Long term mortality and morbidity of Italian soldiers after deployment in Iraq as related to biomarkers assessment: Results of the SIGNUM study.

INTRODUCTION: The health profile of military veterans deployed in foreign operative theatres was assessed by several international studies because of potential exposure to depleted uranium and other pollutants. Here we reported results of 15-year epidemiological surveillance assessing long-term health effects in a cohort of Italian soldiers deployed in Iraq in 2004-2005 and participating in a biomonitoring campaign to identify potential genotoxic exposure to environmental xenobiotics before and after deployment (n = 981, SIGNUM cohort). METHODS: We evaluated mortality and hospitalization risks of the SIGNUM cohort retrospectively until 2016 and 2018 respectively. A wide cohort of military personnel never deployed abroad (n = 114,260) and the general Italian population were used as control populations in risk assessment. Causes of death and diagnoses of hospitalization were derived through deterministic record linkage with official national databases of mortality and hospital discharge. Standardized Mortality Ratio (SMR) and Standardized Hospitalization Ratio (SHR) were computed adjusting according to sex, age, area of birth, and calendar year. Differential pre-post deployment in xenobiotics concentrations and early effect biomarkers (oxidative DNA alterations and micronuclei) measured in blood serum were analysed in relation to cancer hospitalization. RESULTS: Mortality risk due to pathologies was more than halved compared to the general population (SMR = 0.41, 95% CI 0.11-1.05) and not significantly different compared to soldiers never deployed abroad (SMR = 0.69, 95% CI 0.19-1.68). Similarly overall hospitalization risk due to pathologies was decreased with respect to the general population (SHR = 0.86, 95% CI 0.80-0.92) and comparable to the control military group (SHR = 0.99, 95% CI: 0.93-1.06). For haematological cancers a decreased hospitalization risk compared to the Italian general population was observed (SHR = 0.38, 95% CI 0-0.92). No statistically significant differences emerged in the patterns of biomarkers in association with cancer hospitalization. CONCLUSION: The study confirms the so called 'healthy warrior' effect for the SIGNUM veterans and showed no correlation between cancer occurrence and biomonitoring markers measured on field.

Oral contraceptives versus physical exercise on cardiovascular and metabolic risk factors in women with polycystic ovary syndrome: a randomized controlled trial.

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 µg ethinyloestradiol), structured exercise training programme (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. Oral contraceptives 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.

Sensitive method for measuring third order nonlinearities in compact dielectric and hybrid plasmonic waveguides.

We demonstrate a sensitive method for the nonlinear optical characterization of micrometer long waveguides, and apply it to typical silicon-on-insulator nanowires and to hybrid plasmonic waveguides. We demonstrate that our method can detect extremely small nonlinear phase shifts, as low as 7.5·10<(-4) rad. The high sensitivity achieved imparts an advantage when investigating the nonlinear behavior of metallic structures as their short propagation distances complicates the task for conventional methods. Our results constitute the first experimental observation of χ((3)) nonlinearities in the hybrid plasmonic platform and is important to test claims of hybrid plasmonic structures as candidates for efficient nonlinear optical devices.

Three-dimensional atomic-scale structure of size-selected gold nanoclusters.

An unambiguous determination of the three-dimensional structure of nanoparticles is challenging. Electron tomography requires a series of images taken for many different specimen orientations. This approach is ideal for stable and stationary structures. But ultrasmall nanoparticles are intrinsically structurally unstable and may interact with the incident electron beam, constraining the electron beam density that can be used and the duration of the observation. Here we use aberration-corrected scanning transmission electron microscopy, coupled with simple imaging simulation, to determine with atomic resolution the size, three-dimensional shape, orientation and atomic arrangement of size-selected gold nanoclusters that are preformed in the gas phase and soft-landed on an amorphous carbon substrate. The structures of gold nanoclusters containing 3096 atoms can be identified with either Ino-decahedral, cuboctahedral or icosahedral geometries. Comparison with theoretical modelling of the system suggests that the structures are consistent with energetic considerations. The discovery that nanoscale gold particles function as active and selective catalysts for a variety of important chemical reactions has provoked much research interest in recent years. We believe that the detailed structure information we provide will help to unravel the role of these nanoclusters in size- and structure-specific catalytic reactions. We note that the technique will be of use in investigations of other supported ultrasmall metal cluster systems.

