A Cross-Sectional Exploratory Study of Endothelial Biomarkers in Non-Obese Women with and Without Polyendocrine...

Endothelial dysfunction has been reported in polyendocrine metabolic ovarian syndrome (PMOS) and is associated with obesity. We hypothesised that circulating biomarkers of endothelial dysfunction would not differ between non-obese women with PMOS and age- and BMI-matched controls in the absence of major between-group differences in insulin resistance (IR), systemic inflammation or vitamin D status. Plasma concentrations of 20 endothelial-associated proteins were measured using Slow Off-rate Modified Aptamer (SOMAscan) technology in 29 non-obese women with PMOS and 29 age- and BMI-matched controls. Women with PMOS had higher Ferriman-Gallwey scores, free androgen index (FAI) and anti-Müllerian hormone (AMH), whereas HOMA-IR, C-reactive protein (CRP), vitamin D metabolites and endothelial-associated biomarkers did not differ significantly between groups. Within the PMOS cohort, FAI was strongly positively associated with E-selectin (Pearson r = 0.718, p < 0.001, FDR-adjusted q = 0.027), and HOMA-IR was positively associated with ICAM-2 (r = 0.670, p = 0.001, q = 0.046). The FAI-E-selectin association remained robust in Spearman sensitivity analysis (ρ = 0.720, p < 0.001, q = 0.009), whereas the HOMA-IR-ICAM-2 association remained nominally significant (ρ = 0.579, p = 0.007) but not after FDR correction. A positive association between 24,25(OH)₂D₃ and tumour necrosis factor (TNF) was observed using Pearson correlation (r = 0.648, p = 0.002, q = 0.042), but was not retained after FDR correction in Spearman sensitivity analysis. Thus, non-obese women with PMOS did not demonstrate a generalised alteration in circulating endothelial biomarkers compared with matched controls. Hyperandrogenism, in particular, was robustly associated with endothelial activation, whereas associations with IR were less consistent and vitamin D metabolites showed no robust relationship with the endothelial biomarker profile. Collectively, the findings suggest that variation in endothelial activation in non-obese PMOS is more closely associated with metabolic dysfunction and androgen excess than with circulating vitamin D status, while the cross-sectional design precludes inference regarding causality.