Search

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.

INTRODUCTION: In both diabetic subjects and animal models high levels of vasopressin (AVP) have beendetected. The relationship between AVP and glucose metabolism is mediated through several direct andindirect effects and most of them are still unknown. METHODS: We have reviewed 100 manuscripts retrieved from Cochrane Library, Embase and Pubmeddatabases in order to highlight a possible relationship between copeptin and type 2 diabetes and to provideinsights on the molecular mechanism that could explain this association. RESULTS AND CONCLUSIONS: AVP potentiates CRH action at pituitary level resulting in an increased ACTH secretion and in turn in an increased cortisol secretion that escapes the negative feedback loop. Further, AVP regulates insulin and glucagon secretion through V1b receptor and promotes hepatic glycogenolysis and gluconeogenesis through V1a receptor. In addition to worsen glucose metabolism, AVP has been reported to have a role in the pathogenesis of diabetic complications such as cardiovascular diseases, kidney and ocular complications. Due to the very low concentration of AVP in the blood, the small size and poor stability, the assay of AVP is very difficult to perform. Thus, copeptin, the stable C-terminal portion of the prepro-vasopressin peptide has been identified as an easier assay to be measured and that mirrors AVP activity. Although there are promising evidence that copeptin could be involved in the pathogenesis of type 2 diabetes, further studies need to demonstrate the importance of copeptin as clinical marker to predict glucose metabolism derangements.

Kidney transplant is the treatment of choice for end-stage chronic kidney disease. Kidneys generate 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (calcidiol) for circulation in the blood to regulate calcium levels. Transplant patients with low calcidiol levels have an increased risk of metabolic and endocrine problems, cardiovascular disease, type 2 diabetes mellitus, poor graft survival, bone disorders, cancer, and mortality rate. The recommended calcidiol level after transplant is at least 30 ng/mL (75 nmol/L), which could require 1000-3000 IU/d vitamin D3 to achieve. Vitamin D3 supplementation studies have found improved endothelial function and acute rejection episodes. However, since kidney function may still be impaired, raising calcidiol levels may not lead to normal calcitriol levels. Thus, supplementation with calcitriol or an analog, alfacalcidiol, is often employed. Some beneficial effects found include possible improved bone health and reduced risk of chronic allograft nephropathy and cancer.

In the last decades several studies suggested that vitamin D is involved in the modulation of the reproductive process in women due to the expression of VDR and 1α-hydroxylase in reproductive tissues such as ovary, uterus, placenta, pituitary and hypothalamus. Vitamin D has also a role in the regulation of sex hormone steroidogenesis. Increasing evidence suggests that vitamin D might have a regulatory role in polycystic ovary syndrome (PCOS)-associated symptoms, including ovulatory dysfunction, insulin resistance and hyperandrogenism. Vitamin D deficiency also has been reported to contribute to the pathogenesis of endometriosis due to its immunomodulatory and anti-inflammatory properties. Although most of the studies supported a role of vitamin D in the onset of these diseases, randomized controlled trials to assess the efficacy of vitamin D supplementation have never been performed. In this review we critically discuss the role of vitamin D in female fertility, starting from in vitro and in vivo studies, focusing our attention on the two most frequent causes of female infertility: PCOS and endometriosis.

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women and is characterized by two of the following three features: oligoovulation or anovulation, clinical and/or biochemical signs of hyperandrogenism, or polycystic ovaries. Summary It has been demonstrated that PCOS includes a complex number of systemic symptoms in addition to symptoms related to the reproductive apparatus. It has been associated with obesity, metabolic syndrome, type 2 diabetes and an increased risk of cardiovascular disease. Several clinical and basic studies have investigated the link between PCOS and the cardiovascular disease risk, which seems to be due to blunted lipid/glucose metabolism, hypertension, and systemic inflammatory and coagulation disorders. Therefore, the current manuscript aims to review the main findings on PCOS and obesity/ obesity-related disease (glucose derangements and cardiovascular disease risk factors). Key message Although there are no long-term data on the morbidity and mortality for cardiovascular disease in PCOS, it is advisable to perform a careful metabolic and cardiovascular assessment in women with PCOS in order to tailor the most suitable strategy to prevent cardiovascular disease.

AIM: The objective of this study was to investigate the effect of implementation of short-term patient empowerment as applied to Mediterranean diet (MD) adherence on metabolic and anthropometric parameters in prediabetic overweight or obese subjects. METHODS: The sample included 42 subjects with prediabetes, aged 18-75 years and with body mass index (BMI) > 25 kg/m2, who received dietary advice on MD by nutritionists during session groups every 2 weeks for 4 months. Data on energy caloric intake and macronutrient consumption were collected using a 7-day food diary record. Adherence to MD was investigated through the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. No advice was given regarding caloric restriction and physical activity. At baseline and at the end of the study, each subject underwent anthropometric, metabolic, and nutritional assessments. RESULTS: Approximately 40.5% of subjects had achieved restoration of normal glucose tolerance by the end of the study. Fasting plasma glucose, glycated hemoglobin (HbA1C), BMI, waist circumference, blood pressure, visceral adiposity index, triglycerides, and total and LDL cholesterol levels were significantly decreased, while HDL cholesterol had significantly increased by the end of the study. The subjects significantly increased adherence to MD, as assessed by the PREDIMED questionnaire at follow-up. A reduction of prevalence of the metabolic syndrome was also reported. Interestingly, the PREDIMED score correlated with HbA1C values at follow-up, after adjusting for BMI and total caloric intake. CONCLUSIONS: Implementation of short-term patient empowerment as applied to MD adherence was shown to improve anthropometric and metabolic parameters in prediabetic overweight or obese subjects. This is of considerable importance, given that diet must be the cornerstone of treatment in patients at high risk of developing type 2 diabetes.