Macroscopic and microscopic findings of the placenta in women with polycystic ovary syndrome.

STUDY QUESTION: Do patients with polycystic ovary syndrome (PCOS) have macroscopic and/or microscopic placental alterations? SUMMARY ANSWER: The placental structure in patients with PCOS, even in those with uncomplicated pregnancy, is altered. WHAT IS KNOWN ALREADY: The spectrum of pregnancy complications seems to have a common denominator: a defective trophoblast invasion and placentation. In women with PCOS, alterations in endovascular trophoblast invasion related to insulin resistance and hyperandrogenism have been observed. STUDY DESIGN, SIZE, DURATION: For this prospective case-control study, 30 pregnant patients with PCOS (cases) and 60 healthy pregnant women without PCOS features (controls) were enrolled and studied until delivery. Clinical, biochemical, ultrasonographic and obstetric data were recorded. The baseline clinical and biochemical data for screening for PCOS and for inclusion/exclusion were obtained before the seventh week of gestation. At delivery, placentas were collected and detailed macroscopic and microscopic analyses were performed. PARTICIPANTS, SETTING, METHODS: Cases and controls were matched for age and BMI (all <30 kg/m(2)). The matching procedure was one-to-two. Only subjects with spontaneous conception and uncomplicated pregnancies were included in the final analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Placental weight (P = 0.04), thickness (P = 0.02), density (P = 0.02) and volume (P = 0.01) were significantly inferior in women with, compared with those without PCOS. The placentas from patients with PCOS more frequently had an irregular shape (P = 0.03) and a higher cord coiling index (P = 0.02). Differences between cases and controls also concerned the extent of villous (P = 0.04) and intervillous (P = 0.01) spaces, the extent of fibrosis (P = 0.03), endovascular trophoblast (depth, extension and morphometry) (P < 0.05) and mitotic activity (P = 0.01). The percentage of patients with lesions [22/30 (73.3%) versus 25/60 (41.7%), respectively; P = 0.01] and the mean number of placental lesions (3.5 ± 2.1 versus 1.4 ± 1.1, respectively; P = 0.02) were higher in the PCOS than the control group. The odds ratio for placental alterations, adjusted for weight gain, was 2.8 (95% confidence interval 1.3-9.9). LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study was the selection of a specific PCOS sample, which is probably not representative of the PCOS phenotype as a whole. In fact, we excluded patients with PCOS who were obese and who achieved a pregnancy following the use of ovulation inductors or assisted reproduction techniques. WIDER IMPLICATIONS OF THE FINDINGS: The present study is the first to demonstrate that the morphology and microscopic structure of placenta in patients with PCOS with an uncomplicated pregnancy are altered. Further studies are needed to assess a correlation of these changes with the increased risk of obstetric complications observed in some pregnancies of women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no conflict of interest and no financial support for the research. TRIAL REGISTRATION NUMBER: N/A.

Effects of metformin in women with polycystic ovary syndrome treated with gonadotrophins for in vitro fertilisation and intracytoplasmic sperm injection cycles: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Metformin is widely used for treating women with polycystic ovary syndrome (PCOS), and many patients with PCOS who are infertile receive gonadotrophins while being treated with metformin. OBJECTIVES: To assess the effects of metformin administration in infertile patients with PCOS who receive gonadotrophins for in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cycles. SEARCH STRATEGY: We searched international scientific databases, websites for the registration of trials, and bibliographies of retrieved articles, books, and review articles up to August 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: Authors independently reviewed and extracted the data. MAIN RESULTS: Ten RCTs (with a total of 845 women with PCOS) were included in the final analysis. Metformin administration in IVF/ICSI cycles had no effect on the rates of pregnancy (OR 1.20, 95% CI 0.90-1.61) and live birth (OR 1.69, 95% CI 0.85-3.34). No effect of metformin dose, metformin pretreatment duration, and stopping time of metformin administration was observed on these reproductive end points. Metformin administration reduced the risk of ovarian hyperstimulation syndrome (OHSS; OR 0.27, 95% CI 0.16-0.46) and of miscarriage (OR 0.50, 95% CI 0.30-0.83), while increased that of implantation (OR 1.42, 95% CI 1.24-2.75). AUTHOR'S CONCLUSIONS: In infertile patients with PCOS treated with gonadotrophins for IVF/ICSI cycles, metformin exerts no clinical effect on rates of pregnancy or live birth, but it reduces the risk of OHSS, and improves the rates of miscarriage and implantation. Further RCTs are needed to assess the reproductive effect of metformin in young well-selected patients with PCOS and specific phenotypes and features.

