Metabolic, hormonal, and reproductive effects of GLP-1 receptor agonizts in hyperandrogenic insulin-resistant women: a systematic review

CONTEXT: Hyperandrogenic insulin-resistant states, most commonly polycystic ovary syndrome (PCOS) and severe phenotypes such as HAIR-AN syndrome, are characterized by metabolic dysfunction, androgen excess, and reproductive disturbance. Insulin resistance is a central pathogenic driver and therapeutic target. OBJECTIVE: To systematically evaluate the effects of glucagon-like peptide-1 (GLP-1) receptor agonizts on metabolic, hormonal, and reproductive outcomes in adult women with hyperandrogenic insulin-resistant states. Data Sources and Study Selection: A systematic search identified randomized controlled trials, observational studies, and case series evaluating GLP-1 receptor agonizts in PCOS and HAIR-AN syndrome, reflecting the heterogeneity of the current evidence base.Data extraction and synthesis Outcomes were synthesized across metabolic (anthropometric and glycaemic), hormonal, reproductive, dermatologic, and safety domains, accounting for heterogeneity in interventions and study designs. RESULTS: Metabolic responses appeared more consistent and robust than endocrine outcomes. Reproductive outcomes such as menstrual regularity were variably reported and showed inconsistent improvement across studies, limiting firm conclusions regarding fertility-related benefit. Evidence in severe phenotypes remains limited but suggestive of clinical benefit. CONCLUSIONS: GLP-1 receptor agonizts are a promising adjunctive therapy in hyperandrogenic insulin-resistant states, with the strongest evidence for metabolic improvement. Reproductive and endocrine outcomes remain less consistent, likely reflecting heterogeneity in study design, populations, and outcome reporting. Further high-quality, phenotype-specific trials are required.