Lack of Scientific Evidence for the Use of Gestrinone in the Treatment of Lipedema: A Systematic Review

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.