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Lymphedema and Lipedema are chronic disorders that are often misdiagnosed, leading to complications ranging from infection to impaired mobility. While the genetic basis of lymphedema is well characterized, the genetic contributions to lipedema remain unclear despite clear familial hereditary patterns. This review examines current knowledge on the genetic foundations of both conditions, examining established causative genes in lymphedema and emerging evidence of heritability in lipedema. It also evaluates the role of genetic testing in diagnosis and classification. By emphasizing established findings and highlighting ongoing gaps, this review supports efforts to refine diagnosis and guide therapeutic development.

Lipedema is a chronic and progressive adipose tissue disorder characterized by disproportionate fat accumulation, microvascular dysfunction, chronic inflammation, and progressive fibrosis. Despite its prevalence and significant impact on quality of life, current therapeutic approaches remain largely symptomatic and fail to address the underlying biological mechanisms of the disease. Emerging evidence suggests that lipedema should be understood as a multifactorial condition involving genetic susceptibility, endothelial alterations, immune dysregulation, and extracellular matrix remodeling. In this context, pharmacological strategies targeting these pathways have gained increasing attention. Metformin, through activation of AMP-activated protein kinase (AMPK), exerts antifibrotic and immunometabolic effects, including inhibition of TGF-β signaling, reduction of extracellular matrix deposition, and modulation of adipose tissue inflammation. In parallel, incretin-based therapies, particularly glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/GIP agonists such as tirzepatide, have demonstrated pleiotropic effects that extend beyond weight reduction, including improvements in metabolic homeostasis, reduction of systemic inflammation, and enhancement of endothelial function. These therapies appear to act through complementary mechanisms, with metformin primarily targeting tissue remodeling and fibrosis, and incretin-based therapies exerting broader systemic effects on metabolism, inflammation, and vascular integrity. This review proposes a hypothesis-generating mechanistic framework, supporting a shift from weight-centric and symptomatic approaches toward disease-modifying strategies. Although current evidence in lipedema is largely indirect, the convergence of experimental and clinical data provides a strong rationale for further investigation. Future studies should focus on evaluating combined therapeutic approaches and identifying biomarkers that reflect fibrosis, inflammation, and microvascular dysfunction, with the aim of developing targeted and personalized treatments for this complex disorder.

Background/Objectives: Non-invasive radiofrequency (NIRF) therapy is increasingly used in physical rehabilitation. However, its efficacy across differ...

Lymphedema is a common, debilitating condition that challenges treatment efforts. The primary aim of treatment is to debulk the affected areas, providing relief without further damaging tissues or causing undesirable cosmetic outcomes. Liposuction has become a popular treatment for end-stage extremity lymphedema, yet there is no consensus on the most effective technique. Current practices include a range of methods such as dry, wet, superwet, laser-assisted, water-assisted, and power-assisted liposuction. Dry liposuction has sparked controversy, primarily due to concerns that it might be less gentle, and therefore potentially more harmful, than wet liposuction. Contrary to this, we posit that dry liposuction is a viable, low-risk alternative that minimizes the risk of tissue and lymph vessel damage while providing excellent and durable outcomes. This assertion is supported by current literature. In this video article, we present our systematic, step-by-step approach to performing dry liposuction for end-stage lymphedema, illustrating its efficacy and safety. Our personal experience is that patients experience significant reductions in limb volume and report high satisfaction rates, demonstrating that dry liposuction is both effective and reliable for the long-term management of end-stage lymphedema. LEVEL OF EVIDENCE V: 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 a chronic condition characterized by abnormal fat accumulation, primarily in the lower extremities, affecting mostly women. Despite improvements in diagnosis and treatment, lipedema is often misdiagnosed as obesity or lymphedema. Patients with obesity and lipedema propose a distinct clinical challenge in treating both diseases. Improved recognition and understanding are necessary to enhance diagnosis and treatment outcomes. PURPOSE OF THIS REVIEW: Lipedema is thought to be hormonally driven, often manifesting during puberty, pregnancy, or menopause. It presents as disproportionate fat accumulation in the lower body, often with microvascular changes. Misdiagnosis as obesity or lymphedema leads to ineffective treatments like weight loss programs and bariatric surgery. Effective management involves both conservative and surgical approaches, as well as a tailored strategy for patients with both lipedema and obesity. The focus of this review is to summarize the current literature addressing adequate treatment regimens for patients with both diseases and based on the literature we propose a treatment protocol. CONCLUSION: Patients with concurrent lipedema and obesity propose a distinct clinical challenge, in which early recognition can benefit adequate treatment. A combination of conservative measures and surgical options, particularly liposuction and/or bariatric and metabolic surgery, can be beneficial in treating patients with both diseases. However future research is needed to assess the effect of different treat regimens.