Effects of physical exercise on the female reproductive system.

The excess in physical activity could be closely linked to considerable negative consequences on the whole body. These dysfunctions called as "female athlete triad"' by the American College of Sports Medicine (ACSM) include amenorrhea, osteoporosis and disorder eating. The female athlete triad poses serious health risks, both on the short and on the long term, to the overall well-being of affected individuals. Sustained low energy availability can impair health, causing many medical complications within skeletal, endocrine, cardiovascular, reproductive and central nervous system. On the contrary, several studies have shown, that physical activity improves cardiovascular risk factors, hormonal profile and reproductive function. These improvements include a decrease in abdominal fat, blood glucose, blood lipids and insulin resistance, as well as improvements in menstrual cyclicity, ovulation and fertility, decreases in testosterone levels and Free Androgen Index (FAI) and increases in sex hormone binding globulin (SHBG). Other studies reported that physical activity improved self-esteem, depression and anxiety. Thus, the aim of this review is to elucidate the effect of physical exercise on female reproductive system and viceversa the impact of hormonal status on physical activity and metabolism. In addition this review supports the idea that physical exercise is a helpful tool for the management of obesity, prevention of cardiovascular, metabolic diseases and female reproductive organs related diseases (e.g. breast cancer). When the excess in physical activity leads up to the female athlete triad, it is imperative to treat each component of the triad by employing both pharmacological and non pharmacological treatments.

HPV at the time of vaccine: has screening reached its goal?

INTRODUCTION: The human papillomavirus (HPV) prevalence recognized a geographic distribution of genotypes but, in the last years, the change of sexual behaviours, the increase number of sex partners, and the reduction of geographic distances have changed its prevalence and distribution. OBJECTIVE: To determine the prevalence of HPV types among females in the Molise region and its evolution in 24 months. MATERIALS AND METHODS: The authors, from February to August 2008, used a representative sample of a female population (n = 299) aged 17 to 64 years who were interviewed and submitted cervico-vaginal swab specimens. Swabs were analyzed for cytologic screening and HPV detection and typing. The patients with a positive cytology were submitted to colposcopy and eventually biopsy. Cytological and colposcopic follow up was performed in 24 months. RESULTS: The overall HPV prevalence was 30.1% and the prevalence of high- and low-risk HPV types was 22.41% and 18.06%, respectively. The prevalence of HPV vaccine types was relatively low for HPV-6-11-18. Only HPV-16 is well-represented in Molise, but recognizes a strictly geographic distribution. CONCLUSION: This study is one of the largest assessments of HPV genotypes to date in Italy. It is clear that several HPV-types are involved in cervical lesions, therefore the vaccine is profitable but limited by great number of types implicated in the pathogenesis of cancer and by their dishomogeneous distribution. Currently, a good campaign of screening is still necessary. In the future, second generation polyvalent HPV vaccines my be proposed for a wider and complete vaccine coverage.

Ovarian function and gastrointestinal motor activity.

Gastrointestinal disorders are strictly related to the ovary function. In fact, it is noted that the prevalence of visceral pain disorders such as irritable bowel syndrome, gastroesophageal reflux disease, gallbladder and biliary tract diseases are significantly higher in women. Furthermore, symptom such as nausea, vomiting, abdominal pain, distension, satiety, bloating, diarrhoa or constipation, frequently appears in relation with pregnancy, luteal phase of the menstrual cycle or perimenopausal and menopausal states. Further support for the contribution of ovarian steroids to functional gastrointestinal disorders comes from studies demonstrating that pharmacological ovariectomy reduces abdominal pain symptoms. Therefore, addressing the influence of sex and sex hormones in the modulation of visceral pain appears critical to develop new strategies of diagnosis and therapy sex-directed for gastro-intestinal disorders.

Effects of highly purified follicle-stimulating hormone on sperm DNA damage in men with male idiopathic subfertility: a pilot study.

