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Knee pain in women with lipedema is frequently misattributed and undertreated. We outline a biomechanical and inflammatory cascade linking systemic adipose dysfunction, anabolic resistance, and thigh-predominant sarcopenia to dynamic knee valgus, plantar arch collapse, altered gait, patellofemoral malalignment, and ultimately chondromalacia patellae. We integrate synovial-adipose crosstalk and the high prevalence of generalized joint hypermobility as amplifiers of joint loading. This framework supports a practical, staged approach that couples symptom control with progressive, targeted strengthening and gait retraining. Rather than treating the knee in isolation, addressing the cascade may reduce pain and improve function.

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.

Background Lipedema is a chronic adipose tissue disorder affecting primarily women and is increasingly associated with immune dysregulation and intestinal permeability. Food-specific IgG testing has been explored in various inflammatory conditions, but its relevance to lipedema remains unknown. Objective The objective of this study is to characterize IgG food sensitivity profiles in women with lipedema and investigate the paradoxical relationship between increased food reactivity and reduced total IgG antibody levels. Methods We conducted a retrospective cross-sectional study involving 234 participants: women with lipedema (n=80), women without lipedema (n=74), and men (n=80). All had undergone IgG testing against 222 food antigens via ELISA. We analyzed qualitative (positive/negative) and quantitative IgG reactivity, applied dimensionality reduction (PCA, t-SNE) and clustering, and developed a multivariable logistic regression model to assess diagnostic performance. Results Women with lipedema exhibited a non-significantly higher number of positive IgG food reactions (14.8 vs 12.6; p=0.186), despite significantly lower total IgG levels (1747.1 vs 2974.8 AU; p<0.001). This paradox was consistent across 79.7% of tested antigens. The most discriminative foods included wild game meats and certain vegetables. A combined IgG-based model achieved an area under the curve of 0.804, outperforming individual IgG metrics. Dimensionality reduction revealed no clear clustering based on reactivity patterns alone. Conclusion Lipedema displays a paradoxical IgG signature, more frequent positives despite lower total IgG, consistent with mucosal immune dysregulation (e.g., increased intestinal permeability, immune exhaustion, or dietary monotony). Single IgG metrics had limited discrimination, but a combined score improved classification, supporting IgG profiling as a complementary, not standalone, biomarker for patient stratification and personalized dietary guidance. Collectively, these findings suggest that the adipose phenotype may be downstream of broader systemic processes; prospective studies should assess IgG subclasses, barrier markers (e.g., zonulin), and gluten-modulated interventions.

Lipedema is a chronic adipose tissue disorder traditionally considered to affect almost exclusively women, with recent estimates suggesting approximately 0.2% prevalence in men worldwide; the condition remains underdiagnosed in males due to limited awareness and scarce literature. This retrospective case series from the Amato Institute of Advanced Medicine in São Paulo, Brazil, describes clinical characteristics, diagnostic findings, and treatment outcomes of five male patients diagnosed with lipedema between January 2022 and December 2024. The patients, aged 31-58 years (mean, 42.6 ± 9.7), with a BMI of 29-42.4 kg/m², all presented bilateral, symmetrical lower extremity fat accumulation, sparing the feet, with endocrine comorbidities present in 80% of cases and one participant testing positive for HLA-DQ2/DQ8. Diagnosis was based on clinical criteria requiring bilateral symmetrical fat accumulation, disproportionate fat distribution, negative Stemmer’s sign, sparing of feet, and at least two minor criteria. Conservative management, including dietary interventions over four to eight weeks, resulted in mean weight reduction of 7.0 ± 2.2 kg and lower limb volume reduction of 2.5 ± 1.1 L. These findings demonstrate that lipedema occurs in men with classical phenotypic features, and the presence of HLA-DQ2/DQ8 markers in some cases suggests potential autoimmune components and opportunities for targeted dietary interventions. Conservative management yields significant short-term improvements, warranting larger prospective studies to establish prevalence, investigate HLA associations, and optimize management strategies for male lipedema.