Inositol in Polycystic Ovary Syndrome: Restoring Fertility through a Pathophysiology-Based Approach

Myo-inositol (MI) and D-chiro-inositol (DCI) are insulin second messengers, and MI is involved in follicular gonadotropin pathways which orchestrate ovulation. The tissue-specific MI/DCI ratio is modulated by insulin through aromatase and is altered in insulin resistance (IR), with reduced epimerization of MI to DCI in insulin-sensitive tissues. In ovaries, the MI/DCI ratio is 100:1, but is dramatically reduced by insulin-stimulated epimerase in hyperinsulinemic women with polycystic ovary syndrome (PCOS). Inositols have proved to be effective in PCOS, improving metabolic and hormonal state, and restoring spontaneous ovulation. In assisted reproductive technology, inositol improved ovarian stimulation parameters, although data concerning fertility outcomes are conflicting. Given their functions, inositols are an attractive treatment option for PCOS, although well-designed studies on spontaneous and non-spontaneous fertility are needed. PCOS is a heterogeneous, multifaceted, and complex disorder associated with metabolic and hormonal impairments, ovarian dysfunction, menstrual irregularity, and infertility. PCOS results from a vicious circle of androgen excess favoring abdominal adipose tissue deposition and visceral adiposity by inducing insulin resistance and compensatory hyperinsulinism which further facilitates androgen secretion by the ovaries and adrenal glands. Oral supplementation with MI, DCI, or their combination can improve metabolic patterns and ovarian function in PCOS patients. An MI:DCI ratio of 40:1 is considered an appropriate strategy to improve fertility outcomes, whereas an excess of DCI may have a detrimental effect on oocyte development.