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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.

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.

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.

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 ."

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.

Lipedema is a chronic, progressive disorder marked by the abnormal accumulation of subcutaneous adipose tissue, predominantly in the lower body and almost exclusively affecting women. In recent years, the off-label use of gestrinone - a synthetic steroid with androgenic, antiprogestogenic, and weak estrogenic activity, originally approved only for endometriosis - has gained attention as a potential therapy for lipedema, particularly in the form of subcutaneous implants. This systematic review aimed to assess the efficacy and safety of gestrinone for this indication. A systematic literature search was conducted in PubMed, MEDLINE, Cochrane Library, and LILACS; clinical trial registries (ClinicalTrials.gov and Brazilian Registry of Clinical Trials (ReBEC)); as well as national and international clinical guidelines and expert consensus documents published up to July 30, 2025, following PRISMA guidelines. Eligible studies included randomized trials, observational studies, systematic reviews, case series, and clinical guidelines. Study selection, data extraction, and quality assessment were performed independently by two reviewers, with a third resolving discrepancies. The search identified nine records across all databases, registries, and other sources. After removing one duplicate, eight unique records were screened. All four records from indexed databases underwent full-text assessment. After applying inclusion/exclusion criteria, no studies - randomized, observational, or otherwise - were identified that evaluated the use of gestrinone for lipedema. Likewise, no ongoing clinical trials were found. Clinical guidelines and position statements from professional societies and patient associations uniformly advise against the off-label prescription of gestrinone for lipedema, citing the absence of scientific evidence. There is no scientific basis for the use of gestrinone in the management of lipedema. Healthcare providers should rely on evidence-based treatments, including compression therapy, tailored physical exercise, nutritional counseling, and psychological support and restrict hormonal interventions to ethically approved research protocols.

BACKGROUND: Lipedema is a chronic, progressive and underdiagnosed condition characterized by bilateral, disproportionate and painful subcutaneous fat accumulation in extremities. Key symptoms include pain, heaviness and easy bruising. Surgical treatment, particularly liposuction, has shown excellent outcomes in symptom reduction and quality of life improvement. This study evaluates clinical outcomes in symptoms and aesthetic self-perception improvements in patients treated with selective combined liposuction (SCL). PATIENTS AND METHODS: A retrospective review of 126 female patients who underwent surgical treatment over a four-year period was performed. Selective tumescent liposuction combining power-assisted liposuction (PAL) with VASER (ultrasound-assisted liposuction) for proximal areas, especially the thighs. Demographic and clinical data, including BMI, medical history and comorbidities were analyzed. Symptoms such as pain, heaviness and edema, and body image perception were assessed preoperatively and six months postoperatively with a structured questionnaire. RESULTS: The mean patient age was 39 years, with a mean BMI of 27.2. The mean aspirated volume was 3270 mL per procedure. In 25.4% of the cases (n=32), a second procedure was required, with an average total aspirated volume of 5150 mL. Significant symptom improvement was observed: 89% reported reduced pain, 92% reduced heaviness, 82% reduced edema. Mobility limitations improved in 91% of patients, while 60% reported enhanced aesthetic perception of their extremities. Additionally, 68% of patients expanded their wardrobe postoperatively. CONCLUSIONS: Selective combined liposuction is a safe and highly effective technique for lipedema treatment, providing substantial symptom relief, improved body aesthetic self-perception, which leads to an improvement in the quality of life.

Lipoedema is a disease that affects women and is characterised by an abnormal accumulation of fatty tissue, with pain and a feeling of heaviness in the lower limbs. Approximately 30 % of patients also have involvement of the upper limbs. The cause of lipoedema is unknown, but familial clustering of the condition suggests an underlying genetic cause. Oestrogen and hormonal changes appear to be involved, as the condition occurs predominantly in women and is linked to hormonal fluctuations. In Norway, women with lipoedema have had limited access to treatment within the public health service, and the condition is relatively unknown among Norwegian healthcare personnel. Internationally, the diagnosis and treatment of lipoedema are largely based on consensus, as there is a lack of definitive scientific evidence in relation to pathophysiology and treatment. This clinical review presents lipoedema diagnostics and treatment based on clinical experience and international published consensus statements.