Background: The main components of GH/insulin-like growth factor (IGF)-1 axis and Sirtuin 4 (Sirt4), highly expressed in liver and skeletal muscle mitochondria, serve as active regulators of mitochondrial oxidative capacity with opposite functions. In obesity both GH/IGF-1 status and serum Sirt4 levels, likely mirroring its reduced mitochondrial expression, might be altered. Objective: To evaluate the association between circulating levels of Sirt4, body composition, metabolic parameters and cardio-metabolic risk profile in obese patients according to their different GH/IGF-1 status. Design: Cross-sectional study with measurement of serum Sirt4, GH after GH releasing hormone (GHRH)+Arginine test, IGF-1 and assessment of body composition, glucose and lipid metabolism in 50 class II-III obese subjects (BMI 35.6 to 62.1kg/m2) and 15 normal weight subjects. Low GH secretion and IGF-1 were defined using pre-determined cutoff-points. The Homeostatic Metabolic Assessment of insulin resistance index and Visceral adiposity index were also calculated. The association of Sirt4 with peak stimulated GH and IGF-1, body composition, metabolic parameters and cardio-metabolic risk profile was assessed. Results: Serum Sirt4 was inversely related to anthropometric and metabolic parameters and positively related to peak GH and IGF-1. After adjusting for peak GH and IGF-1, the relationships between Sirt4 and BMI became not significant. At multiple regression analysis IGF-1 (p < 0.001) was the independent predictor for Sirt4. Conclusion: There was a close relationship between low IGF-1 and low serum Sirt4. This observation suggested that in obese patients, low GH/IGF-1 status was likely associated with a major compensatory decrease in circulating levels of Sirt4 to oppose to its negative regulator effect on mitochondrial oxidative capacity.

The pathogenetic mechanisms underlying the onset of adrenocortical tumors (ACTs) are still largely unknown. Recently, more attention has been paid to the role of insulin and insulin-like growth factor (IGF) system on general tumor development and progression. Increased levels of insulin, IGF-1 and IGF-2 are associated with tumor cell growth and increased risk of cancer promotion and progression in patients with type 2 diabetes. Insulin resistance and compensatory hyperinsulinemia may play a role in adrenal tumor growth through the activation of insulin and IGF-1 receptors. Interestingly, apparently non-functioning ACTs are often associated with a high prevalence of insulin resistance and metabolic syndrome. However, it is unclear if ACT develops from a primary insulin resistance and compensatory hyperinsulinemia or if insulin resistance is only secondary to the slight cortisol hypersecretion by ACT. The aim of this review is to summarize the current evidence regarding the relationship between hyperinsulinemia and adrenocortical tumors.

Low vitamin D status and obesity have concomitantly reached epidemic levels worldwide. Up to now the direction of the association between low vitamin D status and obesity, the exact mechanisms responsible for this association and the clinical usefulness to increase vitamin D status for reducing adiposity still warrant further evaluation. The aim of the present review was to examine the current evidence linking low vitamin D status and obesity in relation to the role of the nutritionist. On the one side, considering obesity as a causal factor, low sun exposure in obese individuals due to their sedentary lifestyle and less outdoor activity, vitamin D sequestration in adipose tissue, and volumetric dilution of ingested or cutaneously synthesized vitamin D3 in the large fat mass of obese patients, might represent some of the factors playing a major role in the pathogenesis of the low vitamin D status. On the other side, the expression of both vitamin D3 receptors and enzymes responsible for vitamin D3 metabolism in adipocytes depicted a role for the low vitamin D status per se in the development of obesity by modulating adipocyte differentiation and lipid metabolism. Nutritionists need to accurately address the aspects influencing the low vitamin D status in obesity and the vitamin D supplementation in obese individuals.

International audience; The objective was to provide the current state of the art regarding the role of vitamin D in chronic diseases (osteoporosis, cancer, cardiovascular diseases, dementia, autism, type 1 and type 2 diabetes mellitus, male and female fertility). The document was drawn up by panelists that provided their contribution according to their own scientific expertise. Each scientific expert supplied a first draft manuscript on a specific aspect of the document’s topic that was subjected to voting by all experts as “yes” (agreement with the content and/or wording) or “no” (disagreement). The adopted rule was that statements supported by ≥75 % of votes would be immediately accepted, while those with \textless25 % would be rejected outright. Others would be subjected to further discussion and subsequent voting, where ≥67 % support or, in an eventual third round, a majority of ≥50 % would be needed. This document finds that the current evidence support a role for vitamin D in bone health but not in other health conditions. However, subjects with vitamin D deficiency have been found to be at high risk of developing chronic diseases. Therefore, although at the present time there is not sufficient evidence to recommend vitamin D supplementation as treatment of chronic diseases, the treatment of vitamin D deficiency should be desiderable in order to reduce the risk of developing chronic diseases.

Chronic low-grade systemic inflammation represents a mechanism common to many diseases linked to atherosclerosis-related pathways. There is a growing body of evidence indicating that the combination of food quantity and quality along with genetic susceptibility are able to induce the aberrant activation of innate immune signalling, which initially contributes to chronic low-grade inflammation. Liver represents the central player to inflammatory response. Dietary/metabolic factors contribute to the pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD), the main causes of liver disease in the Western world. Enlargement of the spleen, central organ in regulating the inflammation-related immune response, is commonly seen in patients with of NAFLD, depicting the so called "liver-spleen axis." The aim of this review was to provide an at-a-glance overview of the possible bi-directional mechanisms linking nutrition and inflammation, particularly pinpointing the inflammatory effects stemmed by nutrition on "liver-spleen axis." In particular, the role of unhealthy diet, healthy dietary patterns, such as the Mediterranean diet style, dietary vitamins and micronutrients, such as vitamin D or Magnesium, and Glucagon-Like Peptide-1, a well-known incretin released in response to meal intake, will be discussed. The highly variability of the inflammatory response highlights the role of expert nutritionists in refining methodologies apt to assess nutritional epidemiology and to apply appropriate dietary intervention to counteract diet-induced inflammation mechanisms.

