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Lipedema is a chronic, estrogen-sensitive adipose tissue disorder characterized by disproportionate subcutaneous fat accumulation, fibrosis, inflammation, and resistance to fat mobilization. Despite its high prevalence, lipedema remains poorly understood and frequently misdiagnosed. This narrative review proposes a novel pathophysiological model in which menopause acts as a critical turning point in the progression of lipedema, driven by estrogen receptor imbalance (ERβ predominance over ERα), intracrine estrogen excess, and adipose tissue dysfunction. We demonstrate how menopauseinduced estrogen deficiency amplifies adipose tissue dysfunction by suppressing ERα signaling, enhancing ERβ activity, and disrupting mitochondrial function, insulin sensitivity, and lipid oxidation. Concurrently, the upregulation of aromatase and 17β-HSD1, combined with the suppression of 17β-HSD2, sustains localized estradiol excess, perpetuating inflammation, fibrosis, and immune dysregulation. The molecular signature observed in lipedema closely mirrors that of other estrogen-driven gynecological disorders, such as endometriosis, adenomyosis, and uterine fibroids. Understanding these molecular mechanisms highlights the pivotal role of menopause as a catalyst for disease progression and provides a rationale for targeted therapeutic strategies, including hormonal modulation and metabolic interventions. This review reframes lipedema as an estrogen receptor– driven gynecological disorder, offering a new perspective to improve clinical recognition, diagnosis, and management of this neglected condition.

Lipedema, a chronic and progressive adipose tissue disorder, is characterized by disproportionate fat accumulation, primarily in the lower extremities, often leading to pain, bruising, and mobility impairment. Despite its significant prevalence and impact on quality of life, diagnosis remains challenging, frequently relying on clinical examination and patient history. Ultrasonography holds promise as a non-invasive diagnostic tool, offering insights into subcutaneous tissue characteristics. However, developing a standardized qualitative ultrasonographic classification for lipedema presents considerable challenges due to the heterogeneous nature of fat tissue, variability in disease presentation, and the subjective interpretation inherent in qualitative assessments. This article reviews the current diagnostic landscape of lipedema, explores the potential and limitations of ultrasonography, and critically examines the complexities involved in establishing a robust qualitative ultrasonographic classification. By outlining these challenges, we aim to guide future research towards more objective and standardized imaging criteria, ultimately improving the accuracy and consistency of lipedema diagnosis.

Adipose tissue, or “fat”, has become synonymous with obesity. The public discourse frames a desire to reduce or even banish this tissue at almost every turn, with reasons ranging from aesthetics to health improvements. During decades of research into the development of adipose tissue-reducing interventions, there has also been an increasing acknowledgement and understanding of the physiological necessity for adipose tissue. Functional adipose tissue contributes to overall health due to its role in an incredibly diverse array of processes. For that reason, dysfunction in this tissue continues to be linked to a wide variety of pathologies, from infection to cancer and everything in between. In this book, we gather expert input from those currently expanding this field to provide insight into the importance of adipose tissue.

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 abnormal accumulation of adipose tissue, predominantly observed in women, characterised by symmetrical fat deposition and tactile sensitivity in the extremities, affecting both sides of the body. This condition can lead to significant pain, impairing daily activities and causing substantial discomfort.

