Insulin Sensitizers in the Treatment of PCOS

Comparison of inositol and metformin in the treatment of chronic anovulation and infertility secondary to PCOS

By Jaclyn Chasse-Smeaton, ND

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Raffone E, Rizzo P, Benedetto V. Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol. 2010;26(4)275-280.


One hundred twenty patients with polycystic ovarian syndrome (PCOS) and 14–16 months of infertility were studied in this randomized, controlled clinical trial. Patients were randomly assigned to receive either 1,500 mg/day metformin or 4 grams of myo-inositol plus 400 mcg folic acid daily. In patients where in whom pregnancy occurred, patients underwent ovulation induction with recombinant follicle stimulating hormone (r-FSH) (37.5 units/day) for a maximum of 3 attempts. The primary endpoint was restoration of spontaneous ovulation (measured by monitoring serum progesterone levels weekly and transvaginal ultrasound to confirm). Secondary endpoints included resistance to treatment (percentage of patients who did not restore spontaneous ovulation), pregnancy rate, and abortion rate.

The study demonstrated a statistically significant difference in restoration of spontaneous ovulation in patients taking myo-inositol over metformin.

Key Findings

Fifty percent of the patients who received metformin restored spontaneous ovulation, and 18.3% of these achieved pregnancy. Sixty-five percent of patients treated with myo-inositol restored spontaneous ovulation, and 30% of these achieved pregnancy. In the remaining patients who did not respond to monotherapy, r-FSH was added. In each of the 2 groups (metformin plus r-FSH group or myo-inositol and folic acid plus r-FSH group), 11 pregnancies occurred. The total pregnancy rates were 36.6% for patients receiving metformin and 48.4% for patients receiving myo-inositol. The study demonstrated a statistically significant difference in restoration of spontaneous ovulation in patients taking myo-inositol over metformin. There was an overall higher rate of pregnancy in the myo-inositol group, but the effect was not significant.

Practice Implications

One metabolic feature often observed in patients with PCOS is a defect in inositol metabolism. Inositol plays an important role in insulin and glucose metabolism. Inositol accelerates the dephosphorylation of glycogen synthase and pyruvate dehydrogenase, both rate-limiting enzymes of non-oxidative and oxidative glucose disposal.1 Supplying myo-inositol can accelerate glucose disposal and sensitize insulin action. This may decrease the hyperinsulinemic state that can prohibit proper luteinizing hormone (LH) secretion.2

Previous studies have demonstrated that myo-inositol is capable of restoring spontaneous ovarian activity, and consequently fertility, in patients with PCOS.3,4 This study is the first to compare the effectiveness of 2 insulin-sensitizing agents, inositol and metformin, in the treatment of chronic anovulation and infertility secondary to PCOS.

In this study, myo-inositol offered a significant advantage over metformin in restoration of spontaneous ovulation in patients with PCOS. This also resulted in a non-significant increase in pregnancy rate. In addition, patients on myo-inositol reported no side effects during the course of treatment. Myo-inositol should be considered as a first-line treatment in patients with PCOS experiencing chronic anovulation or infertility secondary to anovulation.

About the Author

Jaclyn Chasse-Smeaton, ND, is vice president of scientific & regulatory affairs at Emerson Ecologics and Wellevate and a practicing naturopathic physician specializing in reproductive health and infertility. She also holds an adjunct faculty position at Bastyr University. Chasse is a graduate of Bastyr and has an undergraduate degree in biochemistry and molecular biology. She has coauthored several scientific journal articles in the field of medical biophysics and integrative medicine and has been involved throughout her career in improving healthcare access and education. Chasse is past-president of the American Association of Naturopathic Physicians and the New Hampshire Association of Naturopathic Doctors.


1. Larner J. D-chiro-inositol—its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1):47-60.

2. Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM. Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol. 2008;24(3):139-144.

3. Zacchè MM, Caputo L, Filippis S, Zacchè G, Dindelli M, Ferrari A. Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovarian syndrome. Gynecol Endocrinol. 2009;25(8):508-513.

4. Papaleo E, Unfer V, Baillargeon JP, et al. Myo-inositol in patients with polycystic ovarian syndrome: a novel method for ovulation induction. Gynecol Endocrinol. 2007; 23(12):700-703.