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.

The Effects of Myo-Inositol and D-Chiro-Inositol in a Ratio 40:1 on Hormonal and Metabolic Profile in Women with Polycystic Ovary Syndrome Classified as Phenotype A by the Rotterdam Criteria and EMS-Type 1 by the EGOI Criteria.

SETTING: Insulin resistance (IR) and compensatory hyperinsulinemia are considered contributing factors toward polycystic ovary syndrome (PCOS). OBJECTIVES: This study evaluates the frequency of metabolic abnormalities in PCOS patients and the effects of myo-inositol (MI) and D-chiro-inositol (DCI), in a 40:1 ratio on hormonal and metabolic parameters. PARTICIPANTS: Thirty-four women with PCOS phenotype A (endocrine-metabolic syndrome [EMS-type 1]) between the ages of 20-40. DESIGN: Open prospective study with phenotype A (EMS-type I, n = 34) supplemented with 2,255 mg/day of inositol (MI and DCI in a 40:1 ratio) for 3 months. METHODS: The following were measured before and after treatment: serum levels of follicular stimulating hormone, luteinizing hormone (LH), estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), anti-Müllerian hormone, glucose, insulin, HOMA-IR, and body mass index (BMI). RESULTS: 55.9% of the enrolled patients were overweight or obese, 50% affected by IR, 17.6% with a history of gestational diabetes mellitus, and 61.8% had familial diabetes mellitus. At the conclusion of the study, BMI (p = 0.0029), HOMA-IR (p < 0.001) significantly decreased, along with decreased numbers of patients with elevated insulin levels. The supplementation resulted in decreased total testosterone (p < 0.001), free testosterone (p < 0.001), FAI (p < 0.001), and LH (p < 0.001); increased SHBG (p < 0.001) and estradiol (p < 0.001). LIMITATIONS: The present analysis was limited to a 12-week follow-up, which precluded a long-term evaluation of the effects of MI and DCI combination. Also, this period was insufficient to achieve and analyze clinical changes such as restoration of the menstrual cycle, restoration of reproductive function, and clinical manifestations of hyperandrogenism. CONCLUSIONS: Supplementation improved metabolic and hormonal profile in PCOS phenotype A (EMS-type I) patients. This builds upon previous work that demonstrated that combined inositol treatment may be effective in PCOS. The study presented herein, used a reduced concentration than in prior literature; however, a significant change in hormonal and metabolic parameters was still observed.

Effects of antibiotic therapy in women with the amniotic fluid "sludge" at 15-24 weeks of gestation on pregnancy outcomes.

Objective: The aim of this prospective study was to assess the efficacy of antibiotic therapy for the prevention of adverse pregnancy outcomes in women with the amniotic fluid "sludge" at 15-24 weeks of gestation.Methods: 245 women underwent transvaginal ultrasound cervical length measurement at 15-24 weeks of pregnancy and 29 out of them with amniotic fluid "sludge" were included in the study. Eight women with the "sludge" had cervical length >25 mm (Group I), seven-an asymptomatic short cervix (Group IIa) and 14 women with a short cervix had symptoms like low abdominal pain, back pain, and menstrual-like cramps (Group IIb). All participants received intravenous, oral and/or vaginal antibiotic therapy. Participants in Group IIa were additionally given vaginal progesterone (VP), and in Group IIb-VP and indomethacin. Placentas from women with preterm birth (PTB) underwent histological examination.Results: The amniotic fluid "sludge" detected at an ultrasound scan between 15-24 weeks of gestation was associated with long-term maternal infections, histological chorioamnionitis, and was viewed as a marker of intra-amniotic infection. Absence of intravenous antibiotic therapy during midtrimester of pregnancy in these women was associated with neonatal infection with intrauterine onset in 61.1%, postpartum endometritis in 23.1%, and rate of PTB 46.2%. Intravenous antibiotic therapy eliminated sonographic presence of the sludge and resulted in prevented of neonatal and postpartum infections, prevented the risk of PTB in women with the cervical length >25 mm, in those with an asymptomatic short cervix receiving VP, and in 70% of symptomatic women with a short cervix, who received them in combination VP/indomethacin. For those women whose approach was not fully beneficial, it allowed to delay delivery in 11-17 weeks.Conclusions: Although we found that intravenous antibiotic therapy at 15-24 weeks of gestation in women with amniotic fluid "sludge" can protect from infection-related complications and demonstrated high beneficial effects of adding antibiotics to anti-inflammatory drug (indomethacin) and/or VP in women with a short cervix, further larger studies are needed.

Effectiveness of dydrogesterone, 17-OH progesterone and micronized progesterone in prevention of preterm birth in women with a short cervix.

OBJECTIVE: To compare the efficacy of dydrogesterone, 17-OH progesterone (17OHP) and oral or vaginal micronized progesterone with cerclage for the prevention of preterm birth in women with a short cervix. METHODS: The study included 95 women with singleton gestation and cervical length (CL) ≤ 25 mm. Among these, 35 women were asymptomatic at 15-24 weeks and 60 had symptoms of threatened late miscarriage (LM) or preterm delivery (PD) at 15-32 weeks. Patients were randomized to receive dydrogesterone, 17OHP or oral/vaginal micronized progesterone; after one week of therapy 15 women underwent cerclage. RESULTS: Efficacy of vaginal progesterone (VP) for the prevention of preterm birth reached 94.1%. In asymptomatic women pregnancy outcomes were comparable to cerclage. In women with threatened LM/PD, combination therapy with VP, indomethacin and treatment of bacterial vaginosis (BV) with the subsequent use VP until 36 weeks together with CL monitoring significantly decreased the rate of preterm birth (RR 0.01; 0.0001-0.24) and low birth weight (LBW) (RR 0.04; 0.01-0.96). CL increase during the first week of treatment with a subsequent plateau phase indicated treatment efficacy. Dydrogesterone, 17OHP, and micronized oral progesterone (OP) were associated with PD in 91.7% of women. CONCLUSIONS: Combination management strategy including VP significantly benefits pregnancy outcomes in women with a short cervix compared with cerclage. Dydrogesterone, 17OHP, and OP were not found to be efficacious.

Management of mastitis and breast engorgement in breastfeeding women.

OBJECTIVE: To identify the best management approaches to mastitis management in breastfeeding women and heavy breast engorgement in the early postnatal period. METHODS: We compared various international guidelines and reviews on mastitis management in breastfeeding women and breast engorgement treatment. RESULTS: Effective milk removal is recommended as a first step in mastitis management. Active emptying of the breasts can prevent mastitis development in most cases. If it fails, antibiotics should be administered for 10-14 days with continuing breastfeeding. Russian guidelines recommend antibiotic therapy during 5-7 days with temporary bromocriptine-induced breastfeeding suppression. In case of heavy breast engorgement after lactation is initiated, Progesterone-containing gel can be administered. Application of the progesterone-containing gel on the breast skin improves swelling, and reduces engorgement and tenderness in 15-20 minutes. CONCLUSIONS: Antibiotics with temporary suppression of breastfeeding are more effective than with continuing breastfeeding in mastitis management. The progesterone-containing gel is recommended on the 3rd-4th days after childbirth in heavy breast engorgement to prevent mastitis.