Impact of obesity, insulin resistance and hyperandrogenism on steatosis and fibrosis risk in young females with PCOS

Obesity and insulin resistance (IR) represent a common pathogenic background of polycystic ovary syndrome (PCOS) and nonalcoholic fatty liver disease (NAFLD). We evaluated whether PCOS is a risk factor for steatosis, and subsequently, the impact of IR and hyperandrogenism on steatosis and fibrosis. We considered 202 consecutive non diabetic PCOS patients and 101 age-matched controls. PCOS was diagnosed applying the Rotterdam diagnostic criteria. Steatosis was diagnosed if hepatic steatosis index (HSI) >36, while fibrosis by using the FIB-4 score. As surrogate estimate of insulin sensitivity we considered the insulin sensitivity index (ISI). Free androgen index (FAI) was calculated as estimate of biochemical hyperandrogenism. In the entire population, steatosis was observed in 68.8 and 33.3% (p<0.001) of patients and controls, respectively. In PCOS patients, steatosis was independently linked to waist circumference (OR 1.04, p=0.006) and ISI Matsuda (OR 0.69, p=0.004), not to FAI (OR 1.10, p=0.14). Notably, ISI Matsuda was confirmed as independently associated with steatosis in both obese (OR 0.42, p=0.005) and nonobese (OR 0.69, p=0.009) PCOS patients, while FAI (OR 1.45, p=0.004) resulted an independent risk factor only in nonobese PCOS. Similarly, higher FIB-4 was independently associated with higher FAI (p=0.02) in nonobese and with lower ISI Matsuda (p=0.04) in obese patients. PCOS is an independent risk factor for steatosis. IR and hyperandrogenism, this last especially in nonobese patients, are the key players of liver damage in PCOS.