Multi-Racial Cytokine Profiling Reveals Immune Dysregulation not Chronic Inflammation in Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder often associated with chronic inflammation, but comprehensive characterization of immune markers across diverse patient populations is lacking. To determine whether PCOS exhibits a profile of chronic inflammation or immune dysregulation when analyzed across a diverse patient population. Retrospective cross-sectional study of samples collected between 1987 and 2010 as part of the Androgen Excess Biorepository. Reproductive endocrinology clinics at the University of Alabama at Birmingham (UAB) in Birmingham, Alabama, and Cedars-Sinai Medical Center (CSMC) in Los Angeles, California, where women and adolescents presented for evaluation of androgen excess. 40 premenopausal women (20 with PCOS, 20 controls) aged 18-45 years, categorized by race (Black and White) and PCOS diagnosis. Participants were race, age, and BMI-matched. Fasted follicular phase plasma concentrations of CRP and 96 circulating immune markers, including IL-6, TNF-α, and IL-18, measured using a Milliplex Luminex xMAP assay. PCOS patients showed significantly lower levels of circulating immune markers (p<0.05). Growth factors (VEGF-A, PDGF), pro-inflammatory cytokines (IL-8, TNF-α, IFN-γ), and several chemokines were reduced in PCOS patients, independent of race. Only IL-18 and CXCL16 showed statistically significant differences between Black and White women. This study challenges the prevailing notion of PCOS as a disorder of chronic low-grade inflammation, suggesting instead that immune suppression and impaired angiogenic signaling may be factors in PCOS pathophysiology, especially in non-obese patients. Further research with larger sample sizes and inclusion of metabolic metrics is needed to confirm these findings before they can be applied in clinical practice.