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

Context: 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.

Objective: To determine whether PCOS exhibits a profile of chronic inflammation or immune dysregulation when analyzed across a diverse patient population.

Design: Retrospective cross-sectional study of samples collected between 1987 and 2010 as part of the Androgen Excess Biorepository.

Setting: 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.

Patients: 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.

Main outcome measures: 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.

Results: 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.

Conclusions: 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.