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Objective: The aim of this study was to identify the demographic and clinical characteristics of patients with lipedema who presented to our outpatient clinic in Çorum, thereby contributing to defining the lipedema case profile in our country. Material and Methods: We included 80 female patients diagnosed with lipedema at the physical medicine and rehabilitation outpatient clinic of our hospital between January 2020-July 2023. Data on age, body mass index (BMI), lipedema type-stage, and symptoms were collected from medical records. Laboratory evaluations, including hemogram, 25-OH vitamin D, vitamin B12, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lower limb venous doppler ultrasound results were also obtained from medical records. Results: The mean age was 46.46±9.72 years and BMI was 32.12±4.84. Type 2 lipedema was the most common, followed by Type 1 and Type 3. Stage 2 lipedema was seen in 63.8% of the patients, stage 1 in 21.2%, and stage 3 in 15%. Common symptoms included pain, swelling, fatigue, and leg heaviness. The mean CRP was 4.88±2.89 mg/L, ESR was 18.58±10.06 mm/h, 25-OH vitamin D was 18.73±12.95 ng/dl, and vitamin B12 was 359.74±155.12 pg/ml. Venous insufficiency was present in 50% of the patients. Lipedema stage showed significant positive correlations with age (r: 0.284, p: 0.011), BMI (r: 0.307, p: 0.006), and ESR (r: 0.271, p: 0.015).Conclusion: Patients presenting with swelling and pain in the lower limbs should always be assessed for lipedema, and it should also be considered that venous insufficiency and vitamin deficiencies may coexist in these patients.

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BACKGROUND: Women with lipedema have an abnormal accumulation of adipose tissue that leads to pain and reduced quality of life (QoL). The impact of lipedema on body image and QoL remains largely unknown. The aim of this study is to explore Health-Related QoL (HR-QoL) and body image in women with lipedema and compare it to healthy women without lipedema as well as women with advanced cancer. METHODS: This comparative study included women with lipedema (n = 104), healthy women without lipedema (healthy controls) (n = 42), and an exploratory group of women with advanced cancer (n = 44). HR-QoL was assessed using RAND-36, body image concern was evaluated with the Body Shape Questionnaire (BSQ), and symptoms were assessed with Edmonton Symptom Assessment System (ESAS). RESULTS: In total, 190 women were included. Women with lipedema had significantly lower HR-QoL compared to healthy women without lipedema across all eight dimensions (p < 0.001). Women with lipedema had HR-QoL scores comparable to those of women with advanced cancer in four dimensions: physical functioning, bodily pain, and emotional problems. In the general health dimension, women with lipedema had even lower scores than women with advanced cancer (p < 0.05). Body image concerns were significantly greater in the lipedema group than in healthy controls (p = 0.001). Women with lipedema experienced significantly more symptoms than healthy controls, including more pain, fatigue, depression, anxiety, loss of appetite, dyspnea and reduced QoL (<0.001 for all). CONCLUSION: Women with lipedema had as low HR-QoL as women with advanced cancer in several dimensions, significant body image concerns and high symptom burden. These findings underscore the need to develop targeted health care initiatives for these patients.

BACKGROUND: Lipedema is a chronic adipose tissue disorder with disproportionate fat accumulation in the extremities and is often misdiagnosed as obesity. Although women with lipedema appear to be metabolically distinct from body mass index (BMI)-matched controls, their fasting metabolism remains insufficiently characterized. We therefore aimed to define the metabolic signature of lipedema using serum NMR metabolomics and anthropometric profiling. METHODS: We conducted a study with 24 premenopausal women with lipedema and 21 BMI-matched controls. Fasting serum samples were analyzed using NMR spectroscopy and anthropometric data were collected. Regional body composition was additionally assessed in an exploratory matched DXA subset (n=12). To characterize coordinated metabolic differences beyond single analytes, we derived exploratory composite indices and applied multivariate analyses. RESULTS: Despite similar BMI, women with lipedema showed lower waist circumference, waist-to-hip ratio and lower fasting insulin than controls (age-adjusted p = 0.032). NMR profiling revealed lower alanine (p < 0.001), lactate (p = 0.004), pyruvate (p = 0.021), and elevated ketone bodies (3-hydroxybutyric acid: p = 0.009; acetoacetic acid: p = 0.035; acetone: p = 0.006). These alterations were reflected by significant group differences in composite indices for fat distribution (g = 1.26; p < 0.001), glycolysis (g = 0.74; p = 0.018), and ketone metabolism (g = 0.70; p = 0.018). Principal component analysis of the selected indices explained 78% of the total variance and showed partial group separation between lipedema and controls. CONCLUSION: Lipedema is associated with a distinct fasting metabolic profile characterized by reduced glycolytic intermediates, enhanced ketone body signals, and a more peripheral fat distribution despite comparable BMI. These findings support the concept of lipedema as a metabolically distinct phenotype and suggest that multivariate metabolic signatures may help refine future diagnostic and interventional approaches.

