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  • 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: 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 characterized by disproportionate gluteofemoral adiposity, often regarded as a metabolic sink, yet its relationship with systemic autoimmunity, specifically celiac disease (CD), remains unexplored. Objective: We investigated the immunometabolic profiles and body composition patterns distinguishing lipedema phenotypes from celiac disease autoimmunity. Methods: This cross-sectional analysis included 3,833 women from NHANES 2011–2014. Celiac disease was defined by strict serology (tTG-IgA+ and EMA-IgA+), while the lipedema phenotype was defined as a leg-to-trunk fat ratio >90th percentile via dual-energy X-ray absorptiometry (DXA). We assessed gynoid fat mass, HOMA-IR, and neutrophil-to-lymphocyte ratio (NLR) compared to controls. Results: CD prevalence was 0.56% (n=11). Women with CD exhibited significantly lower gynoid region percent fat compared to non-celiacs (39.5% vs. 42.6%, p=0.0007). Conversely, the lipedema phenotype was associated with a distinct anti-inflammatory and insulin-sensitive profile, characterized by 44.2% lower HOMA-IR (p<0.001) and 7.6% lower NLR (p=0.012) compared to controls. While broad lipedema criteria did not reach statistical significance for CD exclusion due to low case numbers (p=0.570), no celiac cases were observed in the highest tier of gynoid adiposity. Conclusions: Although prevalence differences did not reach statistical significance, this study of US women demonstrates a phenotypic divergence where celiac disease is associated with reduced gynoid adiposity, contrasting with the superior immunometabolic profile observed in the lipedema phenotype. These findings suggest that these conditions represent opposing physiological states regarding gynoid adipose tissue function.

Last update from database: 1/27/26, 9:11 AM (UTC)

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