Clinical perspectives for D-chiroinositol dose-dependent supplementation in estrogen-dependent hyperproliferative gynecological diseases

D-chiroinositol (D-CI) is an endogenous molecule that plays a key role in the insulin signaling cascade. Insulin promotes the release of inositolphosphoglycans, which contain D-CI so that D-CI deficiency in cells and tissues is directly related to insulin resistance. The mechanism of action of all insulin sensitizers is linked to increasing free D-CI concentration. However, the role of D-CI in vivo is not limited to mediating insulin signal transduction, as it is also involved in the dose-dependent regulation of various other essential physiological processes. This enables D-CI-level-based modulation of distinct physiological functions. D-CI dose-dependently modulates the activity of key steroidogenic enzymes, including 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase, and aromatase. It also exhibits anti-inflammatory and anti-tumor properties by downmodulating levels of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa B (NF-κB), as well as suppressing integrin β3 (protein that in humans is encoded by the ITGB3 gene) gene expression. These effects underpin potential D-CI therapeutic efficacy in managing a broad spectrum of reproductive system disorders. D-CI-related multifaceted effects on insulin resistance, steroidogenesis regulation, and inflammation position this molecule as a promising pharmaconutrient for correcting a wide range of conditions – spanning from insulin resistance syndrome with hyperandrogenism in polycystic ovary syndrome to hyperproliferative, estrogen-dependent diseases such as endometriosis, uterine fibroids, endometrial hyperplasia, and fibrocystic breast disease. The selection of appropriate D-CI daily dosage is a critical determinant underlying its full clinical efficacy.