Study: Insulin sensitizers in the treatment of PCOS

reference

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

design

This randomized, controlled clinical trial evaluated 120 patients with polycystic ovary syndrome (PCOS) and 14-16 months of infertility. Patients were randomly assigned to receive either 1,500 mg of metformin or 4 grams of myo-inositol plus 400 mcg of folic acid daily. In patients who became pregnant, ovulation induction was performed with recombinant follicle-stimulating hormone (r-FSH) (37.5 units/day) for a maximum of 3 attempts. The primary endpoint was recovery of spontaneous ovulation (measured by weekly monitoring of serum progesterone levels and confirmatory transvaginal ultrasound). Secondary endpoints included resistance to treatment (percentage of patients in whom spontaneous ovulation was not restored), pregnancy rate, and abortion rate.

The study showed a statistically significant difference in the recovery of spontaneous ovulation in patients taking myo-inositol versus metformin.

Key findings

Spontaneous ovulation resumed in 50% of patients who received metformin, and 18.3% of them achieved pregnancy. Spontaneous ovulation recurred in 65% of patients treated with myo-inositol, and 30% of them achieved pregnancy. In the remaining patients who did not respond to monotherapy, r-FSH was additionally administered. There were 11 pregnancies in each of the two groups (metformin plus r-FSH group or myoinositol and folic acid plus r-FSH group). Overall pregnancy rates were 36.6% in patients receiving metformin and 48.4% in patients receiving myo-inositol. The study showed a statistically significant difference in the recovery of spontaneous ovulation in patients taking myo-inositol versus metformin. There was an overall higher pregnancy rate in the myo-inositol group, but the effect was not significant.

Effects on practice

A metabolic feature commonly 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 nonoxidative and oxidative glucose disposal.¹The administration of myo-inositol can accelerate glucose utilization and sensitize insulin action. This can reduce the hyperinsulinemic state, which can prevent proper secretion of luteinizing hormone (LH).²

Previous studies have shown that myo-inositol can restore spontaneous ovarian activity and therefore fertility in patients with PCOS.^3.4This study is the first to compare the effectiveness of two insulin sensitizing agents, inositol and metformin, in the treatment of chronic anovulation and infertility secondary to PCOS.

In this study, myo-inositol provided a significant advantage over metformin in restoring spontaneous ovulation in patients with PCOS. This also led to a non-significant increase in the pregnancy rate. In addition, patients taking 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 who experience chronic anovulation or infertility secondary to anovulation.