Clinical

Metformin safe in PCOS, even with mild liver dysfunction

Last Updated: 2011-09-23 15:01:24 -0400 (Reuters Health)

By Anne Harding

NEW YORK (Reuters Health) - Metformin is safe for women with polycystic ovary syndrome (PCOS), even if they have mildly abnormal liver function, a new paper reports.

Women with PCOS are sometimes prescribed metformin to improve menstrual regulation, lower androgen levels, and improve glucose tolerance and insulin resistance.

But metformin also carries the rare risk of idiosyncratic hepatitis in type 2 diabetics, and it hasn't been clear, according to the authors of the new paper, whether the drug might also harm the liver in women with PCOS.

That's why Dr. Richard S. Legro from Pennsylvania State College of Medicine in Hershey and colleagues conducted a post hoc analysis of data from a randomized trial conducted in 626 infertile women with PCOS who wished to become pregnant.

Women in the study took either metformin, clomiphene citrate, or both for up to six months. Women were excluded if their alanine aminotransferase (ALT) level was twice the upper limit of normal, the researchers reported online August 10th in the Journal of Clinical Endocrinology and Metabolism,

Mean blood urea nitrogen levels fell in all groups, with reductions ranging from 14.7% to 21.3%. Creatinine levels also fell in each group, by 4.2% to 6.4%. Total bilirubin dropped by about 10% in the clomiphene and combination groups, vs. less than 1% in the metformin group. Aspartate aminotransferase (AST) levels and ALT levels also fell, again with greater reductions in the clomiphene and combination groups compared to the metformin group.

Women in the highest tertile transaminase and bilirubin levels had the largest reduction in these parameters, no matter which treatment group they were in.

"Liver function is not altered by taking metformin, and may even be improved in patients with higher liver function at the beginning of the study," Dr. Legro said in an interview. "One of the benefits of metformin is it is renally excreted, so there's no hepatic metabolism of metformin, so theoretically liver function shouldn't even function in a decision-making process."

Based on the findings, he and his colleagues say, monitoring liver and renal function every six months, or at even longer intervals, is likely safe in PCOS patients on metformin. "Probably we're safe monitoring every year," Dr. Legros said.

He said most doctors who prescribe metformin for PCOS are family doctors and OB/GYNs, who traditionally don't monitor renal and liver function on the same schedule an internist would use for a patient taking multiple medications.

"We're trying to establish the window of monitoring where we can safely detect abnormal changes, and I think the longer we can push out the window the more likely clinicians are going to be to use the medication," he added. "There's a number of benefits, and there's many reasons for why women should be on these drugs."

"We put this article out there to reassure people that liver function is unlikely to worsen on it, and in many cases can get better," he concluded.

SOURCE: http://bit.ly/q1kh1M

J Clin Endocrinol Metab 2011.