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BACKGROUND: Lipedema is a chronic, progressive adipose tissue disorder that predominantly affects women and is characterized by disproportionate fat accumulation, pain, and edema. Hormonal fluctuations are frequently reported as triggers or modulators of symptoms, but the impact of exogenous hormones, especially hormonal contraceptives, remains poorly defined. OBJECTIVE: This study aimed to investigate the association between hormonal contraceptive use and the presence, severity, and self-reported worsening of lipedema symptoms in Brazilian women. METHODS: This observational, cross-sectional study was conducted at Amato - Instituto de Medicina Avançada using a structured online questionnaire applied between August and November 2025. We included women aged 18 years or older, residing in Brazil, with suspected or confirmed lipedema who provided electronic consent and completed core sections on lipedema symptoms, hormonal history, and contraceptive use. Questionnaires with less than 50% of core items answered, duplicate entries, and biologically implausible values were excluded. Symptom (0-8) and quality of life (0-15) scores were calculated. Self-reported changes in symptoms after starting hormonal contraceptives were analyzed as a four-level variable and as a binary worsening variable. Free text on side effects and timing of onset was categorized with natural language processing. Statistical analyses included chi-squared tests, Spearman correlations, and logistic and linear regression. RESULTS: A total of 637 women were included (mean age 41.8±8.7 years; mean body mass index (BMI) 28.9±6.4 kg/m²); 77.1% had a confirmed diagnosis of lipedema and 92.3% were current or previous users of hormonal contraceptives. Among users, 58.8% reported symptom worsening after starting contraceptives (34.5% severe; 24.3% slight), 40.3% reported no change, and 0.9% reported improvement (p<0.001). Free text analysis showed that 15.1% reported onset of lipedema symptoms temporally coinciding with contraceptive initiation. In multivariable analysis, a higher baseline symptom score was the strongest independent predictor of worsening, while duration of contraceptive use was not associated with risk. Pain intensity and BMI were the main independent predictors of quality of life impact. CONCLUSIONS: In this large sample of Brazilian women with suspected or confirmed lipedema, hormonal contraceptive use was frequently associated with self-reported worsening of symptoms, and a substantial minority reported symptom onset around contraceptive initiation. Women with higher baseline symptom burden appeared particularly vulnerable. These findings support individualized contraceptive counseling for women with lipedema and highlight the need for prospective studies with objective measures to clarify causality and mechanisms.

Obesity is increasingly recognized not only as a metabolic disorder, but also as a state of chronic low-grade inflammation that predisposes to systemic complications. Within this context, Dercum's disease (DD), or adiposis dolorosa, emerges as a rare yet debilitating disorder characterized by painful subcutaneous lipomas, most commonly affecting middle-aged women. Despite its clinical impact, DD remains underdiagnosed and is often misclassified as lipedema, fibromyalgia, or lipomatosis, complicating prevalence estimates and hindering the development of targeted interventions. Current evidence suggests that DD represents a distinctive model of inflammatory obesity, where adipose tissue actively contributes to pain generation rather than serving as a passive fat reservoir. Histological and molecular findings point to adipose tissue dysfunction, immune cell infiltration, and elevated secretion of pro-inflammatory adipokines, signals which appear to fuel systemic low-grade inflammation, perineural immune interactions, and nociceptor sensitization. Peripheral mechanisms further shape the clinical phenotype. While familial clustering suggests possible genetic contributions, no definitive markers have been identified, and the role of obesity-induced epigenetic modifications remains unexplored. Therapeutic strategies remain largely symptomatic, including analgesics, antidepressants, physical rehabilitation, and surgical excision of lipomas, whereas molecularly targeted and diet-based interventions are still experimental. This article discusses the pathophysiology of DD, current treatments, and future perspectives, emphasizing that advancing patient registries, omics-based analyses, and interdisciplinary clinical trials will be crucial to elucidate disease mechanisms and guide novel therapies. Improved understanding of DD may not only enhance patient care, but also provide broader insights into the interplay between obesity, inflammation, and chronic pain.

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/Objectives: Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation and inflammation, predominantly affecting women. While recent evidence suggests a systemic pro-inflammatory state in lipedema, the role of diet in modulating inflammation remains underexplored. This study assessed the anti-inflammatory potential of a Mediterranean-style ketogenic diet and its effects after 7 months of adherence on systemic inflammation markers (CRP and IL-6) in women with lipedema (n = 24) and a control group with overweight/obesity (n = 24). Methods: The Dietary Inflammatory Index (DII) was used to characterize the inflammatory potential of the diet throughout the intervention. Dietary intake was analyzed pre- and post-intervention, and anthropometric, body composition, and biochemical parameters were measured. Results: Beyond its beneficial effects on body composition (significant reductions in body weight, fat, leg circumferences, and visceral fat), the intervention diet also demonstrated anti-inflammatory potential. In lipedema, baseline diet showed a pro-inflammatory DII profile (DII/day = 3.04), which was reduced by about 1.5 points after the intervention (p = 0.008). When expressed per 1000 kcal, the DII values were markedly lower for both baseline (DII = 0.22) and intervention diet (DII = ~0.01). Following the intervention diet, reduction in CRP (-0.39, p = 0.016) and IL-6 levels (-0.33, p = 0.034) in lipedema were observed. A significant positive association was observed between the intervention diet's DII and CRP (r = 0.55, p = 0.005), and between the baseline diet's DII and IL-6 (r = 0.50, p = 0.013) in lipedema group. Conclusions: These findings suggest that ketogenic diet rich in anti-inflammatory and antioxidant nutrients can reduce systemic inflammation in lipedema patients, independently of caloric restriction.