Background: Postoperative fibrosis is a common and significant complication following liposuction for lipedema, often leading to tissue induration, pain, and compromised aesthetic results. This fibrosis can jeopardize the overall success of the procedure by reducing skin elasticity and altering the intended body contour.Objective: This study aims to evaluate the efficacy of early shockwave therapy (SWT) initiated 1 week after surgery to reduce postoperative fibrosis and preserve the functional and aesthetic outcomes of liposuction in lipedema patients. Methods: A prospective study was conducted on 50 female patients with stage II–III lipedema who underwent power-assisted liposuction (PAL). Patients received SWT sessions three times per week for 3 weeks, starting 7 days postoperatively. Outcomes were compared to a control group of 25 patients who did not receive SWT. Primary endpoints included fibrosis severity assessed by ultrasound elastography, skin elasticity measurements, and patient-reported outcomes on pain and satisfaction. The SWT group exhibited a significant reduction in fibrosis (2.1 ± 0.3 vs 3.8 ± 0.5, p < .001), improved skin elasticity (1.5 ± 0.2 mm vs 1.0 ± 0.3 mm, p < .01), and lower pain scores (2.3 ± 0.8 vs 4.7 ± 1.2, p < .001) compared to the control group. Results: Patient satisfaction was also higher in the SWT group (92% vs 68%, p < .01). Conclusion: Early postoperative shockwave therapy is an effective and safe treatment to reduce fibrosis after liposuction for lipedema. By modulating fibroblast activity, reducing pro-inflammatory cytokines, and improving tissue perfusion, SWT preserves the surgical outcomes and enhances patient satisfaction. These findings suggest that integrating SWT into postoperative protocols could be a valuable strategy to optimize liposuction results in lipedema patients.

Objectives: This study aimed to examine the effects of a multimodal exercise program on edema, pain, exercise capacity, lower extremity muscle strength, and function in patients with lipedema.Methods: The patients diagnosed with lipedema were randomly assigned to either the exercise (n: 11) or control (n: 11) groups. The exercise group participated in supervised group exercises focusing on aerobic and strengthening, twice a week for 6 weeks. The control group received training on physical activity additionally lipedema management. Sociodemographic and clinical characteristics were recorded. Edema (circumference measurements and local tissue water-LTW%), pain intensity (Visual Analogue Scale-VAS) and pressure pain threshold (Algometer), functional exercise capacity (Six minute walk test-6MWT), lower extremity muscle strength (Handheld dynamometer), lower extremity muscle strength/endurance (Sit-to-stand test) and lower extremity function (Lower Extremity Functional Scale-LEFS) were evaluated.Results: In the exercise group, significant reductions in pain during rest, activity, and nighttime, 6MWT distance, quadriceps and hip muscle strength, lower extremity strength/endurance, and function were observed (p < .05). When comparing the groups, no significant differences were found (p > .05); however, clinically, there were differences in limb volumes, pain reduction, muscle strength, and functional improvements, with medium to large effect sizes.Conclusion: The main findings of this study highlight the benefits of structured multimodal exercises for patients with lipedema to improve pain, limb volumes, exercise capacity, lower extremity muscle strength, endurance, and functionality.Clinical trials number: NCT06811961.

Aims Lipedema is a condition often mistaken for other causes of limb swelling including lymphedema and obesity. Lipedema may have a unique metabolic profile. Interrogation of the metabolome is a strategy that could reveal unique biomarkers to distinguish lipedema from lymphedema and obesity. Methods Unbiased metabolomics was utilized to examine 38 BMI-matched overweight patients compared with patients with lipedema, lymphedema, and lipolymphedema. Machine learning identified biomarkers to distinguish diseases, and further examined in a validation cohort of 198 patients with each disorders. Adjustments were made for baseline clinical and demographic variables. Results Plasma metabolomics firstly revealed uric acid as a biomarker that performs well to distinguish between phenotypically similar diseases in patients with elevated BMI. In a validation cohort of 64 patients with lipedema, uric acid (5.05 mg/dL) was compared with 64 patients with lymphedema (5.4 mg/dl), and 70 overweight patients without these conditions (4.6 mg/dL, p<0.05). Uric acid-to-cystatin c ratio distinguished between all three groups (Lipedema: 5.2; Lymphedema: 6.3; overweight: 4.0, p<0.01); however, significance was lost after adjustment for renal function. Conclusion Metabolomic analysis revealed uric acid may differentiate between lipedema, lymphedema, lipolymphedema and obese individuals without those conditions. In a validation cohort, while uric acid was higher in lipedema and lymphedema, uric acid adjusted by cystatin c clearance revealed uric acid to be a less useful marker to distinguish lipedema from lymphedema in the context of renal insufficiency.