INTRODUCTION: Lipedema is a chronic and progressive disease that predominantly affects women, characterized by a disproportionate increase in subcutaneous adipose tissue (AT), particularly in the lower limbs. It is associated with significant physical disability, chronic pain, thromboembolism, and psychosocial distress. Despite its profound impact on women's health and quality of life, lipedema remains underrecognized and insufficiently studied, with an estimated prevalence of approximately 10% among women worldwide. Although the exact etiology of lipedema remains unclear, emerging evidence suggests a multifactorial origin involving genetic predisposition, hormonal influences, and vascular dysfunction-all contributing to its development and progression. Current therapeutic options provide only partial symptom relief and remain noncurative, highlighting the urgent need for expanded research and improved management strategies. METHODS: A systematic review was conducted to assess the current understanding of lipedema pathophysiology and current treatment options. Research articles were sourced from PubMed, Web of Science, ScienceDirect, and Scopus databases. Over 100 studies were incorporated. RESULTS: This review provides a comprehensive overview of lipedema, encompassing its clinical features, pathophysiological mechanisms, diagnostic challenges, and current treatment modalities. Additionally, the review discusses whether the molecular and metabolic differences between abdominal and femoral AT depots mirror those observed in classical obesity. CONCLUSIONS: Multidisciplinary, research-informed care is essential for managing lipedema, combining conservative therapies, tailored exercise, and liposuction for advanced cases. More research to better understand the underlying pathophysiology is critical to developing targeted treatments, improving diagnostic accuracy, and informing standardized, evidence-based care.

Lipedema is an adipose tissue disorder that principally affects women and is frequently misidentified as obesity or lymphedema. There have been relatively few studies that have precisely defined the pathogenesis, epidemiology, and treatment approaches for lipedema. However, successfully recognizing lipedema as a distinct condition is important for proper management. This review aimed to examine the existing literature on the epidemiology, pathogenesis, clinical presentation, differential diagnosis, and treatments for lipedema. The current research indicates that lipedema appears to be a clinical entity related to genetic factors and fat distribution, although distinct from lymphedema and obesity. Some available treatments include complex decongestive physiotherapy, liposuction, and laser-assisted lipolysis. The management of lipedema is complex and differs from that of lymphedema. Further high-quality randomized controlled trials are urgently needed to continue advancing our understanding of this often neglected disease and exploring optimal medical and surgical treatment regimens tailored specifically for lipedema patients. In summary, despite frequent misdiagnosis, enhanced recognition, and research into customized therapeutic strategies for this poorly characterized but likely underdiagnosed disorder represent promising steps forward. Level of evidence  N/A.

Lipoedema is a chronic and painful fat disorder that occurs almost exclusively in women. It mainly affects the legs and sometimes the arms. The condition not only causes physical complaints but also has a major impact on daily functioning and quality of life. Despite this, lipoedema is still poorly understood and appropriate care is often lacking. In this dissertation, we reviewed the existing literature on the functioning of people with lipoedema. In addition, we explored how they experience living with the condition, the challenges they face in managing it, and how healthcare professionals can provide better support. The studies show that lipoedema is more than meets the eye. Earlier research mainly focused on the physical aspects, while psychosocial issues such as shame, stigmatisation, and reduced social participation are equally important. Participants emphasised the need for personal guidance, access to specialised care, and reliable, evidence-based information. To address these needs, we developed a new self-management intervention: SELF-MANAGING your lipoedema. This programme helps people cope more effectively with their condition, take control of daily life, and set achievable goals together with their healthcare professionals. This dissertation highlights that good care for people with lipoedema must go beyond symptom management. A holistic approach is needed, alongside better knowledge and training for healthcare professionals, and policies that promote collaboration across disciplines. Such improvements can truly enhance the quality of life of those living with lipoedema.

PURPOSE OF REVIEW: This review aims to provide an overview of the current evidence on the efficacy, also considering the anti-inflammatory properties and safety of very low-calorie ketogenic diet (VLCKD) as a potential treatment for lipedema, particularly in the context of obesity. RECENT FINDINGS: Lipedema is a chronic disease characterized by abnormal and painful fat buildup on the legs and/or arms. It is often misdiagnosed as obesity or lymphedema. However, although lipedema and obesity can coexist, unlike obesity, lipedema usually affects the legs and thighs without affecting the feet or hands, and the abnormal deposition of adipose tissue in lipedema is painful. The current lifestyle interventions are often unsuccessful in the management of lipedema. There is no consensus on the most effective nutritional approach for managing lipedema. Recent studies have suggested that VLCKD may be an effective treatment for lipedema, demonstrating that it is also superior to other nutritional approaches such as Mediterranean diet or intermittent fasting. Lipedema is a chronic and debilitating disease characterized by abnormal and painful accumulation of adipose tissue in the legs. VLCKD has been shown to be an effective treatment for lipedema, especially in the context of obesity, due to its anti-inflammatory properties. However, further research is needed to determine the long-term safety and efficacy of VLCKD as a treatment for lipedema.

