GLP-1 Receptor Agonists in Preconception Management of Obese Women with Polyendocrine Metabolic Ovarian Syndrome (PMOS): Metabolic and Reproductive Implications

Objective: To evaluate the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on metabolic parameters, hormonal profiles, and reproductive outcomes in the preconception management of women with polyendocrine metabolic ovarian syndrome (PMOS) and obesity.Methods: A comprehensive literature search was conducted across scientific databases, including PubMed/MEDLINE, Scopus, and Web of Science, focusing on clinical trials, reviews, and guidelines published between January 2022 and April 2026. Studies evaluating the efficacy, safety, tolerability, and economics aspects of GLP-1 RAs used alone or combined with metformin in obese PMOS phenotypes were systematically analyzed.Results: GLP-1 RAs demonstrate favorable clinical efficacy compared to conventional lifestyle modifications and metformin in reducing body weight and visceral adiposity. By addressing the adipose-androgen crosstalk and mitigating low-grade chronic inflammation, GLP-1 RAs improve insulin sensitivity and reduce compensatory hyperinsulinemia. This metabolic optimization promotes increased hepatic sex hormone-binding globulin (SHBG) synthesis and decreased circulating free testosterone levels, facilitating the restoration of regular menstrual cycles and spontaneous ovulation. Combination therapy of GLP-1 RAs with metformin yields robust synergistic effects, though consideration of higher treatment costs is warranted. Due to limited definitive data on fetal safety during early pregnancy exposure, a strict pre-pregnancy washout period remains mandatory.Conclusion: GLP-1 RAs offer a promising, multisystemic therapeutic strategy for the preconception management of PMOS with obesity, effectively breaking the cycle of insulin resistance and hyperandrogenemia. While providing profound metabolic and reproductive benefits, strict adherence to preconception discontinuation protocols is essential. Future large-scale randomized controlled trials are required to further clarify optimal dosing, long-term safety, and definitive gestational outcomes.