Exploratory Association of 12S-HETE with Postprandial Hyperinsulinemia Rather than HOMA-IR in Women with PCOS/PMOS

Polyendocrine Metabolic Ovarian Syndrome (PMOS) is one of the most commonly diagnosed endocrine disorders among women of reproductive age. The proposed term more accurately reflects the pathophysiology of the condition, emphasizing its multisystem nature rather than restricting it to ovarian dysfunction. Polycystic ovary syndrome (PCOS) is estimated to affect approximately 6–20% of women of reproductive age. The condition is characterized by considerable clinical heterogeneity, including menstrual irregularities, hyperandrogenism, difficulties conceiving, and abdominal obesity. In addition to hormonal disturbances, an important and often underestimated aspect of PMOS is its association with insulin resistance and chronic low-grade inflammation. Current evidence indicates that insulin resistance represents an important component of the pathogenesis of PMOS. In this context, the identification of biomarkers reflecting metabolic and inflammatory disturbances in affected women is of particular interest. Pro-inflammatory lipid mediators, such as hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs), are products of fatty acid oxidation and act as active modulators of the inflammatory response. Increased concentrations of these metabolites have been reported in individuals with type 2 diabetes, excessive body weight, cardiovascular diseases, and in women with PMOS. The study included 45 women diagnosed with PMOS, who were divided into groups according to the presence of insulin resistance assessed using the HOMA-IR index. Venous blood plasma was used as the biological material, and the concentrations of selected HETE and HODE metabolites were determined using high-performance liquid chromatography (HPLC). The obtained data were subjected to statistical analysis to assess the associations between lipid mediator concentrations, parameters of carbohydrate metabolism, and selected metabolic indices. Statistical analysis revealed no significant differences in the concentrations of the analyzed oxylipins (HETE and HODE) between patient groups stratified according to HOMA-IR. No significant direct correlations were observed between most of the analyzed metabolites and body mass index (BMI) or fasting blood glucose levels. However, a nominally significant association was identified for 12S-HETE (p = 0.0258), which did not remain significant after Bonferroni correction (adjusted p = 0.1806). Its concentration was nearly twofold higher in patients with PMOS who exhibited postprandial hyperinsulinemia, assessed two hours after an oral glucose tolerance test (OGTT), compared with women who had a normal insulin response. Among the seven oxylipin metabolites analyzed, only 12S-HETE showed a nominal association with postprandial hyperinsulinemia. At the same time, the findings suggest that HOMA-IR and glycemic parameters may not fully reflect changes in the oxylipin profile in patients during the early stages of metabolic dysfunction. The concentrations of several analyzed oxylipins were strongly correlated, whereas 16RS-HETE showed only weak correlations with the other metabolites. Further studies are needed to clarify the relationship between oxylipin concentrations and metabolic dysfunction in women with PCOS/PMOS.