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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 a lipodystrophic disease that is typically characterized by a marked increase in lower-body subcutaneous adipose tissue that is purported to have increased inflammation and fibrosis, impaired microvascular/lymphatic circulation and to be resistant to reduction by weight loss therapy. However, these outcomes have not been adequately studied. We evaluated body composition, insulin sensitivity, metabolic health and adipose tissue biology in women with obesity and lipedema (Obese-LIP) before and after moderate (~9%) diet-induced weight loss. At baseline, people with Obese-LIP had ~23% greater leg fat mass, ~11% lower android-to-gynoid ratio and ~48% greater insulin sensitivity (all P<0.05) than women matched on age, BMI and whole-body adiposity. In Obese-LIP, macrophage content and expression of genes involved in inflammation and fibrosis were greater, whereas lymph/angiogenesis-related genes were lower in thigh than abdominal subcutaneous adipose tissue. Weight loss improved insulin sensitivity and decreased total fat mass, with similar relative reductions in abdominal and leg fat masses, but without changes in markers of inflammation and fibrosis. These results demonstrate that affected adipose tissue in women with lipedema is characterized by increased inflammation and fibrogenesis, and alterations in lymphatic and vascular biology. Moderate diet-induced weight loss improves metabolic function and decreases lower-body adipose tissue mass.

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 adipose tissue condition that primarily affects women. Despite increasing recognition of lipedema, the condition remains poorly understood and lacks standardized diagnostic criteria or confirmatory tests. Variability in definitions and measurement across clinical and research settings impedes comparability across studies, constraining the evidence base needed to support future advances in clinical practice and patient care. To address challenges associated with inconsistent definitions and data collection, the Lipedema Foundation (LF) partnered with clinicians, researchers, and biostatisticians to develop a Lipedema Common Case Report Form (CCRF). The CCRF was designed to be a research data harmonization tool and is not intended to define diagnostic standards or guide clinical treatment decisions. Its development involved review of published lipedema clinical guidelines and collaborative work to define data elements and attributes for inclusion. When they existed, validated or standardized measures were incorporated directly. When no suitable standardized measures were available, an iterative and collaborative process was used to develop lipedema-specific Common Data Elements (CDEs). The initial version of the CCRF was piloted in participants with and without lipedema, and updates based on participant and clinician feedback were incorporated into the CCRF. A biostatistical review evaluated data completeness, quality, and structure, leading to additional refinements. The final Version 1 instrument consists of 682 CDEs organized into four classifications: (1) Core, (2) Supplemental Highly Recommended, (3) Supplemental, and (4) Exploratory. The current version is prepared for dissemination in the field. By disseminating the CCRF broadly and encouraging adoption in all lipedema research beginning in 2026, including all newly initiated LF-funded projects, LF intends to evaluate its use with grantees and iterate systematically to achieve consistent and comparable data collection. The CCRF provides a structured framework for harmonized data collection that may facilitate comparability across studies and support future development of standardized diagnostic and research methodologies.