P342 - ECE_2334 - Pro-inflammatory cytokine profiling in polycystic ovary syndrome phenotypes: excess abdominal adiposity vs hyperandrogenism
TL;DR
Healthy and high WHtR groups had similar age, IL-1β, IL-8, TNFα, testosterone, DHEAS, FIB-4 and diastolic BP (DBP).
Abstract
Polycystic Ovary Syndrome (PCOS) is increasingly recognised as a systemic illness extending beyond the scope of the reproductive disorder. Chronic low-grade inflammation is a key driver in the development and progression of cardiovascular disease (CVD) and inflammation has been reported in both PCOS and in those with excess abdominal adiposity. We assessed inflammation in PCOS phenotypes based on either excess abdominal adiposity or hyperandrogenism. PCOS women were classified into four groups based on central adiposity (healthy/waist to height ratio (WHtR) 0.40-0.49 vs high/WHtR ≥0.6) and biochemical androgen status (normal/free androgen index (FAI) <5.0 vs hyperandrogenism/FAI>5.0. Groups were compared for cytokines (interleukins (IL-6, IL-1β, IL-8) and tumour necrosis factor α (TNFα)), BMI, HOMA-IR, blood pressure (BP), fibrosis-4-index (FIB-4), testosterone, DHEAS and FAI. Python (v3.14) was used for statistical analysis. P < 0.05 was considered statistically significant. Data is reported as median (IQR). The number of women in each sub-group were as follows: 15 with healthy WHtR, 23 with high WHtR, 32 with FAI ≤5.0 and 19 with FAI >5.0. Healthy and high WHtR groups had similar age, IL-1β, IL-8, TNFα, testosterone, DHEAS, FIB-4 and diastolic BP (DBP). High WHtR had higher % of non-White ethnicities 31 vs 8%, BMI 41.7(34.3-45.3) 23.6(21.7-24.5) kg/m2 (P < .0001), IL-6 4.48(2.88-7.90) vs 1.61(1.21-1.98) ng/L (0.02), IL-6/TNFα 0.37(0.32-0.49) vs 0.16(0.113-0.20) (0.01), HOMA-IR 4.19(2.88-10.32) vs 1.16 (0.68-2.08) (0.02), FAI 5.25(2.08-6.50) vs 2.70 (2.20-3.40) (0.04) and systolic BP (SBP) 124(113-134) vs 108(116-118) mmHg (0.004). FAI ≤5.0 and >5.0 groups had similar age, % ethnicity, WHtR, cytokines, FIB-4, SBP and DBP. Those with FAI >5.0 had higher BMI 39.4(30.9-45.5) vs 27.9(23.7-34.9) kg/m2 (0.02), testosterone 1.6(1.5-2.4) vs 1.3 (0.9-1.5) nmol/L (<0.0001), DHEAS 6.4(4.5-7.4) vs 2.3(1.9-3.3) umol/L (<0.0001) and HOMA-IR 3.15(2.56-5.04) vs 2.07(1.14-3.32) (0.04). There were no significant correlations between WHtR or FAI with any of the cytokines. However, numerous women exhibited circulating pro-inflammatory cytokines above the upper limits of normal, with elevated IL-6 in 64%, IL-8 and IL-1β in 48%, and TNFα in 28%. There was no difference in WHtR, FAI or IL-6 between White and non-White ethnicities. In our cohort, excess abdominal adiposity was a stronger driver of IL-6, HOMA-IR and SBP with androgen excess driving primarily HOMA-IR. PCOS is associated with a heightened inflammatory burden, independent of BMI/androgen excess. These findings may suggest a role for active CVD risk stratification and prevention measures across all PCOS phenotypes.