Metformin and/or Clomiphene Do Not Adversely Affect Liver or Renal Function in Women with Polycystic Ovary Syndrome

CONTEXT: Nonalcoholic fatty liver disease is common to insulin-resistant states such as polycystic ovary syndrome (PCOS). Metformin (MET) is often used to treat PCOS but information is limited as to its effects on liver function. OBJECTIVE: We sought to determine the effects of MET on serum hepatic parameters in PCOS patients. DESIGN: This was a secondary analysis of a randomized, doubled-blind trial from 2002–2004. SETTING: This multi-center clinical trial was conducted in academic centers. PATIENTS: Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included. INTERVENTIONS: Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months. MAIN OUTCOME MEASURE: The percent change from baseline in renal and liver function between- and within-treatment arms was assessed. RESULTS: Renal function improved in all treatment arms with significant decreases in serum blood urea nitrogen levels (range, −14.7 to −21.3%) as well as creatinine (−4.2 to −6.9%). There were similar decreases in liver transaminase levels in the clomiphene citrate and combined arms (−10% in bilirubin, −9 to −11% in transaminases) without significant changes in the MET arm. When categorizing baseline bilirubin, aspartate aminotransferase, and alanine aminotransferase into tertiles, there were significant within-treatment arm differences between the tertiles with the highest tertile having the largest decrease from baseline regardless of treatment arm. CONCLUSION: Women with PCOS can safely use metformin and clomiphene even in the setting of mildly abnormal liver function parameters, and both result in improved renal function.