Inositols: From Established Knowledge to Novel Approaches.

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

Experts' opinion on inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: a further help for human reproduction and beyond.

Introduction: This Experts' opinion provides an updated scientific support to gynecologists, obstetricians, endocrinologists, nutritionists, neurologists and general practitioners on the use of Inositols in the therapy of Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM).Areas covered: This paper summarizes the physiology of Myo-Inositol (MI) and D-Chiro-Inositol (DCI), two important molecules present in human organisms, and their therapeutic role, also for treating infertility. Some deep differences between the physiological functions of MI and DCI, as well as their safety and intestinal absorption are discussed. Updates include new evidence on the efficacy exerted in PCOS by the 40:1 MI/DCI ratio, and the innovative approach based on alpha-lactalbumin to overcome the decreased therapeutic efficacy of Inositols in some patients.Expert opinion: The evidence suggests that MI, alone or with DCI in the 40:1 ratio, offers a promising treatment for PCOS and NIDDM. However, additional studies need to evaluate some still unresolved issues, such as the best MI/DCI ratio for treating NIDDM, the potential cost-effectiveness of reduced gonadotropins administration in IVF due to MI treatment, or the benefit of MI supplementation in ovulation induction with clomiphene citrate in PCOS patients.

The value of anti-Mullerian hormone in the management of polycystic ovary syndrome in adolescents.

A prospective study was carried out in 110 adolescents (13-19 years), 90 patients with polycystic ovary syndrome (PCOS) (study group) and 20 healthy adolescents (control group). The study group was divided into two: Group I - patients without insulin resistance (n = 30) and Group II - patients with insulin resistance (n = 60). Group I was treated with oral contraceptives (OCs), while Group II was divided into treatment subgroups of 20 patients each: Subgroup A received OCs; Subgroup B - myo-inositol; subgroup C - OCs + myo-inositol. Data were analyzed at baseline, 3 and 6 months of treatment. Results showed average anti-Mullerian hormone (AMH) levels were significantly higher in PCOS patients (11.8 ± 5.3 ng/ml) than in controls (2.98 ± 4.5 ng/ml). After treatment, in Group I and Group II Subgroup A: AMH, luteinizing hormone (LH), free testosterone (FT), total testosterone (T), Ov/v, antral follicle count (AFC), and Ferriman-Gallwey modified scale (mFG) significantly decreased, homeostatic model assessment-insulin resistance (HOMA-IR), body mass index (BMI) did not change significantly. In Group II Subgroup B only HOMA-IR and BMI significantly decreased; in Subgroup C all the parameters decreased significantly. The correlation between AMH and hormonal, morphological characteristics of ovaries were established. The results indicate that AMH could possibly be a valuable marker for the diagnosis of PCOS in adolescents, and for the assessment of treatment efficacy as well.