D-chiro-inositol in clinical practice: A perspective from The Experts Group on Inositol in Basic and Clinical Research (EGOI).

BACKGROUND: D-chiro-inositol is a natural molecule that, in association with its well-studied isomer myo-inositol, may play a role in treating various metabolic and gynecological disorders. OBJECTIVES: This perspective seeks to explore the mechanisms and functions of D-chiro-inositol, laying the foundations to discuss its use in clinical practice, across dysmetabolism, obesity, and hormonal dysregulation. METHODS: A narrative review of all the relevant papers known to the authors was conducted. OUTCOME: D-chiro-inositol acts through a variety of mechanisms, acting as an insulin sensitizer, inhibiting the transcription of aromatase, in addition to modulating white adipose tissue/brown adipose tissue trans differentiation. These different modes of action have potential applications in a variety of therapeutic fields including: PCOS, dysmetabolism, obesity, hypoestrogenic/hyperandrogenic disorders, and bone health. CONCLUSIONS: D-chiro-inositol mode of action has been studied in detail in recent years, resulting in a clear differentiation between D-chiro-inositol and its isomer myo-inositol. The insulin sensitizing activities of D-chiro-inositol are well understood; however, its potential applications in other fields, in particular obesity and hyperestrogenic/hypoandrogenic disorders in men and women, represent promising avenues of research that require further clinical study.

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.

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.

Actaea racemosa L. Is More Effective in Combination with Rhodiola rosea L. for Relief of Menopausal Symptoms: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: The aim of this study was to assess the efficacy and safety of a new herbal preparation (Menopause Relief EP®), the hybrid combination of Actaea racemosa L. (black cohosh, BC) and Rhodiola rosea L. (RR) root extracts, compared with the most effective dose of BC extract in women with menopausal complaints. Methods: A total of 220 women were randomly assigned to receive two capsules either BC (6.5 mg), BC500 (500 mg), Menopause Relief EP® (206,5), or placebo once per day for 12 weeks. The efficacy endpoints were relief of menopausal symptoms, measured using the Kupperman Menopausal Index (KMI), Menopause Relief Score (MRS), and menopause Utian Quality of Life (UQOL) index. Results: The menopause symptom relief effects of RR-BC were significantly superior in all tests to the effects of BC and placebo after their repeated administration for 6 and 12 weeks. There was no statistically significant difference between the effects of BC and BC500 over time. RR-BC significantly improved the QOL index in patients, compared to BC, BC500, and placebo, mainly due to the beneficial effects on the emotional and health domains. Conclusions: BC is more effective in combination with RR in relief of menopausal symptoms, particularly psychological symptoms.

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.

Myo-Inositol in the Treatment of Teenagers Affected by PCOS.

Objective. To compare the effectiveness of myo-inositol (MI) and oral contraceptive pills (OCPs) in monotherapy and MI in combination with OCPs in the treatment of teenagers affected by polycystic ovary syndrome (PCOS). Methods. 61 adolescent girls aged 13-19 years, with PCOS, were involved in the prospective, open-label study. Patients were randomized into three groups: I group, 20 patients receiving drospirenone 3 mg/ethinyl estradiol 30 µg; II group, 20 patients receiving 4 g myo-inositol plus 400 mg folic acid; III group, 21 patients receiving both medications. Results. After receiving MI significant reduction in weight, BMI, glucose, C-peptide, insulin, HOMA-IR, FT, and LH was detected. The levels of SHBG, TT, FAI, DHEA-S, and AMH did not change statistically significantly. After receiving OCPs weight and BMI slightly increased, but metabolic parameters did not change. Combination of MI and OCPs did not change weight and BMI, but reduction in C-peptide, insulin, and HOMA-IR was detected. TT, FT, FAI, DHEA-S, LH, and AMH levels decreased and SHBG increased. Conclusions. Administration of MI is a safe and effective method to prevent and correct metabolic disorders in teenagers affected by PCOS. With combination of MI and OCPs antiandrogenic effects are enhanced, negative impact of OCPs on weight gain is balanced, and metabolic profile is improved.