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.