Lipedema is a chronic, progressive adipose tissue disorder characterized by disproportionate subcutaneous fat accumulation, pain, edema, and resistanc...

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.

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 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.

SUMMARY OBJECTIVE: The aim of this study was to characterize global scientific output on lipedema from 2000 to 2025 and identify emerging thematic trends, with emphasis on the emergence of immunological research. METHODS: Publications indexed in Google Scholar, PubMed, Crossref, OpenAlex, and Scopus were retrieved using the terms "lipedema" OR "lipoedema." Records were deduplicated by normalized title matching and DOI cross-referencing. Bibliometric indicators computed included publication volume, citation metrics, field h-index, exponential growth rate, geographic distribution, author metrics, specialty classification (journal-name keyword matching supplemented by OpenAlex concept tags), and immunological content (regular-expression pattern matching against a predefined term list). RESULTS: A total of 942 unique publications were identified, accumulating 13,688 citations (field h-index=60; mean 14.5 citations per article; median 2 citations per article). Annual output grew from below 12 per year through 2009 to 145 in 2025, with a doubling time of 3.6 years (R2=0.90; p<0.001). The United States, Germany, and Brazil were the most productive countries. Karen Lynn Herbst (USA) was the most influential researcher (46 papers; h-index=20; 1,586 citations). Lymphology and phlebology formed the dominant classifiable domain (17.1%), with 69.3% of publications spanning multiple disciplines. Publications with immunological content totaled 30 (3.2%), grew from essentially zero before 2019 to 4.8% of annual output in 2025, and received higher mean citations than non-immunological articles (16.6 vs. 14.5). CONCLUSION: Lipedema research is undergoing rapid exponential expansion driven by growing global recognition of a historically neglected condition. The accelerating immunological trend, with consistently higher citation impact, indicates an accelerating paradigm shift toward chronic adipose tissue inflammation as a unifying pathophysiological framework.

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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 disorder characterized by a disproportionate accumulation of subcutaneous adipose tissue in the extremities, typically sparing the hands and feet. It is commonly associated with pain, hypersensitivity, easy bruising, edema, and fibrotic nodules. Despite growing awareness, there is still no consensus on evidence-based therapeutic approaches. This integrative review aimed to identify physical therapy strategies described in the scientific literature for the assessment and conservative management of lipedema. Searches were conducted in the PubMed/MEDLINE, BVS, PEDro, Embase, and Cochrane databases, followed by critical appraisal and evidence synthesis, with applicable PRISMA-ScR checklist items used as a reporting guide for the study selection process. The findings indicate that physical therapy plays a key role in conservative treatment, particularly through complete decongestive therapy, compression therapy, exercise, manual therapy, and electrophysical agents. These interventions show potential benefits in reducing pain, improving functional capacity, controlling edema, and preventing disease progression. However, the available evidence remains limited, underscoring the need for more robust clinical trials to support evidence-based physical therapy practice in the treatment of lipedema.Keywords: lipedema; physical therapy modalities; conservative treatment