Adrenal mass (AM) is a common incidental finding detected during radiological investigations with an estimated incidence of 4%. Subjects with AM do not show any physical signs of adrenal hormonal excess, although they are often insulin resistant. Interestingly, apparently nonfunctioning AMs are often associated with a high prevalence of insulin resistance (IR) and metabolic syndrome. However, it is unclear whether AM develops from a primary IR and compensatory hyperinsulinemia or whether IR is only secondary to the slight cortisol hypersecretion by AM. Further, the degree of IR has been directly reported to correlate to the size of AM, thus allowing one to hypothesize that compensatory hyperinsulinemia to IR could be mitogenic on the adrenal cortex acting through the activation of insulin and insulinlike growth factor 1 receptors. Thus, the aim of the present article is to review the current evidence on the link between AM and compensatory hyperinsulinemia to IR.

Adulthood and childhood obesity is rapidly becoming an epidemic problem and it has a short and long-term impact on health. Short-term consequences are mostly represented by psychological effects; in fact obese children have more chances to develop psychological or psychiatric problems than non-obese children. The main long-term effect is represented by the fact that childhood obesity continues into adulthood obesity and this results in negative effects in young adult life, since obesity increases the risk to develop morbidity and premature mortality. The obesity-related diseases are mostly represented by hypertension, type 2 diabetes, dyslipidemia, cardiovascular diseases. Medical treatment should be discouraged in childhood because of the side effects and it should be only reserved for obese children with related medical complications. Lifestyle changes should be encouraged in both adulthood and childhood obesity. This review focuses on the management of obesity both in adulthood and in childhood, paying particular attention to lifestyle changes that should be recommended.

A growing body of research is currently focused on the role of inositol isomers and in particular myo-inositol (MYO-INS) and D-chiroinositol (DCI) in the treatment of insulin resistance states. Both isomers have been shown to exert insulin-mimetic action and to lower postprandial glucose. Further, insulin resistance-related diseases were associated to derangements in inositol metabolism. Thus, the aim of this review is to provide current evidence on the potential benefits of inositol isomers (MYO-INS and DCI) in the treatment of disease associated to insulin resistance such as polycystic ovary syndrome (PCOS), gestational diabetes, and metabolic syndrome. Finally, molecular insights into inositol insulin-sensitizing effects will be covered focusing on the possible role of inositol glycans as insulin second messengers.

Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called "obesogenic environment". Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity.

Background: Polycystic ovary syndrome (PCOS) is a complex syndrome characterized by reproductive and metabolic implications. Lifestyle changes, such as diet and exercise, are considered first-line treatment for women affected by PCOS. Pharmacologic treatments target the hormonal and metabolic dysregulations associated to the disease such as insulin resistance, anovulation, hirsutism and menstrual irregularities. Objective: To focus on the role of inositol isoforms, as well as Mediterranean and ketogenic diets, as possible therapeutic strategies in PCOS women. Method: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Results: Accumulating evidence suggests that two inositol isoforms, myo- and D-chiro-, may play a pivotal role in re-addressing both hormonal and metabolic parameters toward homeostasis, counteracting the symptoms and signs typical of this syndrome. In addition, studies focused on Mediterranean and ketogenic diet provided positive results in patients affected by obesity and type 2 diabetes, so these dietetic regimens could represent a fascinating dietetic treatment for the management of PCOS. Conclusion: Both the isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS. In spite of accumulating evidence, it is currently not possible to draw firm conclusion(s) about the efficacy of these interventions considering the severe bias due to different samples size, dose, and duration of intervention among the published studies on this topic. Furthermore, future longitudinal cohort studies along with prospective interventional trials may contribute to better clarify the role of Mediterranean and ketogenic diets in the treatment of PCOS.

BACKGROUND: Although oral contraceptives (OCs) are one the most widespread therapy in young polycystic ovary syndrome (PCOS) women and physical exercise represents a crucial first-step in the treatment of overweight and obese PCOS no studies were performed to compare the effects on cardiovascular risk (CVR) of OCs and physical exercise in PCOS. OBJECTIVE: To compare the effects of OCs administration and physical exercise on the CVR clinical hormonal and metabolic parameters in PCOS women. METHODS: One hundred and fifty PCOS women were enrolled and were randomized to OCs (3 mg drospirenone plus 30 mug ethinylestradiol) structured exercise training program (SETP) or polyvitamin tablets. The intervention phase study was of 6 months. Primary outcome was intima-media thickness (IMT) and flow mediated dilation (FMD). Secondary outcomes were clinical hormonal and metabolic changes. RESULTS: A significant reduction of IMT and a significant increase of FMD were observed in the SETP group after treatment. Compared to baseline in the SETP group a significant improvement in anthropometric measures insulin sensitivity indexes lipid profile cardiopulmonary function inflammatory markers and frequency of menses was observed. OCs use was associated with a significant decrease of hyperandrogenism and a significant improvement of frequency of menses. Further OCs use had a neutral effect on CVR risk factors. CONCLUSION: OCs effectively treat hyperandrogenism and menstrual disturbances while SETP is more effective in improving cardiometabolic profile and cardiopulmonary function in PCOS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The aim of this review is to provide a general overview of the possible associations among the vitamin D status, air pollution and obesity. Sunlight exposure accounts in humans for more than 90 % of the production of vitamin D. Among emerging factors influencing sunlight-induced synthesis of vitamin D, prospective and observational studies proved that air pollution constitutes an independent risk factor in the pathogenesis of vitamin D hypovitaminosis. In addition, environmental pollutants can affect risk of obesity when inhaled, in combination with unhealthy diet and lifestyle. In turn, obesity is closely associated with a low vitamin D status and many possible mechanisms have been proposed to explain this association. The associations of air pollution with low vitamin D status on the hand and with obesity on the other hand, could provide a rationale for considering obesity as a further link between air pollution and low vitamin D status. In this respect, a vicious cycle could operate among low vitamin D status, air pollution, and obesity, with additive detrimental effects on cardio-metabolic risk in obese individuals. Besides vitamin D supplementation, nutrient combination, used to maximize the protective effects against air pollution, might also contribute to improve the vitamin D status by attenuating the "obesogen" effects of air pollution.