BACKGROUND: Lipedema is a chronic disorder of adipose tissue that predominantly affects women and is frequently misdiagnosed as obesity or lymphedema. Traditionally associated with the lower extremities, lipedema can also involve the abdominal region, although there are currently no established diagnostic criteria for abdominal lipedema. This study aims to propose a diagnostic algorithm for abdominal lipedema based on clinical features, macroscopic observations, and ultrasound findings. METHODS: This retrospective study analyzed data from 327 patients treated between March 2018 and March 2024 for lipedema, including those with abdominal involvement. Clinical evaluations, ultrasound imaging, and surgical outcomes were examined to assess the prevalence and characteristics of abdominal lipedema. Patients were classified based on lipedema severity, and criteria for abdominal lipedema diagnosis were established through clinical and imaging data. RESULTS: The study identified that abdominal involvement increases with the severity of lipedema, with 31% of patients with stage II lipedema and 70% of those with stage III lipedema exhibiting abdominal manifestations. The proposed diagnostic algorithm includes maximum, major, and minor criteria, such as symmetrical fat deposition, pain, and non-responsiveness to diet and exercise. Specific threshold values for each category were defined to establish the diagnosis. The findings highlight the existence of both ascending (from legs to abdomen) and descending (from arms to abdomen) centripetal progression patterns, challenging traditional notions that limit lipedema to the extremities CONCLUSION: Abdominal lipedema is a significant and underrecognized manifestation of the condition, requiring specific diagnostic criteria to ensure accurate diagnosis and appropriate treatment. The study proposes a diagnostic framework based on clinical and imaging features that can improve the recognition and management of abdominal lipedema. Multidisciplinary treatment approaches, including both conservative measures and surgical interventions such as abdominoplasty and liposuction, are recommended to improve patient outcomes. 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 .

ObjectiveThe incidence of lipedema is poorly described due to its confusion with lymphedema. Patient education is crucial for treatment and prevention strategies but also for improving healthcare outcomes. This study assessed and compared the quality of English and Spanish online resources for patients suffering from lipedema using a multimetric approach.MethodsA deidentified Google search using the terms "lipedema" and "lipedema español" was conducted. The first 10 academic/organizational websites in each language were selected. Quality assessment was performed using the Patient Education and Materials Assessment Tool (PEMAT), Cultural Sensitivity Assessment Tool (CSAT), Simple Measure of Gobbledygook (SMOG), and facticity criteria to evaluate understandability and actionability, cultural sensitivity, readability, and factual quality, respectively.ResultsEnglish webpages scored 73.70% for understandability and 35.0% for actionability, while Spanish webpages scored 75.05% and 21.0%, respectively; no significant differences were found between languages in understandability (p = .970) and actionability (p = .895). A significantly higher proportion of Spanish resources was found to be culturally sensible than English resources (90% vs 70%; p < .001). However, no significant differences were found in the cultural sensitivity score (English 2.87 vs Spanish 3.01; p = .677). The grade reading level for Spanish materials was significantly lower compared to English materials (11.08 vs 13.45; p = .006). Factual quality was low across both languages according to the facticity framework, though English materials scored higher than Spanish (2.20 vs 1.00; p = .051).ConclusionOur results suggest that online English and Spanish materials on lipedema have inadequate actionability, facticity, and reading grade levels for patients. Nonetheless, the levels of understandability and cultural sensitivity are acceptable. Enhancing the quality of online health literature for lipedema patients presents an opportunity to alleviate psychosocial burdens and address misconceptions.

Lipoedema (lipalgia) is a condition that is often underdiagnosed or misdiagnosed as obesity or lymphoedema, which can result in mismanagement of treatment leading to poor mental and physical outcomes. It is a condition that is predominately seen in those assigned female at birth and rarely identified at an early age. Inconsistencies regarding criteria used for diagnosis and staging has led to challenges in the reliability of treatment options available for people with the condition. Poor diagnosis can substantially impact on a person's quality of life in terms of mental health, physical health and finances. Lipoedema has different stages and classifications according to visual characteristics. Recommended developments of practice include the setting up of a diagnostic criteria to identify key symptoms of lipoedema, which can help practitioners consider effective treatment options alongside diet, exercise, compression therapy and skin care as part of the overall treatment plan.