Lipedema is a chronic disorder of adipose tissue characterized by symmetrical, dispro portionate enlargement of subcutaneous adipose tissue, most commonly affecting the lower extremities, and accompanied by pain, heaviness, and easy bruising. Its pathophysiology involves alterations in adipocytes, microcirculation, extracellular matrix, inflammatory activity, and, in some patients, fluid retention or lymphatic insufficiency. Weight reduction may be beneficial, particularly in patients with con comitant overweight or obesity, but it does not provide causal treatment and its effects are variable. Nutritional therapy is a supportive component of comprehensive management, aimed at symptom relief, potential metabolic risk, functional status, and quality of life. The approach should be individualized, sustainable, and ideally guided by a qualified nutrition therapist. Care should also include lifestyle measures, physical activity, compression therapy, patient education, appropriate communication, and consideration of psychological aspects.

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

Lipedema is a chronic, female-predominant disorder of subcutaneous adipose tissue characterized by disproportionate fat expansion, pain, and fibrosis. Despite its high prevalence, the cellular mechanisms underlying lipedema remain poorly understood. While the clinical features have been extensively described, its biology of adipose tissue dysfunction and aberrant intercellular communication is still unclear. In comparison to obesity, lipedema is marked by local dysregulation of adipocyte-stromal and adipocyte-vascular interactions. In this hypothesis perspective, we discuss emerging mechanistic concepts from a cell biology perspective that are particularly relevant to lipedema, focusing on (i) organelle contact site dynamics in adipocytes and their role in lipid handling and stress adaptation; (ii) extracellular vesicle (EV)-mediated crosstalk between endothelial cells, adipocytes, and immune cells as a driver of localized inflammation and fibrosis; and (iii) estrogen-linked signaling pathways that may imprint EV cargo and cellular behavior in a sex-specific manner. By integrating these perspectives, we highlight open experimental settings and mechanistic parallels to other adipose tissue pathologies that help understanding lipedema as a distinct cellular and molecular entity. Investigating how organelle biology, extracellular vesicles communication and hormonal context intersect in adipose tissue may uncover novel biomarkers and therapeutic entry points for this long-neglected condition.

Adipose tissue derived stromal vascular fraction (SVF) has emerged as cell therapeutic applicable by point-of-care one-step procedures in autologous settings. Even a mechanical isolation, completed within minutes, is typically followed by multiple steps such as cell washing, filtration, erythrocyte lysis and cryopreservation, which may impact the cell isolate in terms of cell amounts and quality. Using the BioMicroMill, a straightforward device providing mechanically isolated SVF suited for multiple therapeutic doses, we aimed to evaluate the impact of relevant processing steps during isolation and cryopreservation on cell quantity and quality in terms of viability, the presence of regenerative cells, pro-regenerative secretome, vascular network formation. The mechanical isolation yielded in the mean 3.4 × 105 ± 1.42 × 105 SVF cells per ml of lipoaspirate with a mean viability of 38% ± 7.2%. It comprised a heterogeneous mixture of single cells, cell aggregates, extracellular matrix, and microvascular fragments enriched from adipose tissue, providing functionally relevant cell populations (CD31, CD34, CD90, CD105). Adipose-derived stromal cells (ASC) exhibited robust outgrowth, proliferation, and differentiation capacity in vitro. The SVF showed pronounced paracrine activity (IL-10, VEGF-A, HGF, IL-6, IL-8, MCP-1), including proangiogenic factors, and supported 3D vascular network formation, demonstrating strong proangiogenic potential. However, all additional SVF processing steps substantially influenced total cell yield, with cumulative cell losses (erylysis 68% ± 16%, filtration 67% ± 16%, washing 54% ± 9%) but no loss of viability or ASC attachment and proliferation in vitro was observed. In contrast to other processing steps, filtration substantially altered SVF composition towards single cells, which was also reflected in an altered paracrine activity (significant increase in IL-10 and reduction to minimal levels of HGF). Furthermore, despite further cell loss (mean 47% ± 16%), cryopreservation maintained functional cell populations including ASC, paracrine activity and support of 3D network formation in vitro. Taken together, our data demonstrate that processing steps can influence both cell yield and quality. Accordingly, protocol selection should be guided by the intended application and the required functional properties and therefore warrants careful consideration.