In 1963 George Mathe announced to the world that he had cured a patient of leukaemia by means of a bone-marrow transplant. Since than much progress has been made and nowadays Hematopoietic Stem Cell Transplantation (HSCT) is considered the most effective treatment of numerous severe haematological diseases. Gynaecological complications in HSCT women represent a serious concern for these patients, but often underestimated by clinicians in the view of Overall Survival. The main gynaecological complications of HSCT are represented by: premature ovarian failure (POF), thrombocytopenia-associated menorrhagia, genital symptoms or sexual problems in course of chronic GVHD (cGVHD), osteoporosis, secondary solid tumours due to immunosuppressive drugs to treat cGVHD and severity of cGVHD, and fertility and pregnancy issues. In particular fertility-related issues are always more relevant for patients, whose life expectation is constantly growing up after HSCT. Thus, taking care of a patient undergoing HSCT should primarily include gynaecological evaluation, even before conditioning regimen or chemotherapy for the underlying malignancy, as, in our opinion, it is of great importance to ensure a complete diagnostic work-up and intervention options to guarantee maximum reproductive health and a better quality of life in HSCT women. The present review aims at describing principal features of the aforementioned gynaecological complications of HSCT, and to define, on the basis of current international literature, a specific protocol for the prevention, diagnosis, management and follow-up of gynaecological complications of both autologous and heterologous transplantation, before and after the procedure.

Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence β-cell function, insulin sensitivity, and systematic inflammation-all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

Summary Objective Foetal exposure to high testosterone concentrations seems to be involved in the development of mammalian brain and related to pervasive developmental disorders (PDDs). The aim of the current study was to test the hypothesis that children born from hyperandrogenic women with polycystic ovary syndrome (PCOS) are at higher risk of PDDs. Design Longitudinal case–control study. Patients Thirty pregnant PCOS patients with hyperandrogenaemia and other 45 pregnant healthy women were followed during pregnancy. All women had a healthy baby. Measurements Clinical evaluations and biochemical assays of the mothers during pregnancy and after delivery were performed. The children’s versions of the Autism-Spectrum Quotient (AQ-C), the Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) tests were administered. Results Total AQ-C and communication scores were significantly higher for children of PCOS patients. Stratifying our population according to sex, total AQ-C, communication and attention switching subscores were significantly higher only for daughters of PCOS patients. EQ-C and SQ-C scores resulted in significantly lower and higher scores, respectively, only in daughters of PCOS patients in comparison with those of healthy nonPCOS controls. AQ-C, EQ-C and SQ-C scores, irrespective of the studied group and/or subclassification by gender, were significantly influenced by amniotic testosterone levels. Conclusions Daughters of mothers affected by hyperandrogenic PCOS seem to have a higher risk for PDDs probably due to an unbalanced prenatal exposure to high levels of testosterone.

Objective To test the hypothesis that the risk of adverse obstetric or neonatal outcomes varies according to different phenotypes of polycystic ovary syndrome (PCOS), and to evaluate the clinical impact of the main features of PCOS. Design Prospective controlled clinical study. Setting Academic Departments of Obstetrics and Gynecology, and of Endocrinology, Italy. Patient(s) Ninety-seven pregnant women with PCOS and 73 healthy pregnant subjects were recruited as cases and controls, respectively. Intervention(s) Clinical, biochemical, and ultrasonographic evaluations. Main Outcome Measure(s) Obstetric and neonatal outcomes. Result(s) The relative risk (RR) for adverse obstetric or neonatal outcomes was increased (1.7, 95% confidence interval [CI] 1.12–2.96) in patients with PCOS and varied according to the PCOS phenotype (1.93, 95% CI 1.12–2.96; 2.23, 95% CI 1.21–3.15; 0.54, 95% CI 0.09–1.63, and 0.48, 95% CI 0.31–0.78 for full-blown, nonpolycystic ovaries [PCO], nonhyperandrogenic, and ovulatory phenotypes, respectively). The RRs were 1.57 (95% CI 0.85–2.52) and 0.48 (95% CI 0.31–0.78) for oligoanovulatory and ovulatory patients with PCOS, respectively. The risk for adverse obstetric or neonatal outcomes was affected significantly by ovarian dysfunction and biochemical hyperandrogenism, whereas no significant effect was detected for clinical hyperandrogenism and PCO. Conclusion(s) The increased risk for adverse obstetric and neonatal outcomes that was observed in patients with PCOS varies widely according to the different phenotypes and features of PCOS.

Please cite this paper as: Palomba S, Falbo A, Russo T, Battista L, Tolino A, Orio F, Zullo F. Uterine blood flow in pregnant patients with polycystic ovary syndrome: relationships with clinical outcomes. BJOG 2010; DOI: 10.1111/j.1471-0528.2010.02525.x. Objective To study the impedance to blood flow through the uterine artery in pregnant women with polycystic ovary syndrome (PCOS), and to evaluate its predictive value for adverse pregnancy and perinatal outcomes in this population. Design Prospective case-control study. Setting Academic Departments of Obstetrics and Gynaecology in Italy. Population Seventy-three pregnant women with ovulatory PCOS (PCOS group) and 73 age- and body mass index-matched healthy pregnant controls (control group). Methods Serial Doppler velocimetry measurements of the uterine artery. Main outcome measures Blood flow impedance indices and pregnancy/perinatal outcomes. Results A significantly (P