Lipedema is a chronic disease in adipose tissue affecting women. The distinctive body appearance in lipedema, often mistaken for obesity, may be detrimental to social life. In our online cross-sectional survey study, conducted from June to September 2021 among 245 women with lipedema, we found significantly more health-related stigma compared to an aged-matched general female population (N = 1872), leading to an overall lower quality of life. Conversely, strong social support was associated with better social and emotional functioning. As such, healthcare professionals must, even in the early stages, recognize this disease and address its impact on psychosocial health and well-being.

Lipedema is a painful disease of subcutaneous adipose tissue (SAT) in women. This study determined whether an advanced pneumatic compression device (APCD) improved lipedema SAT depth, swelling, and pain. Women with lipedema started 20–30 mm Hg compression leggings then were randomized to an APCD (Lympha Press Optimal Plus) group for 30 days (treatment; n = 22) or a no APCD (Control; n = 24) group. APCD treatment significantly reduced left leg volume (3D imaging, LymphaTech; p < 0.043) and fluid in the left (p = 0.0018) and right legs (p = 0.0476; SOZO, bioimpedance spectroscopy); controls showed no change. Treatment significantly decreased extracellular fluid (ECF) and intracellular fluid (ICF) in left (p = 0.0077; p = 0.0060) and right legs (p = 0.0476; p ≤ 0.025), respectively. Only ECF decreased significantly in the left (p < 0.0183) and right legs (p = 0.0009) in controls. SAT depth decreased significantly by ultrasound after treatment at the anterior (p ≤ 0.0234) and medial thigh (p ≤ 0.0052), medial knee (p ≤ 0.0002) and posterior calf (p ≤ 0.0118) but not in controls. All signs and symptoms of lipedema improved in the treatment group including swelling (p = 0.0005) and tenderness (pain) of right (p = 0.0003) and left legs (p < 0.0001); only swelling improved in controls (p = 0.0377). In total, 87.5% of RAND SF-36 quality of life improved after treatment (p ≤ 0.0351) compared to 37.5% in controls (p ≤ 0.0475). APCDs are effective treatment for lipedema.

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.

Background: Pain is a prevalent symptom in patients with lipedema predominantly impacting the lower extremities. This study aimed to evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] and vitamin B12 levels and neuropathic pain (NP) in patients diagnosed with lipedema. Methods and Results: A total of 243 patients with lipedema who had 25(OH)D and B12 levels measured in the past 6 months were included in this study. Participants were divided into two groups: Group 1 (N = 78) with NP scores ≥13 and Group 2 (N = 165) with NP scores <13. The Turkish version of the painDETECT questionnaire was used to assess the patients' NP symptoms. Pain levels were measured using the Visual Analog Scale (VAS) and pain threshold through algometric measurement. Group 1 had significantly higher palpation and spontaneous VAS scores, and pain threshold through algometric measurements than Group 2 (p < 0.05). No statistically significant difference was found between the groups regarding vitamin D levels being below 30 ng/mL or vitamin B12 levels being below 400 pg/mL (p > 0.05). Conclusions: No association was found between NP and 25(OH)D or B12 levels in patients with lipedema.

Background: Bioimpedance spectroscopy (BIS) is commonly used for the detection and monitoring of lymphedema and potentially lipedema. BIS measures limb electrical resistance, which decreases with fluid accumulation in these conditions. R0, the index of extracellular fluid and lymph accumulation, is typically estimated using Cole modeling, but technical and biological factors can affect accuracy.Methods: Participants with clinically affirmed bilateral leg lymphedema, lipedema, self-ascribed swelling, and healthy controls were included in this study. Impedance measurements were taken using a stand-on BIS device, and R0 was estimated using both the Cole modeling method and a regression approach. Quality of data fitting was assessed visually and statistically.Results: Control participants were younger and lighter compared with the clinical groups. The regression method was able to analyze 100% of participant data, whereas the Cole method was successful in only 80%–88% of cases in the lymphedema and lipedema groups. Additionally, the regression approach provided better curve fitting accuracy for all participants.Conclusion: The regression method offers a robust alternative for estimating R0 values in BIS data, especially in lower limb assessments where data analysis is challenging. The small difference between methods in absolute R0 values (2.5%) has minimal practical implications, suggesting interchangeability in data analysis. The Cole method showed poorer performance, particularly in participants with lymphedema, possibly due to differences in water proportions and limb size. Overall, the regression method can be effectively used in clinical practice for estimating R0 values in BIS data, offering a more accurate and reliable approach than traditional Cole plotting methods.

