Metabolic and Hormonal Profile of Insulin-Like Peptide 5 (INSL5) in Polycystic Ovary Syndrome: A Prospective Analysis

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with diverse metabolic and hormonal manifestations. Insulin-like peptide 5 (INSL5), a gut-derived hormone of the relaxin/insulin family, is expressed in the central nervous system, colonic and reproductive tissues, but its clinical significance in PCOS remains unclear. This study aimed to evaluate circulating INSL5 levels in PCOS and explore their associations with key hormonal and metabolic parameters. In this prospective cross-sectional study, 45 women with newly diagnosed PCOS and 35 age-matched healthy controls (18-35 years) were evaluated. Clinical characteristics, hormonal profiles, and metabolic markers - including serum anti-Müllerian hormone (AMH) and INSL5 - were assessed. INSL5 levels were measured using enzyme-linked immunosorbent assay (ELISA). Median serum INSL5 levels did not differ significantly between PCOS and control groups (12.5 vs. 15.5 ng/ml; p=0.103). However, within the PCOS group, INSL5 was inversely correlated with body mass index, insulin, HOMA-IR, total and LDL cholesterol, triglycerides, fat mass, and free androgen index, and positively correlated with sex hormone-binding globulin (p<0.05 for all). AMH was significantly higher in the PCOS group and demonstrated a diagnostic cut-off of 5.04 ng/ml (AUC: 0.808; sensitivity: 75.6%; specificity: 74.3%). Although INSL5 did not show diagnostic utility for PCOS, its consistent associations with insulin resistance, androgenic activity, and lipid metabolism suggest a potential role in metabolic regulation. These findings support its relevance as a candidate marker for metabolic phenotyping and warrant further investigation into its physiological role within the PCOS spectrum.