BACKGROUND: Diagnosing lipedema remains a challenge due to its heterogeneous presentation, co-existing diseases, and the lack of objective diagnostic imaging. OBJECTIVE: This systematic review aims to outline the currently available diagnostic imaging methods to characterize lipedema in the legs along with their diagnostic performance. METHODS: PubMed, Embase, Google Scholar, Scopus, and Web of Science were searched. The quality assessment of diagnostic accuracy studies (QUADAS) tool was used for quality assessment. RESULTS: Thirty-two studies describing a total of 1154 patients with lipedema were included for final analysis. Features for lipedema have been defined using ultrasound (increased subcutaneous adipose tissue), lymphoscintigraphy (slowing of the lymphatic flow and a frequent asymmetry between the lower extremities), computed tomography (symmetrical bilateral soft tissue enlargement without either skin thickening or subcutaneous edema), magnetic resonance imaging (increased subcutaneous adipose tissue), MR lymphangiography (enlarged lymphatic vessels up to a diameter of 2 mm), and dual-energy X-ray absorptiometry (fat mass in the legs adjusted for body mass index (BMI) ≥ 0.46 or fat mass in the legs adjusted for total fat mass ≥ 0.384). CONCLUSION: The diagnostic performance of currently available imaging modalities for assessing lipedema is limited. Prospective studies are needed to evaluate and compare the diagnostic performance of each imaging modality. Imaging techniques focusing on the pathogenesis of the disease are needed.

Lymphedema and specifically cancer-related lymphedema is not the main focus for both patients and physicians dealing with cancer. Its etiology is an unfortunate complication of cancer treatment. Although lymphedema treatments have gained an appreciable consensus, many practitioners have developed and prefer their own specific protocols and this is especially true for conventional (manual) versus surgical treatments. This collection of presentations explores the incidence and genetics of cancer-related lymphedema, early detection and monitoring techniques, both conventional and operative treatment options, and the importance and role of exercise for patients with cancer-related lymphedema. These assembled presentations provide valuable insights into the challenges and opportunities presented by cancer-related lymphedema including the latest research, treatments, and exercises available to improve patient outcomes and quality of life.

A large and growing body of research suggests that the skin plays an important role in regulating total body sodium, challenging traditional models of sodium homeostasis that focused exclusively on blood pressure and the kidney. In addition, skin sodium may help to prevent water loss and facilitate macrophage-driven antimicrobial host defense, but may also trigger immune dysregulation via upregulation of pro-inflammatory markers and downregulation of anti-inflammatory processes. We performed a systematic search of PubMed for published literature on skin sodium and disease outcomes and found that skin sodium concentration is increased in patients with cardiometabolic conditions including hypertension, diabetes, and end-stage renal disease; autoimmune conditions including multiple sclerosis and systemic sclerosis; and dermatologic conditions including atopic dermatitis, psoriasis, and lipedema. Several patient characteristics are associated with increased skin sodium concentration including older age and male sex. While animal evidence suggests that increased salt intake results in higher skin sodium levels, there are conflicting results from small trials in humans. Additionally, limited data suggest that pharmaceuticals such as diuretics and SGLT-2 inhibitors approved for diabetes, as well as hemodialysis may reduce skin sodium levels. In summary, emerging research supports an important role for skin sodium in physiologic processes related to osmoregulation and immunity. With the advent of new non-invasive MRI measurement techniques and continued research on skin sodium, it may emerge as a marker of immune-mediated disease activity or a potential therapeutic target.

Lymphangiogenesis is the mechanism by which the lymphatic system develops and expands new vessels facilitating fluid drainage and immune cell trafficking. Models to study lymphangiogenesis are necessary for a better understanding of the underlying mechanisms and to identify or test new therapeutic agents that target lymphangiogenesis. Across the lymphatic literature, multiple models have been developed to study lymphangiogenesis in vitro and in vivo. In vitro, lymphangiogenesis can be modeled with varying complexity, from monolayers to hydrogels to explants, with common metrics for characterizing proliferation, migration, and sprouting of lymphatic endothelial cells (LECs) and vessels. In comparison, in vivo models of lymphangiogenesis often use genetically modified zebrafish and mice, with in situ mouse models in the ear, cornea, hind leg, and tail. In vivo metrics, such as activation of LECs, number of new lymphatic vessels, and sprouting, mirror those most used in vitro, with the addition of lymphatic vessel hyperplasia and drainage. The impacts of lymphangiogenesis vary by context of tissue and pathology. Therapeutic targeting of lymphangiogenesis can have paradoxical effects depending on the pathology including lymphedema, cancer, organ transplant, and inflammation. In this review, we describe and compare lymphangiogenic outcomes and metrics between in vitro and in vivo studies, specifically reviewing only those publications in which both testing formats are used. We find that in vitro studies correlate well with in vivo in wound healing and development, but not in the reproductive tract or the complex tumor microenvironment. Considerations for improving in vitro models are to increase complexity with perfusable microfluidic devices, co-cultures with tissue-specific support cells, the inclusion of fluid flow, and pairing in vitro models of differing complexities. We believe that these changes would strengthen the correlation between in vitro and in vivo outcomes, giving more insight into lymphangiogenesis in healthy and pathological states.

Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop.