D-Chiro-Inositol in Endometrial Hyperplasia: A Pilot Study.

Endometrial hyperplasia is a threatening pathology driven by unopposed estrogen stimulus. Moreover, insulin may act on the endometrium, prompting further growth. We aimed at assessing whether D-chiro-Inositol, an insulin sensitizer with estrogen-lowering properties, might improve the condition of patients with simple endometrial hyperplasia without atypia. We enrolled women with simple endometrial hyperplasia without atypia and related symptoms, including abnormal uterine bleeding. We treated the patients with one tablet per day, containing 600 mg of D-chiro-inositol for six months. Patients underwent ultrasound to assess the thickness of the endometrium at baseline, after three months, and at the end of this study. Endometrial thickness went from 10.82 ± 1.15 mm to 8.00 ± 0.81 mm after three months (p < 0.001) and to 6.9 ± 1.06 mm after six months (p < 0.001 versus baseline; p < 0.001 versus three months). D-chiro-inositol treatment also improved heavy menstrual bleeding and the length of menstruation. Despite the fact that our data should be validated in larger studies with appropriate control groups, our promising results support the hypothesis that D-chiro-inositol may represent a useful treatment in the case of endometrial hyperplasia without atypia.

Evaluating the Efficacy of Pervistop®, a New Combination Based on EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on Patients with Human Papilloma Virus (HPV) Persistent Infections and Cervical Lesions: A Pilot Study.

BACKGROUND: The persistence of the HPV infection is a risk factor in the integration of viral DNA in the host genome, leading to transforming events. The lack of therapies for HPV-persistent infections determine an unmet medical need. METHODS: We enrolled forty patients with persistent HPV infections and cervical lesions and divided them into two groups. The women in the treated group received 200 mg epigallocatechin gallate (EGCG), 400 µg folic acid (FA), 1 mg vitamin B12, and 50 mg hyaluronic acid (HA) for 12 weeks. The control group received no treatment. RESULTS: 40 patients completed the study. Fifteen out of 20 women in the control group still had an LSIL at the end of the study. One woman had a decrease in the DNA load, while six had no change and eight had an increase in DNA content. In the treatment group, 17 out of 20 women achieved a full viral clearance. These women showed no cytological or histological evidence of lesions following the treatment. CONCLUSIONS: Our data highlight the possible effect of such combination on LSIL. Therefore, the evidence reported here supports the potential to carry out further randomized placebo-controlled studies with an adequate number of patients to verify our results.

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.

D-chiro-inositol Induces Ovulation in Non-Polycystic Ovary Syndrome (PCOS), Non-Insulin-Resistant Young Women, Likely by Modulating Aromatase Expression: A Report of 2 Cases.

BACKGROUND Anovulation consists in the lack of oocyte release during the menstrual cycle, leading to an irregular menstrual cycle. Untreated chronic anovulation is one of the major causes of female infertility and can induce hypoestrogenism. Different etiological factors can contribute to anovulation; therefore, the clinical approaches to manage this condition should take into account the specific patient characteristics. Oral ovulation-inducing agents are first-line treatments for most anovulatory patients. Drugs used include selective estrogen receptor modulators (SERMs) such as clomiphene citrate and aromatase inhibitors (AIs) such as letrozole. The latter, in particular, halts the estrogen biosynthesis by blocking the activity of steroidogenic enzyme aromatase, which catalyzes the conversion of androgens to estrogens. Similarly, d-chiro-inositol (DCI) modulates the activity of aromatase by reducing the corresponding gene expression, and DCI supplementation was successfully used to induce ovulation in anovulatory PCOS patients. Here, we report the use of DCI to induce ovulation in non-PCOS anovulatory oligomenorrheic women. CASE REPORT Two young non-PCOS anovulatory oligomenorrheic women received treatment with high-dose (1200 mg) DCI for 6 weeks. Based on an initial evaluation, both patients had normal hormone levels and were non-insulin-resistant. Ovulation assessment was based on the increment of progesterone and LH levels, as well as on the endometrial thickening. Also, the treatment with DCI resulted in a reduction of testosterone levels relative to baseline values. CONCLUSIONS After the 6-week treatment with 1200 mg DCI, ovulation was restored in both women, as confirmed by increased progesterone and LH and endometrial thickening.

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.