Review Article Background: Lipedema and advanced lymphedema are chronic disorders of adipose and lymphatic tissues that remain frequently underdiagnosed. Their coexistence poses therapeutic challenges, particularly when conservative management fails. Although international guidelines support surgical intervention in selected cases, real-world data from resourcelimited hospital settings remain scarce. Objective: To report the experience of a Moroccan tertiary university hospital in the surgical management of advanced lipedema and lymphedema and to compare clinical outcomes with current international recommendations. Methods: A retrospective descriptive case series was conducted between 2021 and 2024. Three patients underwent surgical treatment using tumescent liposuction or en bloc tissue resection with skin grafting. Postoperative outcomes were assessed clinically and through a structured quality-of-life questionnaire inspired by the SF-36, focusing on pain, mobility, and overall satisfaction. Results: All procedures were completed without intraoperative or postoperative complications. The volume of aspirated adipose tissue ranged from 2.1 to 4.0 L. One patient with advanced secondary lymphedema required surgical resection, with evacuation of 1.2 L of lymphorrhea. Postoperative satisfaction ranged from moderate to high, with reported quality-of-life scores between 5 and 8 out of 10. These findings are consistent with outcomes reported in recent international series. Conclusion: Surgical treatment of advanced lipedema and lymphedema is feasible, safe, and clinically beneficial, even in resource-limited settings. An individualized, guideline-based approach allows satisfactory functional and quality-of-life outcomes. Further prospective studies with standardized assessment tools are required.

Lipedema is a chronic adipose tissue disorder characterised by disproportionate accumulation of subcutaneous fat within specific anatomical depots, most commonly the lower extremities, with relative sparing of the trunk. Despite increasing clinical recognition, the mechanisms underlying the selective vulnerability of particular adipose depots and the progressive tissue remodelling observed in lipedema remain poorly understood. Emerging evidence suggests that lipedema is associated with complex alterations in adipocyte biology, adipose stem and progenitor cell (ASPC) function, immune signalling, vascular integrity, extracellular matrix remodelling, and lymphatic homeostasis, indicating that the disease extends beyond simple fat accumulation. Recent advances in adipose tissue biology have demonstrated that adipose depots are not functionally uniform structures, but rather anatomically distinct cellular ecosystems with unique developmental origins, transcriptional programs, stromal composition, immune niches, and metabolic properties. These depot-specific characteristics may provide an important framework for understanding the regional distribution and progression of lipedema. However, while substantial progress has been made in defining differences between visceral and subcutaneous adipose tissue, heterogeneity between individual subcutaneous depots remains comparatively underexplored despite its likely relevance to disorders of regional adipose expansion. The emergence of single-cell and spatial transcriptomic technologies has transformed the study of adipose tissue by enabling high-resolution mapping of adipocytes, stromal populations, vascular cells, and immune microenvironments within healthy and diseased tissue. These approaches offer an unprecedented opportunity to investigate depot-specific cellular states, intercellular signalling networks, and spatial tissue architecture in lipedema. In this review, we synthesise current evidence regarding tissue remodelling and adipose depot heterogeneity in lipedema and examine how single-cell and spatial omics approaches may advance mechanistic understanding of disease pathophysiology. We further discuss current technical and conceptual limitations within the field and highlight future directions for developing integrated adipose tissue atlases capable of identifying disease-driving cellular programs and therapeutic targets in lipedema.

Lipedema in its various clinical stages is a condition that almost exclusively affects the female sex and appears at puberty. The oedema does not respond to common low-calorie diets, nor to exercise, nor to common anti-oedema medical therapies, nor to bariatric surgery. In the more advanced clinical stages, it can induce more or less important functional impairments that induce physical disability, as well as psychological, relational, and social discomfort: pain, functional walking impotence, easy muscular fatigability, sleep-wake rhythm disturbances also linked to the state of anxiety and depression that affects subjects in whom, often, the response to the treatments they are directed towards is practically nil. Many epidemiological, aetiopathogenetic, diagnostic, and clinical aspects still need to be studied in depth, considering, moreover, that the disease was only recognized with its own specific code by the World Health Organization in the 11th edition of the International Classification of Diseases on 1 January 2022.

