Prevalence of Non-alcoholic Fatty Liver Disease in Polycystic Ovary Syndrome

The prevalence of non-alcoholic fatty liver disease (NAFLD) in polycystic ovary syndrome (PCOS) has not been previously described.  As insulin resistance has been implicated in the pathogenesis of both NAFLD and PCOS, we hypothesized that NAFLD would be common in PCOS.  We performed a retrospective study of 88 consecutive pre-menopausal subjects (median age 31.4 years, interquartile range 24.1-36.9 years; median BMI 26.9 kg/m², interquartile range 22.0-36.2 kg/m²) with PCOS from a single private endocrinology practice in New York City.  Patients denied heavy alcohol use and known liver disease; all met the 1990 NIH criteria for PCOS, namely menstrual dysfunction and hyperandrogenism with the exclusion of other causes.  The severity of hepatic steatosis by ultrasound (US) was graded as none, mild, moderate, or severe by radiological criteria.  Patients were grouped by BMI, where lean denoted BMI<25 kg/m², overweight denoted BMI≥25 but <30 kg/m², and obese denoted BMI≥30 kg/m².  Treatment with metformin was noted in 46, oral contraceptives in 32, neither in 32, and both in 22 subjects; 3 had type 2 diabetes.  Forty eight (55%) had steatosis by US criteria.  Higher BMI group was associated with increasing grade of steatosis, stratifying on treatment with oral contraceptive, metformin, neither, or both (Cochran-Mantel-Haenszel test, p=0.0005).  In addition, the presence of steatosis was associated with a greater median BMI (31.3 vs. 24.3 kg/m², p=0.005) and pre-metformin HOMA-IR (3.53 vs. 1.50 mmol mIU/L², p=0.033) and lower median fasting HDL cholesterol (54 vs. 64 mg/dL, p=0.003) by the Mann-Whitney U test.  There were no significant differences in median age, fasting glucose, fasting insulin, total cholesterol, LDL cholesterol, or triglycerides in those with and without steatosis with a=0.05.  Of note, only 7 of the 48 subjects with steatosis (15%) had abnormal liver chemistries.  We conclude that hepatic steatosis is common in women with PCOS and even in lean patients.  High BMI and insulin resistance appear to be important factors.  As non-alcoholic steatohepatitis is a risk factor for the development of cirrhosis and hepatocellular carcinoma, high prevalence of hepatic steatosis in this population of otherwise healthy young women with mostly normal liver chemistries is a concern.

Table.  Prevalence and severity of steatosis by BMI group.