Summary Background The intensive physical activity is often associated with cardiac changes. Objectives (i) To evaluate the IGF-I system and myocardial structure and function by standard Doppler echocardiography and Tissue Doppler in athletes and sedentary controls; and (ii) to determine any relationship between IGF-I system and echocardiographic parameters. Methods Nineteen male top-level rowers and 19 age-matched healthy sedentary male controls underwent blood determination of fasting serum IGF-I, IGFBP-3 and acid-labile subunit levels and standard Doppler echocardiography combined with pulsed Tissue Doppler of posterior septal wall, left ventricular (LV) lateral mitral annulus and right ventricular (RV) tricuspid annulus. Myocardial presystolic (PSm), systolic (Sm), the ratio of early diastolic (Em) to atrial (Am) velocities as well as myocardial time intervals were calculated. Results Rowers had higher serum IGF-I levels (P = 0·04), higher biventricular cavity dimensions and wall thicknesses compared to controls. They also had better LV and RV myocardial function than controls. In the rowers, IGF-I was associated with LV ejection fraction (r = 0·50, P = 0·03), RV PSm velocity (r = 0·55, P = 0·01) and with RV myocardial precontraction time (r = −0·57, P = 0·01). These associations remained significant after adjusting for age and heart rate. Conclusions Top-level athletes showed higher IGF-I levels and a better myocardial performance than controls, particularly for the RV systolic activity. The independent correlations between IGF-I and systolic parameters of the left (ejection fraction) and right (PSm velocity and precontraction time) ventricles may possibly indicate a role of IGF-I system in the modulation of myocardial inotropism in athletes. Further studies are needed to confirm this hypothesis.

Summary Objective Heart rate recovery (HRR) is a measure derived from exercise test, defined as the fall in heart rate during the first minute after maximal exercise. Abnormal HRR is a measure of autonomic dysfunction associated with an increased mortality. This study was performed to evaluate the HRR in polycystic ovary syndrome (PCOS). Design Prospective controlled clinical study. Patients Seventy-five PCOS women compared to 75 healthy women matched for age (21·7 ± 2·1 years vs. 21·9 ± 1·8 years, respectively) and body mass index (BMI) (29·0 ± 2·6 kg/m2 vs. 29·1 ± 2·9 kg/m2, respectively). Measurements Subjects were studied for their hormonal and metabolic profile, and underwent cardiopulmonary exercise test (CPX). Results PCOS women showed a significantly reduced HRR (12·9 ± 1·8 vs. 20·4 ± 3·1 beats/min, P

Metformin is an insulin sensitizer currently used for treating type-2 diabetes mellitus and recently administered for inducing ovulatory menstrual cycles in oligo-amenorrhoeic patients with polycystic ovary syndrome (PCOS). The aim of the present review is to describe the efficacy of metformin as an ovulation inducer on the basis of the most important evidence-based medicine supported data, including meta-analyses and randomized controlled trials. Specifically, we reviewed the uses of metformin as first- and second-step treatment for PCOS related anovulatory infertility and as co-treatment in infertile PCOS patients who receive gonadotrophins. To date, there is evidence that metformin is effective for restoring normal menstrual cycles in anovulatory PCOS patients, and that it is more effective and cheaper than laparoscopic ovarian drilling as the second therapeutic step in PCOS patients previously defined as resistant to clomiphene citrate. Co-administration of metformin in PCOS patients treated with gonadotrophin improves the mono-ovulation rate and can prevent ovarian hyperstimulation syndrome in patients treated with gonadotrophins for IVF cycles.

Low 25(OH) vitamin D levels have been associated with several autoimmune diseases and recently with autoimmune thyroid disease (AITD). The aim of the study was to investigate the association of AITD with 25(OH) vitamin D levels in women with polycystic ovary syndrome (PCOS). Fifty women with PCOS were consecutively enrolled and underwent routine health checkups, which included measurements of 25(OH) vitamin D, anti-thyroid peroxidase (TPO-Ab), anti-thyreoglobulin (TG-Ab) antibodies, FT3, FT4, and TSH. Selecting 50 nmol/L as cut-off point, low 25(OH) vitamin D levels were detected in 23 of 50 patients (46 %). AITD was diagnosed when TPO-Ab levels exceeding 80 U/ml and/or TG-Ab levels exceeding 70 U/ml. AITD was detected in 12 of 50 patients (24 %). The levels of 25(OH) vitamin D were significantly lower in women with PCOS and AITD when compared with women with PCOS and without AITD (p = 0.02). In women with AITD no correlation was found between 25(OH) vitamin D and TG-Ab (r = 0.48; p = 0.16), TPO-Ab (r = 0.43; p = 0.21), TSH (r = 0.38; p = 0.27), FT3 (r = -0.40; p = 0.25) and FT4 levels (r = -0.54; p = 0.10). These findings suggest that low levels of 25(OH) vitamin D were significantly associated with AITD in women with PCOS.

Reproductive alterations are a mainstay of the classic definition of polycystic ovary syndrome (PCOS), as defined in 1992 by the NIH consensus statement on PCOS [1]. These abnormalities still represent one of the three cardinal aspects used for diagnosing PCOS according to the current criteria, as defined by the Rotterdam ESHRE/ASRM consensus workshop [2] and by the AE-PCOS Society [3]. In addition, the reproductive alterations of PCOS are a key point in the treatment of this condition. Although there are several guidelines on the management of infertility in PCOS women, this issue remains controversial. Moreover, most of the documents on this topic were produced, by both the human reproduction societies and the endocrinology societies, with pregnancy as an immediate objective. However, reproductive abnormalities are frequently a central problem in these women beyond this specific aim, and come before and after this goal. Physicians are thus called to manage the reproductive alterations of PCOS women also when a pregnancy is not on the program, while taking into account comprehensively the whole spectrum of clinical problems of these patients. This concept is especially important for endocrinologists, who need to manage the many problems of these women for long periods, ideally for all of their lives. With the objective of reviewing the literature on the treatment of the reproductive alterations of PCOS, and developing evidence-based guidelines aimed at improving the management of these abnormalities, The Italian Society of Endocrinology (SIE) Board appointed a panel of experts, selected from researchers who published relevant articles in the field. The project and panel composition was also steered by the conviction that the clinical issues of PCOS should be managed with a network-oriented approach, primarily through strict interaction between endocrinologists and gynecologists.

Background & aims: Nutrition is the major environmental factor that influences the risk of developing pathologies, such as obesity. Although a number of recent reviews pinpoint a protective effects of milk on body weight and obesity related co-morbidities, an inaccurate estimate of milk might contribute to hamper its beneficial effects on health outcomes. Seven-day food records provide prospective food intake data, reducing recall bias and providing extra details about specific food items. Milk intake stimulates the somatotropic axis at multiple levels by increasing both growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. On the other hand, obesity is associated with reduced spontaneous and stimulated GH secretion and basal IGF-1 levels. Aim of this study was to evaluate the milk consumption by using the 7-days food record in obese individuals and to investigate the association between milk intake and GH secretory status in these subjects. Methods: Cross-sectional observational study carried out on 281 adult individuals (200 women and 81 men, aged 18–74 years) with moderate-severe obesity (BMI 35.2–69.4 kg/m2). Baseline milk intake data were collected using a 7 day food record. Anthropometric measurements and biochemical profile were determined. The GH/IGF-1 axis was evaluated by peak GH response after GHRH + ARGININE and IGF-1 standard deviation score (SDS). Results: The majority of individuals (72.2%) reported consuming milk; 250 mL low-fat milk was the most frequently serving of milk consumed, while no subjects reported to consume whole milk. Milk consumers vs no milk consumers presented the better anthropometric measurements and metabolic profile. At the bivariate proportional odds ratio model, after adjusting for BMI, age and gender, milk consumption was associated the better GH status (OR = 0.60; p < 0.001). Among milk consumers, subjects consuming 250 mL reduced-fat milk vs 250 mL low-fat milk presented the better anthropometric measurements and metabolic profile. At the bivariate proportional odds ratio model, after adjusting for BMI, age and gender, the consume of 250 mL reduced-fat milk was associated better GH status (OR = 0.54; p = 0.003).Conclusions: A novel positive association between milk consumption, GH status, and metabolic profile in obese individuals was evidenced. Regardless of the pathogenetic mechanisms, this novel association might be relevant in a context where commonly obese individuals skip breakfast, and suggests the need of a growing cooperation between Nutritionists and Endocrinologists in the management of the obese patients.

Adrenal incidentalomas (AIs) and polycystic ovary syndrome (PCOS) have often been associated with compensatory hyperinsulinemia and insulin resistance (IR). The link between these diseases and IR may be changes in hormone secretions that provoke IR and in turn promote the growth of adrenal gland masses and/or ovarian cysts through compensatory hyperinsulinemia.

Context: Polycystic ovary syndrome (PCOS) is associated with early impairment of vascular structure and a low-grade chronic inflammation. Aldosterone is a well-recognized cardiovascular risk (CVR) factor and is related to inflammatory processes. Objective: Our objective was to investigate serum aldosterone levels in PCOS and correlate them to some CVR factors and early atherosclerotic markers. Design and Setting: A prospective baseline-controlled clinical study was conducted at the University “Federico II” of Naples School of Medicine (Naples, Italy). Patients: Fifty PCOS women age- and body mass index-matched with 50 healthy women were enrolled. Mean Outcome Measures: Anthropometric, hormonal, and metabolic patterns, including plasma aldosterone, renin, and C-reactive protein, were measured in each subject. Intima-media thickness was also evaluated in each patient and control. Results: Aldosterone levels were significantly increased (P < 0.001) in PCOS compared with healthy women (10.5 ± 3.2 vs. 5.7 ± 2.5 ng/dl). In PCOS, a significant (P < 0.001) direct correlation between plasma aldosterone and homeostasis model assessment, C-reactive protein, intima-media thickness, and mean blood pressure was found. On the other hand, high-density lipoprotein cholesterol and potassium were inversely (P < 0.001) related to serum aldosterone. Multiple linear regression analysis showed that the area under the curve for insulin and homeostasis model assessment was linearly related to aldosterone in PCOS. Conclusion: PCOS women show an insulin resistance related increase in serum aldosterone levels.

Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy. Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated. Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. Mean outcome measures: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates. Results: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001). Conclusions: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.

To evaluate the cardiovascular risk of polycystic ovary syndrome (PCOS), we investigated lipid profile, metabolic pattern, and echocardiography in 30 young women with PCOS and 30 healthy age- and body mass index (BMI)-matched women. PCOS women had higher fasting glucose and insulin levels, homeostasis model assessment score of insulin sensitivity, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, and TC/high density lipoprotein cholesterol (HDL-C) ratio and lower HDL-C levels than controls. Additionally, PCOS women had higher left atrium size (32.0 +/- 4.9 vs. 27.4 +/- 2.1 mm; P < 0.0001) and left ventricular mass index (80.5 +/- 18.1 vs. 56.1 +/- 5.4 g/m(2); P < 0.0001) and lower left ventricular ejection fraction (64.4 +/- 4.1 vs. 67.1 +/- 2.6%; P = 0.003) and early to late mitral flow velocity ratio (1.6 +/- 0.4 vs. 2.1 +/- 0.2; P < 0.0001) than controls. When patients and controls were grouped according to BMI [normal weight (BMI, >18 and 30 kg/m(2))], the differences between PCOS women and controls were maintained in overweight and obese women. In normal weight PCOS women, a significant increase in left ventricular mass index and a decrease in diastolic filling were observed, notwithstanding no change in TC, LDL-C, HDL-C, TC/HDL-C ratio, and TG compared with controls. In conclusion, our data show the detrimental effect of PCOS on the cardiovascular system even in young women asymptomatic for cardiac disease.