Introduction  Lipedema is a chronic disease characterized by symmetrical and painful accumulation of subcutaneous fat, influenced by genetic and hormonal factors, and frequently misdiagnosed as obesity or lymphedema. Materials and Methods  In the present narrative review, we searched the PubMed and SciELO databases for articles published between 2015 and 2025, in Portuguese and English, addressing the diagnosis and the clinical or surgical management of lipedema. Results  In the PubMed search, we identified 299 studies, which were reduced to 106 after the removal of duplicates, with a progressive increase in publications since 2020; in the search on SciELO, we only retrieved 7 studies, all of which were also indexed in PubMed. The results reinforce that lipedema presents a complex pathophysiology, involving adipocyte hypertrophy and hyperplasia, chronic inflammation, microvascular dysfunction, and estrogen-related influence. International consensus indicates that diagnosis is essentially clinical, and that conservative treatment should be prioritized, including weight management, nutritional guidance, low-impact exercise, compression therapies, and psychosocial support. Surgical intervention, particularly tumescent or water-assisted liposuction techniques, is reserved for refractory cases and does not constitute a definitive cure. The growing alignment among consensus statements published over the past 5 years highlights the need for standardized diagnostic criteria and therapeutic protocols. Conclusion  The effective management of lipedema requires a multidisciplinary approach, continuous professional education, and strengthening of research that enable the establishment of evidence-based clinical guidelines. Keywordsdiagnosis; lipedema; literature review; surgery; treatment

Lipedema is a chronic and often debilitating adipose tissue disorder that primarily affects women. The disease is characterized by disproportionate and symmetrical accumulation of subcutaneous fat in the extremities. Despite the high prevalence of lipedema, which affects ∼10% of women, and its significant impact on patient quality of life, lipedema is understudied and often misdiagnosed as other disorders (obesity or lymphedema). In this review, we explore the current understanding of lipedema through clinical, tissue, and cellular lenses, and examine suspected pathological mechanisms, including hormonal influences (such as estrogen), adipocyte hypertrophy and hyperplasia, increased extracellular matrix (ECM) fibrosis, and specialized immune cell involvement, including M2 macrophage infiltration. Recent advancements in adipose tissue engineering, including organoids, fat-on-a-chip platforms, and the use of induced pluripotent stem cells (iPSCs) are explored as platforms to study lipedema pathogenesis.

Lipedema is a chronic disorder characterized by abnormal subcutaneous fat accumulation, mainly in women's lower limbs. The aim of the study was to analyze the safety and efficacy of liposuction in treating lipedema. A systematic review was conducted in PubMed, Scopus, and MEDLINE until June 2024 using the terms "lipedema," "liposuction," "results," and "complications." Twenty-five studies were included (n = 2373 patients). Liposuction, mainly using the tumescent infiltration, reduced pain, BMI, and functional limitations, with improvements in mobility and quality of life. Mean aspirated fat volume was 3077 mL per session and 6111 mL per treatment course. Complications were uncommon (hematomas, edema, anemia, DVT, and rare methemoglobinemia). Moreover, improvements were maintained during the follow-up, suggesting that the beneficial results were sustained over time. Although 15 studies reported using tumescent, only 2 fully described the anesthetic fluid composition. Liposuction is a safe and effective treatment for lipedema, but variability in techniques and postoperative care highlights the need for standardized protocols and further research. Level of Evidence: 4 (Therapeutic).

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 lipoedema patients with obesity but does not consistently improve core lipoedema symptoms. Its role remains adjunctive rather than primary. Larger prospective studies using standardised definitions and outcome measures are needed to clarify its therapeutic value in this population.

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 causes abnormal fat accumulation in the limbs, leading to pain, functional impairment, and body image disturbance. Nowadays, various liposuction techniques are available. The wet technique is increasingly being considered as the gold standard; however, comparative data between the dry and wet methods remain limited. We evaluated the efficacy of liposuction and compared outcomes between dry and wet approaches. Our analysis focused on surgical characteristics, complication rates, and clinical outcomes including pain relief, functional improvement, and esthetic satisfaction, with comparisons made between preoperative and 12-month postoperative results. METHODS: Besides surgical data extraction, patient-reported outcome measures (PROMs) were obtained through three different standardized questionnaires to assess pain relief, function gain, and esthetic satisfaction. RESULTS: Both techniques were effective, demonstrating overall improvements in pain, function, and body image, when comparing pre and postoperative outcomes. Lipoaspirate volumes were comparable between the groups. Operative time was significantly shorter in the wet technique group. Short-term complication rates did not differ between dry and wet techniques. While both techniques led to a global improvement, the wet technique showed greater potential in pain reduction and better esthetics satisfaction 12 months post-surgery. CONCLUSION: Lipedema is a complex disease that is still poorly understood. Liposuction may offer symptomatic relief regardless of the technique used, but the wet technique demonstrates better postoperative results, with improved PROMs and fewer complications. The treatment of lipedema requires a multidisciplinary approach, while conservative therapy remains the first-line option, surgical treatment by wet liposuction should be considered for its significant potential in improving functional outcomes and as an effective therapeutic option.