Lipoedema is a loose connective tissue disease primarily affecting women characterized by an abnormal build-up of painful fat in the legs and arms. In healthcare, lipoedema is often confused with obesity, and today, diagnostic tools and standardized guidelines for adequate treatments are lacking. Still, research on how affected women manage their health problems and whether they are satisfied with their care remains sparse. Therefore, this study aimed to contribute knowledge on healthcare experiences, and their use and self-reported effects of self-care and treatments among women with lipoedema.

Lipedema is a chronic disorder characterized by disproportionate fat accumulation in the extremities, predominantly affecting women. Unlike obesity, lipedema might be associated with a lower prevalence of metabolic alterations despite often coexisting with overweight or obesity. Fat distribution pla …

IntroductionLipedema is a chronic and progressive adipose tissue disorder that predominantly affects women. However, despite its high prevalence and severe negative impact on quality of life, it remains significantly underdiagnosed. The aim of this study was to assess the knowledge and awareness of …

Lipedema is characterized by fat accumulation in the limbs, sparing the trunk, hands, and feet. Its etiology remains uncertain, but may be related to genetic and female hormones. Several theories suggest an association with chronic inflammation and fibrosis. Pain, spontaneous bruising, and increased diameter of the affected areas are the most frequent signs and symptoms. Diagnosis is primarily clinical, but frequently supported by imaging techniques, including ultrasound, magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DEXA), and lymphoscintigraphy to differentiate lipedema from other similar conditions. This study retrospectively analyzed ultrasonographic images of 34 female patients, clinically diagnosed with lipedema and correlated structural patterns with different stages of inflammation and fibrosis in the dermis and subcutaneous tissue. The images were obtained in 2024 using high-frequency linear transducers (12 - 15 MHz). The findings enabled the identification of potentially characteristic changes for the development of a classification that may assist in diagnosis, treatment, and monitoring of this condition. However, while ultrasonography has already been incorporated into routine medical practice to investigate lipedema, prospective and comparative multicenter studies that correlate ultrasound findings with the clinical stage of the disease are necessary to validate the applicability of this approach.

Background: Lipedema is an adipose tissue disorder in women, with an abnormal fat deposition in lower limbs and occasionally upper limbs. The condition is characterized by pain, bruising, heaviness, and mobility impairment. Objectives: This study aims to evaluate the effects of a modified Complete Decongestive Therapy protocol using the Godoy Method in the postoperative period following lipedema surgery. Methods: In total, 293 participants who underwent liposuction for lipedema were studied. The postoperative physiotherapy protocol included Godoy cervical stimuli, Manual Lymphatic Drainage based on Godoy maneuvers, mechanical lymphatic drainage with RAGodoy®, compression with bandages, skin care, and therapeutic education. Results: This study found that the number of physiotherapy sessions significantly reduced pain (p = 0.000) and other complications (p = 0.007) and increased mobility (p = 0.003). The number of physiotherapy sessions showed significant differences in pain intensity at 90 days posttreatment (p = 0.000). In total, 47.24% of the participants became functionally independent on the third day of the physiotherapy intervention (p = 0.003). A total of 40.96% of the participants developed some complications, although a relationship between inadequate compression and the occurrence of complications was also found in 36.52% of patients. Conclusions: The success of surgical treatment for lipedema not only depends on the surgery itself but also on the proper management of the patient in the perioperative period to minimize complications and prevent recurrence. The Complete Decongestive Therapy protocol modified with the Godoy Method showed effects on pain reduction, mobility increase, edema reabsorption, and prevention of complications, consequently enhancing functionality and quality of life for patients undergoing lipedema surgery.