ObjectiveTo assess the relationship between disease severity in lipedema and tissue stiffness measured using shear wave elastography (SWE) concerning pain threshold and quality of life as well as determine differences in subcutaneous tissue stiffness between patients with lipedema and healthy subjects.Methods71 participants were subjected to measurements using subcutaneous tissue elastic modulus with SWE imaging of lower limbs at three anatomical levels. The participants were divided into two groups: those diagnosed with lipedema (Group (1) (n = 35) and healthy subjects (Group (2) (n = 36). Patients with lipedema were categorized into three stages based on disease severity. Pain levels were assessed using the visual analog scale (VAS), pain pressure threshold through algometric measurement within lipedema stages, and quality of life using EQ-5D quality of life scale in all groups.ResultsNo statistically significant differences in age, BMI, right and left three-zone elastic modulus averages were observed between the groups within BMI levels of 25-29.9 and ≥30 kg/m2 (p > .05). Same BMI group, according to lipedema stage, the mean elastic modulus of the right pretibial region in stage 2 cases was significantly higher than in stage 1 cases within BMI levels of 25-29.9 kg/m2 (p < .05). The all-region algometric measurements in Group 1 were significantly lower than those in Group 2, within BMI levels of 25-29.9 kg/m2 and ≥30 kg/m2. The average spontaneous VAS scores in Group 1 were significantly higher than those in Group 2 within the same BMI (p < .05). The VAS palpation scores in Group 1 exceeded those in Group 2 for BMI ≥30 kg/m2 (p < .05). No significant difference in VAS palpation scores was observed for BMI 25-29.9 kg/m2 (p > .05). The EQ-5D VAS scores of the control group were significantly lower than those of stage 1, 2, and 3 cases (p < .05).ConclusionsIn lipedema, pain characteristics may be more distinctive than the elastic properties of adipose tissue. Increased algometric measurements may reflect a specific objective sensation.

BackgroundTo evaluate kinesiophobia and its relationship with disease-related characteristics and quality of life in lipedema patients.MethodsIn this descriptive case-control study, 40 lipedema patients and 40 participants in the control group were included. All participants were evaluated in terms of body mass index (BMI), pain numeric rating scale (NRS) and pain threshold (PT) scores, kinesiophobia (Tampa Scale for Kinesiophobia - TSK), lower extremity functional scores (Lower Extremity Functional Scale - LEFS), and health-related quality of life (Nottingham Health Profile - NHP) scores. Additionally, the lipedema patients were evaluated in terms of extremity volumes, and total and mean lower extremity fat mass by dual-energy X-ray absorptiometry.ResultsHigh kinesiophobia was detected in 78% of the lipedema patients and 55% of the control group (p = .033). TSK (p = .048), NRS (p = .001), and NHP total scores (p = .041) were higher and PT scores (p = .007) were lower in lipedema patients compared to the control group. No difference was found between lipedema patients with high and low kinesiophobia in terms of fat mass or extremity volumes. A positive correlation was found between TSK score, NHP total score (r = 0.356, p = .024), NHP physical activity (ρ = 0.403, p = .010) and NHP energy (ρ = 0.436, p = .005) subscale scores.ConclusionKinesiophobia is highly prevalent in lipedema patients, regardless of disease-related data and affecting the quality of life of the patients, negatively.

BACKGROUND: Lipedema is an adipose tissue disorder involving mostly women. One of the most characteristic lipedema symptoms is painful accumulation of adipose tissue in lower and upper extremities leading to disproportion. Due to the disproportionate body shape, it is recently thought that BMI (Body Mass Index) might not be fully sufficient to identify the weight ratios among lipedema patients and it is suggested to consider replacing BMI with WHtR (Waist-to-height ratio). PURPOSE: The aim of the study is to present the characteristic features of lipedema patients and the usefulness of BMI and WHtR among lipedema patients in reference to symptoms severity, quality of life and body composition. METHODS: Forty-four women with lipedema were asked to rate their symptoms in a scale from 0 to 10, and to complete SF-36 questionnaire affecting quality of life. Participants also had body composition assessment. RESULTS: Participants experienced various lipedema symptoms such as: heaviness in affected areas (97.7%), pain at palpation (100%), spontaneous pain (82%), disproportionate body shape and tendency to bruising (88.6%). The level of pain was strictly correlated with patients' daily functioning (R = 0.79, p = 1.9*10- 10). The quality of life among participants measured with SF-36 was 57.4/100. WHtR enabled the same group of patients to be divided into three nearly equal groups, while BMI only divided them into two groups. Statistically significant differences could be observed both between BMI and WHtR groups. CONCLUSION: Lipedema symptoms have a direct impact on functioning of patients. Quality of life is decreased among women with lipedema. WHtR should be considered as a tool in identification of obesity among lipedema population.

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.

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.