Distinct metabolomic profiles in lean and non-lean polyendocrine metabolic ovarian syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS)/polyendocrine metabolic ovarian syndrome (PMOS) is the most prevalent endocrine disorder in reproductive-age women and is characterized by long-term metabolic consequences. The purpose of this study is to delineate the metabolomic profile in lean and non-lean PMOS patients. METHODS: Retrospective cross-sectional study includes 4768 premenopausal patients with available body mass index (BMI) and metabolomics information at the Mass General Brigham (MGB) Biobank. The Biobank includes samples collected from 05/2010 to 08/2023 with unique metabolomic biomarkers that encompass key metabolic pathways, including lipids, amino acids, and glycolysis-related metabolites. The main outcome measures were metabolomic profile differences between PMOS (n = 403) and non-PMOS patients (n = 4365). Sub-analyses were performed within normal BMI (< 25 kg/m2), overweight BMI (25-29.9 kg/m2), and obesity BMI (≥ 30 kg/m2) subgroups. RESULTS: PMOS patients were younger (p < 0.001) and had higher BMI (p < 0.001). When considering the total population and adjusting for age, BMI, exercise, metformin, oral contraceptive pills (OCPs), and glucagon like peptide-1 (GLP-1) agonists, PMOS affected the expression of only 1/71 (1.4%) parameter compared to the non-PMOS group. In the normal BMI sub-group, there were no differences in any of the metabolomic parameters when controlling for age, exercise, metformin, OCPs, and GLP-1 agonists except for creatinine levels that were lower in PCOS. In the overweight BMI sub-group, when adjusting for the same confounders, PMOS diagnosis had an impact on 4/71 (5.6%) of the metabolomic parameters, mostly in the family of amino acids. Lastly, in the obesity BMI subgroup, adjusted analysis showed no association between PMOS and any of the metabolites under evaluation. CONCLUSION: Metabolomic signatures of PMOS differ by BMI phenotype. Minimal disturbances were noted in lean PMOS patients. In contrast, PMOS patients with overweight BMI demonstrate broader metabolomic differences and subsequent implications.