Reflections on inositol(s) for PCOS therapy: steps toward success

Abstract

In polycystic ovary syndrome (PCOS) pathogenesis, both the insulin resistance and the related compensatory hyperinsulinemia are involved. Despite their similarities, Myo-inositol (MI) and d-chiro-inositol (DCI) play different roles in PCOS etiology and therapy. Indeed, in tissue such as the liver both molecules are involved in the insulin signaling, i.e. MI promotes glucose uptake and DCI glycogen synthesis. In reproductive tissue such as the ovary, MI regulates glucose uptake and follicle stimulating hormone (FSH) signaling, whereas DCI is devoted to the insulin-mediated androgen production. The new hypothesis on "DCI paradox" in the ovary has provided the key for a better understanding. Unlike other tissues, ovary is not insulin resistant, indeed because the epimerase enzyme, which converts MI to DCI, is insulin dependent, the "DCI paradox" hypothesis suggests that in the ovary of PCOS women, an increased epimerase activity leads to a DCI overproduction and MI depletion. This imbalance could be the cause of the poor oocyte quality and the impairment in the FSH signaling. Owing to this situation, the focal point is the administration of both MI and DCI in a proper ratio for treating PCOS. This topic, with several other "hot" issues, was the driving thread in the discussion between the two scientists.

Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials

“…Indeed, Myo-Ins and D-chiro-Ins have been shown to play different roles in the physiology and treatment of PCOS [15]. In the ovary, D-chiro-Ins is involved in insulin-mediated androgen synthesis [16], whereas Myo-Ins mediates glucose uptake and follicle stimulating hormone (FSH) signaling [14, 15, 17, 18].…”

“…Indeed, Myo-Ins and D-chiro-Ins have been shown to play different roles in the physiology and treatment of PCOS [15]. In the ovary, D-chiro-Ins is involved in insulin-mediated androgen synthesis [16], whereas Myo-Ins mediates glucose uptake and follicle stimulating hormone (FSH) signaling [14, 15, 17, 18]. In human ovaries, 99% of the intracellular pool of inositol consists of Myo-Ins and the remaining part consists of D-chiro-Ins [17]; imbalance of ovarian Myo-Ins and D-chiro-Ins concentrations, like a putative Myo-Ins deficiency, might impair the FSH signaling, as observed in PCOS patients [17–19].…”

Prospective Randomized Study on the Influence of Myoinositol in PCOS Women Undergoing IVF in the Improvement of Oocyte Quality, Fertilization Rate, and Embryo Quality

“…The paradox theory published and discussed by Nestler and Carlomagno [18, 19] suggests that D-Chiro Inositol in not physiological high dosages has a negative impact on the quality of oocytes of PCOS women, as the ovarian epimerase function is not altered in PCOS patients so that the myoinositol levels in the follicular fluids remain low if only D-Chiro-Inositol is supplemented. The Consensus Conference on myoinositol and D-Chiro-Inositol postulated that the future ideal inositol supplementation should therefore contain a ratio of 40 : 1 between myoinositol and D-Chiro-Inositol [20].…”

Inositol(s) from Bench to Bedside in Endocrinology and Gynecology

“…To get straight to the point, whereas the activation of glucose transporters and glucose utilization take place under the regulation of myoinositol, glycogen synthesis is mainly controlled by D-chiroinositol. On the other hand, in the ovary, myoinositol regulates glucose uptake and FSH signaling, while D-chiroinositol modulates insulin-induced androgen synthesis [1, 2]. In physiological conditions, the intracellular pool of inositol(s) in human ovaries and testis contains 99% of myoinositol whereas the remaining part is D-chiroinositol [2, 3].…”