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

J Clin Endocrinol Metab. 2011 Oct;96(10):E1645-9. doi: 10.1210/jc.2011-1093. Epub 2011 Aug 10.

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.

Publication types

  • Meta-Analysis
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Bilirubin / blood
  • Clomiphene / adverse effects*
  • Clomiphene / therapeutic use
  • Double-Blind Method
  • Female
  • Fertility Agents, Female / adverse effects*
  • Fertility Agents, Female / therapeutic use
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Infertility, Female / drug therapy
  • Kidney / drug effects*
  • Kidney Function Tests
  • Liver / drug effects*
  • Liver Function Tests
  • Metformin / adverse effects*
  • Metformin / therapeutic use
  • Polycystic Ovary Syndrome / metabolism*

Substances

  • Fertility Agents, Female
  • Hypoglycemic Agents
  • Clomiphene
  • Metformin
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Bilirubin

Associated data

  • ClinicalTrials.gov/NCT00068861