Abstract
OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with metabolic risk. Complement proteins regulate inflammation and lipid clearance but their role in PCOS-associated metabolic risk is unclear. We sought to establish whether the complement system is activated in PCOS in the fasting and postprandial state. DESIGN: Case-control study. PATIENTS: Fasting complement levels were measured in 84 women with PCOS and 95 healthy controls. Complement activation post-oral fat tolerance test (OFTT) was compared in 40 additional subjects (20 PCOS, 20 controls). MEASUREMENTS: Activation pathway (C3, C4, C3a(desArg), factor B, factor H, properdin, Factor D) and terminal pathway (C5, C5a, terminal complement complex [TCC]) proteins were measured by commercial or in-house assays. RESULTS: Fasting C3, C3a(desArg) and TCC concentrations were increased in insulin-resistant (adjusted differences: C3 0.13 g/L [95%CI 0-0.25]; C3a(desArg) 319.2 ng/mL [19.5-619]; TCC 0.66 μg/mL [0.04-1.28]) but not in insulin-sensitive women with PCOS. C3 and factor H levels increased with obesity. Post-OFTT, C3 and C4 levels increased to a similar extent in PCOS subjects and controls, whist factor H levels increased more in women with PCOS compared to controls (adjusted differences (area under the curve): 12 167 μg min/mL [4942-19 392]), particularly in the presence of concomitant obesity. CONCLUSIONS: Activation and terminal complement pathway components are elevated in patients with PCOS, especially in the presence of insulin resistance and obesity.