Inositol Supplementation to Treat Reproductive and Metabolic Dysfunction in Polycystic Ovary Syndrome: A Double Blind RCT (INSUPP-PCOS)

The revised project summary/abstract: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women. It is a heterogeneous syndrome with reproductive dysfunction of chronic anovulation and hyperandrogenism, as well as metabolic dysfunction: insulin resistance, glucose intolerance and metabolic syndrome. One such medication that may improve both aspects of PCOS is inositol and it is available throughout the world as a dietary supplement. More specifically we will study a combination of isomers, d-chiro and myo-inositol. The combination is thought to improve insulin (and gonadotropin) signaling by restoring an imbalance in inositolglycans which are second messengers in cell surface signaling. We propose here the first adequately powered and designed clinical trial to test prospectively the effects of inositol supplementation in a dose ranging double blind randomized controlled trial, (the INSUPP- PCOS study) according to CONSORT guidelines. This will be a four armed study of three doses of inositol vs. placebo over a three month period with the reduction in hyperandrogenism (based on serum testosterone levels) as the primary outcome and key secondary outcomes of the change in sex hormone binding globulin(SHBG) and the related free androgen index, fasting insulin levels and area under the curve glucose levels from an oral glucose challenge test (OGTT). The hypothesis is that women with PCOS who receive inositol supplementation will have a dose related reduction in hyperandrogenism. Further, we propose that the primary mechanism of inositol will be a significant improvement in hyperandrogenism (both ovarian and adrenal) vs. placebo, as documented by a lower free androgen index [decreased total testosterone and increased sex hormone blinding globulin (SHBG)], lower sebum measures and lower antral follicle counts of the ovary and anti-Mullerian hormone, all of which will correlate with the decrease in hyperandrogenism. We bring to this study a proven and established team of multi-disciplinary researchers who have successfully conducted multiple related trials. Our trial is highly innovative and significant, as we are studying a widely used supplement that may have a broad indication across all phases of the reproductive lifespan of a woman with PCOS. Further by registering the trial, preparing a written protocol and manual of operations and procedures and by following CONSORT guidelines we will be establishing a rigorous bulwark to allow for replication of our trial.