Variations in alanine aminotransferase levels within the normal range predict metabolic and androgenic phenotypes in women of reproductive age

Background and aims. Obesity plays pathogenetic roles in nonalcoholic fatty liver disease (NAFLD) and hyperandrogenic states like polycystic ovary syndrome (PCOS). We tested the hypothesis that alanine aminotransferase (ALT), a marker of NAFLD, is associated with endocrine and metabolic abnormalities in women with normal ALT. Methods and results. Fasting glucose, insulin, total testosterone, DHEA-S, 17-hydroxyprogesterone, prolactin, leptin, soluble leptin receptor, free leptin index (FLI), lipid profile, ALT, gonadotropins, and sex hormone binding globulin (SHBG) were measured in 200 women aged 18-48 years. Beta cell function (%B), insulin sensitivity (%S) and insulin resistance were calculated using the homeostasis model assessment (HOMA-IR). Ninety-two women had PCOS (Rotterdam criteria); 64 had idiopathic hyperandrogenism; 44 were normal controls. ALT showed significant positive correlations with waist circumference (WC), systolic blood pressure, glucose, leptin, FLI, triglycerides, HOMA-IR and androgens and significant inverse correlations with leptin receptor, HDL-C, %S and SHBG. Correcting for WC and fat% showed that the associations between ALT and glucose, HOMA-IR, testosterone and free androgen index are independent of obesity. Binary logistic regression analyses showed significant association of ALT with PCOS and hyperandrogenemia. ALT >= 18 IU/L showed significant association with PCOS with Odds Ratio = 2.28 (95% Confidence Interval = 1.03-5.08), p = 0.043. Conclusions. In women of reproductive age, normal levels of ALT are associated with metabolic and androgenic phenotypes. We suggest a paradigm shift and extension of the routine use of ALT beyond the diagnosis of liver disease.