Non-alcoholic fatty liver disease is associated with hyperandrogenism in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53-6.63) in FT; 1.12 (1.04-1.22) in FAI), FLI (OR 2.68 (95% CI 1.43-5.03) in FT; 1.13 (1.06-1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08-5.21) in FT; 1.5 (1.09-1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS.