Leuprorelin Acetate for Spinal and Bulbar Muscular Atrophy: A Systematic Review of Clinical Efficacy, Long‐Term Outcomes, and Safety Considerations

Spinal and bulbar muscular atrophy (SBMA; Kennedy disease) is a rare X-linked neuromuscular disorder caused by a CAG repeat expansion in the androgen receptor gene. Leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, suppresses androgen signaling and is approved for SBMA-associated dysphagia in Japan; however, evidence regarding efficacy remains heterogeneous. PubMed and Embase were searched from inception through June 18, 2026, for studies evaluating leuprorelin in genetically confirmed SBMA. Randomized trials, observational cohorts, natural history-controlled studies, extension studies, and safety case reports were included, and findings were synthesized narratively because of substantial heterogeneity. Eleven studies met inclusion criteria, including eight efficacy studies (460 patients) and three safety-focused case reports. Leuprorelin reduced pathogenic androgen receptor accumulation and improved biochemical markers, including serum creatine kinase and creatinine decline. Although neither pivotal randomized trial demonstrated significant short-term functional improvement at 48 weeks, longer-term studies showed slower decline in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Limb Norris, and Norris Bulbar scores and improved event-free survival from pneumonia and death. Benefits were greatest with earlier treatment, particularly disease duration < 10 years. Leuprorelin was generally well tolerated; common adverse effects included hot flushes, sexual dysfunction, and decreased bone mineral density. Leuprorelin may slow long-term functional deterioration in SBMA, with greater benefit following early initiation and prolonged treatment.