 0.56% (n=11). Women with CD exhibited significantly lower gynoid region percent fat compared to non-celiacs (39.5% vs. 42.6%, p=0.0007). Conversely, the lipedema phenotype was associated with a distinct anti-inflammatory and insulin-sensitive profile, characterized by 44.2% lower HOMA-IR (p<0.001) and 7.6% lower NLR (p=0.012) compared to controls. While broad lipedema criteria did not reach statistical significance for CD exclusion due to low case numbers (p=0.570), no celiac cases were observed in the highest tier of gynoid adiposity. Conclusions: Although prevalence differences did not reach statistical significance, this study of US women demonstrates a phenotypic divergence where celiac disease is associated with reduced gynoid adiposity, contrasting with the superior immunometabolic profile observed in the lipedema phenotype. These findings suggest that these conditions represent opposing physiological states regarding gynoid adipose tissue function.

Lipedema, a chronic condition primarily affecting women, is characterized by abnormal subcutaneous fat accumulation and swelling in the extremities (while sparing the hands, feet, and trunk). This disease is associated with genetic predisposition, hormonal imbalances, impaired lymphatic function, and vascular dysfunction. Lipedema does not directly cause weight gain, but excess weight can worsen symptoms and accelerate disease progression. Bariatric surgery is considered a treatment option for body weight management and reduction of subcutaneous fat; however, reported studies have indicated that this treatment cannot reduce localized fat accumulation or fat cell hypertrophy or alleviate pain symptoms. Although no proven dietary treatment currently exists, nutrition plays a key role in managing lipedema. Certain dietary approaches such as ketogenic, low-carbohydrate, and modified Mediterranean diets have been explored for weight management and inflammation reduction in lipedema, with studies showing positive effects on body composition and pain. However, according to the current literature no evidence-based nutritional treatments or nutritional supplements are effective in this patient group. Nutritional therapy in lipedema is complicated by frequent comorbidities; therefore, precision nutritional therapy should be planned by evaluating the causes and consequences of the disease. In this review, we evaluated reported studies of current evidence-based clinical nutritional approaches to lipedema treatment.

Summary: Lipedema is a chronic disease characterized by the disproportionate and symptomatic accumulation of fat in the lower limbs and arms. Women with lipedema experience heaviness, fatigue and p...

Lipedema is a chronic disorder characterized by the symmetrical accumulation of subcutaneous adipose tissue, predominantly affecting women. Despite increasing recognition, the pathophysiological mechanisms underlying adipose tissue dysfunction in lipedema remain incompletely understood. This mini review combines current knowledge about adipose tissue biology in lipedema, highlighting recent discoveries, ongoing controversies, and future research directions. A comprehensive literature review was conducted focusing on adipose tissue-related research in lipedema with emphasis on pathophysiological mechanisms, cellular composition, and therapeutic implications. Recent studies reveal that lipedema adipose tissue exhibits distinct characteristics, including M2 macrophage predominance, stage-dependent adipocyte hypertrophy, progressive fibrosis, and altered lymphatic/vascular function. The inflammatory profile differs markedly from obesity, with an anti-inflammatory M2-like macrophage phenotype rather than the pro-inflammatory M1 response seen in classic obesity. Emerging evidence suggests lipedema may represent a model of “healthy” subcutaneous adipose tissue expansion with preserved metabolic function despite increased adiposity. Current research proposes menopause as a critical turning point, driven by estrogen receptor imbalance and intracrine estrogen excess. Lipedema represents a unique adipose tissue disorder distinct from obesity, characterized by specific cellular and molecular signatures. Current research gaps include the need for validated biomarkers, standardized diagnostic criteria, and targeted therapeutics. Future research should focus on elucidating the molecular mechanisms driving adipose tissue dysfunction and developing precision medicine approaches.

Lipedema is a chronic, progressive adipose tissue disorder that affects up to 10% of women and is characterized by disproportionate lower-limb fat accumulation, pain, edema, and resistance to conventional weight-loss approaches. Its pathophysiology involves a complex interplay of adipocyte hypertrophy, chronic inflammation, extracellular matrix fibrosis, mitochondrial dysfunction, and sex steroid imbalance, highlighting the need for disease-modifying therapies. This narrative review synthesizes mechanistic, translational, and clinical evidence linking metabolic, inflammatory, and fibrotic pathways to lipedema and tirzepatide's potential therapeutic relevance. Tirzepatide, a dual GLP-1 (Glucagon-Like Peptide-1)/GIP (Glucose-Dependent Insulinotropic Polypeptide) receptor agonist, has demonstrated unprecedented efficacy in obesity and diabetes, alongside pleiotropic actions on inflammation, fibrosis, and adipose remodeling. Mechanistic studies reveal favorable effects on macrophage polarization, cytokine signaling, extracellular matrix turnover, and thermogenesis, suggesting potential relevance to lipedema biology. Translational evidence from related fibro-inflammatory conditions such as steatohepatitis and heart failure further supports its antifibrotic and immunomodulatory plausibility. Although direct clinical evidence in lipedema is lacking, the convergence of mechanistic pathways provides a strong rationale to investigate tirzepatide as a disease-modifying candidate. If future clinical studies confirm these mechanisms, tirzepatide could represent a novel metabolic-hormonal therapy capable of modifying the natural course of lipedema.