Objective: To evaluate the safety and efficacy of the administration of low doses of glucocorticoids in patients with cystic fibrosis (CF) by using autologous erythrocytes loaded with dexamethasone 21-phosphate. Study design: Nine consecutive CF patients (patients nos. 1–9) received autologous erythrocytes loaded with increasing amounts of dexamethasone 21-phosphate to obtain a slow delivery of dexamethasone in circulation. The appearance of possible adverse effects, the reproducibility of the procedure, and the dexamethasone pharmacokinetics were evaluated. Subsequently, patient no. 9 and eight additional patients (patient nos. 10–17) received dexamethasone 21-phosphate-loaded erythrocytes at 1-month intervals to evaluate the efficacy of continuous release in circulation of low doses of dexamethasone. Results: Erythrocytes from CF patients can be processed to be loaded with increasing dexamethasone 21-P concentrations. Once reinfused in respective donors, a slow and prolonged delivery of dexamethasone in the blood stream was measured up to 28 days. Repeated administrations of drug-loaded erythrocytes at 4-week intervals for 15 months showed that very low doses of glucocorticoids provide significant improvement in FEV1 values and significant reduction of infective relapses due to Pseudomonas aeruginosa without adverse effects. Conclusions: The administration of very low doses of glucocorticoids using autologous erythrocytes is possible, with benefits for patients and without side effects. This method is likely to be extended to other chronic diseases.

BACKGROUND: Renal transplantation (RT) is the most common solid organ transplant procedure. Several studies have reported on gonadal function in male and female RT recipients with controversial results. METHODS: Forty consecutive patients (20 male, 20 female) with a fully functioning allograft (serum creatinine 0.8-1.3 mg/dl) for at least 15 months after RT were included in the study. Their ages ranged from 23 to 44 years (median 38) and their post-RT follow-up lasted 15-86 months (median 23). FSH, LH, prolactin, 17-beta-estradiol, testosterone, androstenedione and dehydroepiandrostrone were determined in all patients and compared with a group of 80 healthy subjects. Pelvic ultrasonography was performed in all participants. RESULTS: Testosterone was below the normal range in 70% of male patients and within the lowest third in the remainder; a lack of LH increase indicated an inhibition of the reproductive axis. Male testosterone values were negatively influenced by calcineurine inhibitors treatment (P < 0.005), but positively influenced by a better graft function (P < 0.0001). Testicular and prostate volumes were reduced with respect to controls, with the latter related to circulating testosterone levels. Ten of the women (50%) had menstrual cycle disorders after RT, three being affected by transient, and three by persistent, amenorrhea. Another two patients had had transient polymenorrhea. In four women (20%), a premature ovarian failure was diagnosed. No relationship was found between female reproductive function and age, graft function or duration of the post-transplant period. Prolactin was lower in patients on calcineurin inhibitors (P < 0.01). CONCLUSIONS: Abnormalities of the reproductive system were frequent after successful RT in both genders.

Background and Aim: To evaluate the prevalence of goitre by means of urinary iodine excretion, palpatory and ultrasonographic thyroid examinations in a heterogeneous population living by the sea. Methods and Results: We used a special self-administered questionnaire to evaluate thyroid size, iodine intake, eating habits and cardiovascular risk factors in 600 subjects with a mean age of 45±17 years: 253 men (42.3%) and 347 women (57.7%). Urinary iodine excretion was low (72.1±15.7 μg/L; median 71.2) and associated with ultrasonographic evidence of an enlarged thyroid (16%) or structural thyroid abnormalities (30%), thus allowing us to define the Salerno Gulf as a mild-moderate area of endemic goitre. All of the subjects ate a Mediterranean diet, with a mean of two portions of fish/week. The cardiovascular risk factors considered were obesity, cigarette smoking, hypertension, hypercholesterolemia, hypertriglyceridemia and diabetes, the prevalences of which were in line with those reported in other studies of similar age-matched populations. Conclusions: The moderate intake of fish and the consumption of a Mediterranean diet did not prevent goitre. Iodine deficiency and subsequent goitre endemia are also present at sea level, probably because of a diet based on local products grown on soil with a low iodine content or possible seawater, soil and air environmental pollution that may interfere with the availability of iodine. The assessment of iodine deficiency should therefore involve the entire population and not only subjects living far from the sea.

BACKGROUND: Although GnRH analogues are widely used to treat a variety of sex hormone-related diseases, little is known about their effect on metabolism. Therefore, we have evaluated the effect of a GnRH analogue, administered with or without raloxifene, on serum levels of lipoproteins, glucose, insulin and homocysteine (Hcy). METHODS: One hundred premenopausal women with symptomatic uterine leiomyomas were initially enrolled and randomized to receive 3.75 mg/28 days leuprolide acetate depot associated with 60 mg/day raloxifene hydrochloride (group A) or 1 placebo tablet/day (group B) for six cycles of 28 days. At entry and at cycle 6, subjects underwent anthropometric measurements, including body mass index and waist-to-hip ratio measurements, and blood chemistry assays for serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, Hcy, vitamin B(12) and folate concentrations. Insulin resistance was evaluated with the homeostasis model assessment (HOMA) score. RESULTS: Baseline parameters were similar in the two groups. At cycle 6, TC, HDL-C, LDL-C and TG levels were significantly increased (P < 0.05) in group B. In group A, LDL-C levels were unchanged, and TC, HDL-C and TG levels were increased (P < 0.05). Serum TC and LDL-C levels differed (P < 0.05) between the groups. Glucose levels were unchanged between and within groups, whereas insulin levels and HOMA scores increased (P < 0.05) versus baseline in group B. Post-treatment Hcy levels were higher (P < 0.05) versus baseline in group B; they were unchanged in group A. Serum vitamin B(12) and folate concentrations were unchanged in both groups. CONCLUSIONS: GnRH analogues alter serum lipoprotein and Hcy levels and increase insulin resistance. These acute metabolic changes may be prevented or reduced by raloxifene.

