Insulin Sensitizers and Polycystic Ovary Syndrome

I’ve recently received some requests to address the role of insulin sensitizers for the treatment of polycystic ovary syndrome, in particular D-chiro-inositol. Here are my thoughts as of 7-23-2012.

Many women with PCOS have insulin resistance, and there are a variety of drugs which improve insulin sensitivity. These drugs include metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol, and myo-inositol. Their actions on insulin release and action are rather complex, but it is useful to just consider them all as acting to improve the effect of insulin in the body.

Now, I think there is fairly good evidence that treatment with an insulin sensitizer improves ovarian function in women with PCOS. (Yes, I did participate in one of the largest trials of metformin for PCOS ever performed, which showed no benefit of metformin, but please hear me out.) Metformin is by far the most commonly used insulin sensitizer in PCOS patients. My take on the medical literature is that metformin is most beneficial in PCOS patients who are obese. (The study I participated in wasn’t sufficiently powered to show this, but in that study the ovulation rate in PCOS patients with BMI over 34 who were on clomiphene was improved by adding metformin) . It does promote weight loss in these women, which probably ameliorates the syndrome a bit, but it also has some action independent of weight loss. In particular, metformin may improve the response to clomiphene in obese PCOS patients (and that is the patient for whom I most commonly prescribe metformin). However, clomiphene is much more likely to induce ovulation and pregnancy in PCOS patients than metformin. I often start obese PCOS patients on metformin for a couple of months and then add clomiphene if they are not ovulating on the metformin alone.

There is much less known about the effects of the other insulin sensitizers on PCOS, but they probably have some benefit, too. I don’t use them, though. The published data on the inositol derivatives is limited and contradictory. There is even one paper that claims D-chiro-inositol worsens egg quality in infertile women. More worrisome is that some insulin sensitizers have been shown to have serious side effects, and this information didn’t come to light until the drugs were widely prescribed. Troglitazone (Rezulin) is a good example. Years ago, it was held up as the “next generation metformin”, with better efficacy and fewer side effects. It did work some on PCOS, but it was also found to cause liver failure and was pulled from the market. Pioglitazone (Actos) can cause heart failure.

For now, the only insulin sensitizer I use is metformin, and I don’t use it all that often.

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