PCOS from Lifestyle to the Use of Inositol and Insulin Sensitizers

PCOS patients are typically characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries, and these aspects are frequent in a high percentage of women during the reproductive life. PCOS frequently show overweight and/or obesity and are characterized by a higher production of androgens and reduced sensitivity to insulin. In fact it is of great importance to note that more than 40–45% of all PCOS patients show overweight up to obesity and that these patients have a modest up to an exaggerated hyperinsulinism in response to the standard oral glucose tolerance test (OGTT). What is relevant to point out is that such reduced insulin sensitivity can be observed also in 10–15% of the normal weight PCOS, thus confirming that hyperinsulinism can show up not only in relation to obesity or to excess of fat tissue but also as an intrinsic abnormal ability to control glucose metabolism. Recent data clearly demonstrated that reduced insulin sensitivity can be gained with a specific attention to lifestyle, including not only a diet but also certain degree of physical activity. However, a specific effect on hyperinsulinemia can be achieved using glucose sensitizer drugs, such as metformin, so that to reduce the negative modulation exerted by hyperinsulinemia on the reproductive axis as well as on neuroendocrine control of reproduction with relevant effects also on adrenal function and neurosteroid production. The evolution of therapeutical approach to PCOS proposed in recent years the use of inositol in two of the isomers at present available, that is myo-inositol (MYO) and D-chiro-inositol (DCI). These two compounds are tightly linked one to the other since MYO is transformed by an epimerase in DCI, having each tissue its own conversion rate, likely due to the specific needs for the two different molecules. In general both these compounds work as specific modulators of the intracellular second messenger activated by the insulin linkage with its own membrane receptor. Recent data demonstrated also that integrative administration of MYO in lean PCOS ameliorated insulin response to OGTT and that both MYO and DCI reduced insulin response to OGTT in overweight or obese PCOS. Both isomers have been demonstrated to improve also ovarian function and LH response to GnRH stimulation, typically abnormal in PCOS patients. Though impossible to state what of the two isomers play the main role, it appears clear that the metabolic impairment(s) are great part of the casual factor(s) of the abnormal reproductive function in PCOS.