Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients.

OBJECTIVE: To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients. METHODS: This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated. RESULTS: ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease. CONCLUSION: ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.

Low-Dose Estrogens as Neuroendocrine Modulators in Functional Hypothalamic Amenorrhea (FHA): The Putative Triggering of the Positive Feedback Mechanism(s).

Functional hypothalamic amenorrhea (FHA) is a non-organic reversible chronic endocrine disorder characterized by an impaired pulsatile secretion of the gonadotropin-releasing hormone (GnRH) from the hypothalamus. This impaired secretion, triggered by psychosocial and metabolic stressors, leads to an abnormal pituitary production of gonadotropins. As LH and FSH release is defective, the ovarian function is steadily reduced, inducing a systemic hypoestrogenic condition characterized by amenorrhea, vaginal atrophy, mood changes and increased risk of osteoporosis and cardiovascular disease. Diagnosis of FHA is made excluding other possible causes for secondary amenorrhea, and it is based upon the findings of low serum gonadotropins and estradiol (E2) with evidence of precipitating factors (excessive exercise, low weight, stress). Treatments of women with FHA include weight gain through an appropriate diet and physical activity reduction, psychological support, and integrative approach up to estrogen replacement therapy. If no spontaneous ovarian function is restored, assisted reproductive technologies may be used when pregnancy is desired. Because subjects with FHA are hypoestrogenic, the use of low-dose estrogens has been proposed as a putative treatment to positively modulate the spontaneous restart of gonadotropin secretion, counteracting the blockade of the reproductive axis triggered by stress acting through the neuroendocrine pathways at the basis of positive feedback of estrogens. The mechanism through which low-dose estrogens acts is still unknown, but kisspeptin-secreting neurons may be involved.

Exposure to Prolonged Rupture of Membranes at Term Increases the Risk for Ventilatory Support in Uninfected Neonates.

OBJECTIVE: The effects of prolonged rupture of membranes (ROMs) on perinatal outcomes are still unclear, and it remains controversial for the management of those labors. This study aims to evaluate how the exposure of pregnant women to a prolonged ROM (≥ 24 hours) affects maternal and neonatal outcomes. STUDY DESIGN: This retrospective cohort study included singleton pregnant women at term delivering between January 2019 and March 2020 in a tertiary hospital. All relevant sociodemographic, pregnancy, and perinatal variables (maternal age, prepregnancy body mass index, labor, and delivery outcomes) were collected anonymously. Data were compared between the "ROM < 24 hours" and "ROM ≥ 24 hours" study groups. RESULTS: A total of 2,689 dyads were included in the study and divided according to their ROM-delivery time: ROM <24 hours (2,369 women, 88.1%), and ROM ≥ 24 hours (320 women, 11.9%). Maternal baseline characteristics were comparable except for the rate of nulliparous women, which was significantly higher among patients with ROM ≥ 24 hours. No significant differences were found regarding infectious neonatal outcomes. However, mechanical ventilation and continuous positive airway pressure were more common among neonates born after ROM ≥ 24 hours. The greater likelihood of neonatal respiratory distress was also confirmed among infants born to Group-B Streptococcus-negative women with ROM ≥ 24 hours (15 out of 267 neonates, 5.6% vs. 52 out of 1,529 with ROM < 24 hours, 3.4%, p = 0.04). CONCLUSION: According to the actual expectant policy, prolonged ROM is associated with an increased risk of respiratory support in noninfected neonates. Further investigations are required to explain such an association. KEY POINTS: · The management of women with prolonged rupture of membranes is controversial.. · The exposure of pregnant women to a prolonged rupture of membranes affects neonatal outcomes.. · Prolonged rupture of membranes is associated with an increased risk of respiratory support, in group-B Streptococcus-negative neonates..