This work was designed to determine whether IGF-1 and EGF modulate nuclear transfer and transactivation of the androgen receptor (AR) in human prostate cell lines (PNT1A and DU-145). We first characterized the IGF-1 and EGF receptors by ligand-binding assays with [125I] IGF-1 and [125I] EGF in a normal human prostate epithelial cell line, PNT1A. We then evaluated the effects of these growth factors on AR nuclear transfer and transcriptional activation in this cell line and in DU-145, a human prostate tumor cell line. The cell lines were cotransfected with an AR expression vector and an androgen-responsive luciferase gene driven by the mouse mammary tumor virus (MMTV-luciferase) promoter. Neither IGF-1 nor EGF could activate reporter gene in the absence of androgens. Conversely, both enhanced the magnitude of the AR response in the presence of low levels of androgen (10−11–10−9 M) and this response, increased by twofold, was inhibited by hydroxyflutamide. No effect of IGF-1 and EGF was observed on the intracellular localization of the fusion protein EGFP-AR in either cell line. The fluorescence stayed cytoplasmic even after 24 h of IGF-1 or EGF treatment. Taken together, these data indicate that growth factors are unable to initiate the nuclear translocation of AR in the absence of androgens or to induce ligand-independent transcriptional activity. We observed only cross-talk in the presence of androgens and IGF-1 or EGF, leading to an over-activated AR. In conclusion, the cross-talk between AR and growth factor signaling pathways may sensitize AR to suboptimal stimulation by low levels of androgens.

Vitamin D (25(OH)D) levels have been associated with cardiovascular disease. Thus, the aim of our study was to investigate the association of 25(OH)D levels with coronary heart disease (CHD) in 698 consecutive type 2 diabetic outpatients. 698 consecutive type 2 diabetic outpatients (25.2 % men, age 66 ± 9 years) and 100 (90 % men, age 65 ± 13 years) age-matched non-diabetic volunteers were enrolled. 25(OH)D assay and the main cardiovascular risk factors were explored. 25(OH)D concentration was 22 ± 10 ng/ml in control subjects and 18.23 ± 10 ng/ml in diabetic patients (p < 0.01). The prevalence of hypovitaminosis D was higher in diabetic patients than in control subjects (90 vs. 83 %, p < 0.01). Diabetic subjects with hypovitaminosis D had higher prevalence of high values of A1C (p < 0.01), BMI (p < 0.01), LDL cholesterol (p < 0.01), triglycerides (p < 0.01), and glycemia (p < 0.01) than their vitamin D-sufficient counterparts. 25(OH)D and HDL cholesterol were lower (p < 0.01), while BMI (p < 0.01), age (p < 0.01), systolic (p < 0.01) and diastolic blood pressure (p < 0.01), diabetes duration (p < 0.01), A1C (p < 0.01), glycemia (p < 0.01), fibrinogen (p < 0.01), triglycerides (p < 0.01), and total (p < 0.01) and LDL cholesterol (p < 0.01) were higher in diabetic subjects with CHD than diabetic subjects without CHD. At the logistic regression analysis, the association of vitamin D with CHD was lost, while sex (p = 0.026), diabetes duration (p = 0.023), and age (p = 0.024) were the most powerful predictors of CHD. The current study demonstrates that 25(OH)D does not have a direct effect on CHD but may have an indirect effect mediated by cardiovascular risk factors such as diabetes duration, age, and sex.

Aims: Statins are the main lipid-lowering treatment in both primary and secondary prevention populations. Whether statins deteriorates glycemic control, predisposing to the onset of diabetes mellitus has been a matter of recent concern. Statins may accelerate progression to diabetes via molecular mechanisms that impact insulin sensitivity and secretion. In this review, we debate the relative effect of statins in driving insulin resistance and the impairment of insulin secretion. Methods: Narrative overview of the literature synthesizing the findings of literature was retrieved from searches of computerized databases, hand searches, and authoritative texts employing the key words "Statins", "Randomized Clinical Trial", "Insulin sensitivity", "Insulin resistance", "Insulin Secretion", "Diabetes Mellitus" alone and/or in combination. Results: The weight of clinical evidence suggests a worsening effect of statins on insulin resistance and secretion, anyway basic science studies did not find a clear molecular explanation, providing conflicting evidence regarding both the beneficial and the adverse effects of statin therapy on insulin sensitivity. Conclusions: Although most of the clinical studies suggest a worsening of insulin resistance and secretion, the cardiovascular benefits of statin therapy outweigh the risk of developing insulin resistance, thus the data suggest the need to treat dyslipidemia and to make patients aware of the possible risk of developing type 2 diabetes or, if they already are diabetic, of worsening their metabolic control.

Polycystic ovary syndrome (PCOS) and pregnancy are conditions characterized by an increased low-grade chronic inflammation state. A higher incidence of pregnancy complications has been detected in pregnant PCOS women.The objective of the study was to test the hypothesis that the low-grade chronic inflammation state typical of PCOS patients persists during gestation and is exacerbated by pregnancy and contributes to the increased risk of obstetric/neonatal complications.This was a prospective controlled clinical study.The study was conducted at the Academic Department of Obstetrics and Gynecology of the "Pugliese-Ciaccio" Hospital of Catanzaro (Catanzaro, Italy).One hundred fifty pregnant PCOS women and 150 age- and body mass index-matched healthy pregnant controls participated in the study.INTERVENTIONS included serial clinical, biochemical, and ultrasonographic assessments before and throughout pregnancy.Serum levels of white blood cell count (WBC), C-reactive protein (CRP), and ferritin were measured.Pregnant women with PCOS had higher WBC, CRP, and ferritin levels at study entry and at all gestational ages than controls. Changes in serum WBC and ferritin levels were significantly higher in PCOS than in controls starting from the 12th week of gestation whereas those in CRP from the 20th week of gestation. By multivariable Cox proportional hazard analysis, in the PCOS group, a significant association with the risk of adverse obstetric/neonatal outcomes was found for WBC [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.31-1.64; P = .010], CRP (HR 1.19, 95% CI 1.06-1.34; P = .019), and ferritin levels (HR 1.12, 95% CI 1.03-1.26; P = .011).In PCOS patients, the low-grade chronic inflammation persists during gestation and is exacerbated by pregnancy, and it is associated with adverse pregnancy outcomes.