Gestrinone 2.5mg capsules

Background: Gestrinone is a synthetic hormone derived from 19-nortestosterone, exhibiting androgenic, anabolic, anti-progestogenic, and antiestrogenic effects. Gestrinone subcutaneous implants have been used "off label" for aesthetic purposes due to their anabolic action, promoting accelerated metabolism and muscle gain. Objective: Our goal is to conduct a systematic review focused exclusively on identifying the safety profile of gestrinone use, without addressing efficacy. Methods: This systematic review was performed according to the Joanna Briggs Institute and Cochrane Collaboration recommendations and is reported following the Preferred Reporting Items for Systematic Reviews and Network Meta-Analyses. This article's searches were carried out in the PubMed, Embase, and Web of Science databases. Results: A total of 32 articles were included in this study. The reported adverse events associated with the use of gestrinone were amenorrhea (41.4% of cases), acne, seborrhea (42.7% of reports), decreased libido (26.5%), and hot flushes (24.2%). Other nonspecific symptoms such as hoarseness and cramps were also fairly reported (3.5% and 18.6%, respectively). Other reported effects were associated with breast size reduction (23.7% of patients) and increased transaminases (15.1%). Most studies (40%, n = 24 studies) found significant weight gain (ranging from 0.9 to 8 kg per patient). Abnormalities in bone mineral density were reported in four studies. Conclusions: The evidence remains insufficient to fully understand the risks of gestrinone uses associated with its widespread, unregulated use. Thus, further standardized studies and regulatory oversight to ensure patient safety are needed to mitigate potential health risks.

Abstract licence: CC BY 4.0

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.

Abstract licence: CC BY

Background Pelvic pain secondary to endometriosis is a disabling condition. There are multiple treatments available, with variable endpoints. No prospective controlled studies were carried out evaluating subdermal pellets of gestrinone in this population.Methods One hundred participants with documented deep infiltrative endometriosis who underwent surgery without satisfactory response will be randomly assigned (1:1) to either gestrinone 85 mg subdermal bioabsorbable pellets or placebo. Both arms will receive levonorgestrel-releasing intrauterine system (LNG-IUS 12). The treatment duration will be 6 months, with baseline, 3 months and 6 months clinical visits. The primary endpoint is a combination of serious adverse events (SAEs) accumulated within 6 months of insertion of the gestrinone or placebo pellet and collected through spontaneous reports and clinical findings. They include death, threat or risk to life, need for hospitalization, prolongation of pre-existing hospitalization, permanent disability or damage, congenital anomaly; or significant medical occurrences such as venous thromboembolism. The primary safety outcome will be the percentage of patients who do not experience SAEs 6 months after randomization. Androgenization, changes in laboratory exams and in pelvic pain intensity as well as quality of life (SF-36 and EHP-30 questionnaires) will be further evaluated. Daily data on uterine bleeding patterns and the use of pain relief medication will be remotely collected using an App. Pharmacokinetics profile of gestrinone pellet will be characterized.Conclusion This is the first multicenter randomized controlled trial to evaluate the safety, tolerability and pharmacokinetics profile of subdermal gestrinone pellets and might inform clinical practice for treating these patients.Administrative Information GLADE trial is registered at ClinicalTrials.gov (NCT05570786). This is an investigator-initiated research supported by Biòs Farmacêutica.

Abstract licence: CC BY 4.0