Putative Complementary Compounds to Counteract Insulin-Resistance in PCOS Patients.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine-metabolic disorder among women at reproductive age. The diagnosis is based on the presence of at least two out of three criteria of the Rotterdam criteria (2003). In the last decades, the dysmetabolic aspect of insulin resistance and compensatory hyperinsulinemia have been taken into account as the additional key features in the etiopathology of PCOS, and they have been widely studied. Since PCOS is a complex and multifactorial syndrome with different clinical manifestations, it is difficult to find the gold standard treatment. Therefore, a great variety of integrative treatments have been reported to counteract insulin resistance. PCOS patients need a tailored therapeutic strategy, according to the patient's BMI, the presence or absence of familiar predisposition to diabetes, and the patient's desire to achieve pregnancy or not. The present review analyzes and discloses the main clinical insight of such complementary substances.

Prelabour rupture of the membranes at term: antibiotic overuse in Italy.

BACKGROUND: The proper management of women with premature rupture of membrane (PROM) and not spontaneously entering in labour remains controversial. The aim of this study was to identify the current management for women with PROM at term according to the Group B Streptococcus (GBS) status across different Italian hospitals. METHODS: Anonymous online survey evaluating: the current practice of women with PROM in terms of management (expectant management vs. induction of labour) and antibiotic prophylaxis according to GBS status. RESULTS: In case of negative GBS status, the 82.4% of respondents wait until 24 hours before labour induction. Antibiotics are administered for prophylaxis in 35.3%, 27.5% and 2% at 18, 12 and 24 hours respectively. The remaining 35.3% of respondents are divided between those using antibiotics only with signs of infections or according to different risk factors (i.e. meconium-stained amniotic fluid or suspected infection). Neonates born from a mother with negative GBS status almost never (90.2%) receive prophylactic antibiotics. In case of positive GBS status, induction is started as soon as possible by 49.1% of respondents; the remnants choose to wait 6 (15.7%), 12 (17.6%), 18 (3.9%) and 24 (13.7%) hours. Antibiotics are administered as soon as possible by 78.4% of clinicians. In the neonates, 51% of neonatologist administer antibiotics upon clinical indications (suspected sepsis); 15.7% use antibiotics routinely or with a short interval between maternal antibiotics and delivery (17.6%). CONCLUSIONS: The management after PROM is highly heterogeneous with an inappropriate extension of antibiotic prophylaxis in cases with negative GBS status.

Familial diabetes predisposes PCOS patients to insulin resistance (IR), reproductive impairment and hepatic dysfunction: effects of d-chiro inositol (DCI) and alpha lipoic acid (ALA) administration on hepatic insulin extraction (HIE) index.

ObjectivePCOS is a syndrome is characterized by 2 out of 3 of the criteria established during the Rotterdam Consensus Conference. Recently the issue of insulin resistance (IR) has caught attention.SubjectsA group of overweight/obese PCOS patients (n = 30) have been evaluated before and after 3 months of daily integrative administration of d-chiro inositol (DCI) (500 mg) and alpha lipoic acid (ALA) (300 mg).MethodsHormonal and metabolic profiles, oral glucose tolerance test (OGTT) for glucose, insulin and C-peptide response were performed in baseline conditions and after DCI plus ALA treatment. Hepatic Insulin Extraction (HIE) index was computed along the OGTT to evaluate the liver ability in degrading insulin.ResultsThe treatment decreased LH, Androstenedione (A), insulin plasma levels, BMI, HOMA index, AST and ALT. Considering patients for the presence (n = 17) or absence of familial diabetes (n = 13), the greatest improvements occurred in the former patients. Insulin response to OGTT was greatly reduced after the treatment interval in PCOS with familial diabetes. HIE computation disclosed that in presence of familial diabetes liver degradation of insulin is reduced thus leaving a higher amount of circulating insulin. DCI plus ALA administration decreased AST and ALT and restored hepatic insulin clearance since HIE profile was improved.ConclusionOur study demonstrates that in overweight/obese PCOS the predisposition to familial diabetes triggers IR not only through the endogenous impaired DCI and ALA synthesis but also through a reduced hepatic clearance of insulin. DCI plus ALA administration positively improved hormonal, metabolic profiles as well as liver function.