Metformin and/or clomiphene do not adversely affect liver or renal function in women with polycystic ovary syndrome

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00068861.

Fig. 1.

Percent change in serum liver function tests from baseline for low (T1), mid (T2), and high (T3) tertiles in each treatment arm. A, Bili. B, AST. C, ALT. Error bars represent 95% confidence interval. 1, Value decreased more than low tertile; 2, value decreased more than mid tertile. &, P < 0.05; $, P < 0.01; #, P < 0.001.