BACKGROUND: Gonadotropins administration have been demonstrated effective for the treatment of idiopathic male infertility, even if no clear data regarding their specific mechanism of action on semen quality are at the moment available. AIM: To evaluate the effect of highly purified FSH (hpFSH) administration on standard semen parameters, sperm oxidative stress, and sperm chromatin structure and DNA fragmentation. MATERIAL AND METHODS: In the current prospective baseline-controlled study, 36 subjects with male idiophatic infertility were enrolled. Baseline clinical and biochemical data were evaluated. Before and after 3 months of treatment with hpFSH, sperm samples were collected and standard semen analysis, reactive oxygen species (ROS) assessment and sperm DNA fragmentation were evaluated. RESULTS: A significant (p<0.05) improvement from baseline in standard seminal parameters was observed. A significant (p<0.05) reduction in sperm ROS levels and DNA fragmentation was observed. Statistically significant (p<0.05) correlations between variation in ROS levels and both seminal parameters and DNA fragmentation variations were detected. CONCLUSIONS: Three months of hpFSH administration seems to reduce ROS and DNA damage in subjects with male idiopathic subfertility improving semen parameters. Further evidences from well-designed randomized double-blind placebo- controlled studies are needed in order to confirm our preliminary results.

[A retrospective analysis comparing colposuspension and retropubic mid-urethral sling as preventive anti-incontinence measures during laparoscopic sacrocolpopexy]. / Analisi retrospettiva di confronto tra colposospensione e sling retropubica medio-uretrale come misure preventive anti-incontinenza in corso di sacrocolpopessia laparoscopica.

AIM: The aim of this paper was to compare two anti-incontinence procedures during laparoscopic sacrocolpopexy (LSC) to prevent postoperative stress urinary incontinence (SUI). METHODS: Retrospective analysis of 90 continent hysterectomized patients with vaginal vault prolapse treated with LSC plus colposuspension (group A, N.=30), LSC plus retropubic mid-urethral sling (group B, N.=30), or LSC alone (group C, N.=30). RESULTS: De novo SUI rate resulted significantly (P<0.05) lower in group B than C. No difference was detected regarding de novo urge urinary incontinence. Total reoperation rate resulted significantly (P<0.05) higher in group A than B and lower in group B than C. CONCLUSION: When associated to LSC for preventing SUI, colposuspension and retropubic mid-urethral sling are effective and safe, even if mid-urethral sling seems to provide the best risk/benefit profile.

[Sex ratio in the offspring of pregnant women with polycystic ovary syndrome: effect of different phenotypes]. / Sex ratio nella prole di donne affette dalla sindrome dell'ovaio policistico: effetti dei differenti fenotipi.

AIM: The aim of this paper was to investigate the sex ratio in the offspring of pregnant patients with polycystic ovary syndrome (PCOS). METHODS: Analysis of 70 pregnant patients with PCOS who achieve a pregnancy without any kind of treatment, and having as controls 63 healthy pregnant women without any feature of PCOS. RESULTS: No significant difference in sex ratio was detected between PCOS and controls, even if it resulted significantly different in the full-blown and non-PCO phenotypes. CONCLUSION: The PCOS phenotypes influenced the sex ratio in the offspring, suggesting that environmental factors could play a role in determination of the offspring gender.

Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Clomiphene citrate (CC) is the first-line therapy for the induction of ovulation in infertile women with polycystic ovary syndrome (PCOS), but ∼20% of patients are unresponsive. The aim of the current study was to test the hypothesis that a 6-week intervention that consisted of structured exercise training (SET) and hypocaloric diet increases the probability of ovulation after CC in overweight and obese CC-resistant PCOS patients. METHODS: A cohort of 96 overweight and obese CC-resistant PCOS patients was enrolled consecutively in a three-arm randomized, parallel, controlled, assessor-blinded clinical trial. The three interventions were: SET plus hypocaloric diet for 6 weeks (Group A); 2 weeks of observation followed by one cycle of CC therapy (Group B); and SET plus hypocaloric diet for 6 weeks, with one cycle of CC after the first 2 weeks (Group C). The primary end-point was the ovulation rate. Other reproductive data, as well as anthropometric, hormonal and metabolic data, were also collected and considered as secondary end points. RESULTS: After 6 weeks of SET plus hypocaloric diet, the ovulation rate was significantly (P =0.008) higher in Group C [12/32 (37.5%)] than in Groups A [4/32 (12.5%)] and B [3/32 (9.4%)] with relative risks of 3.9 [95% confidence interval (CI) 1.1-8.3; P = 0.035] and 4.0 (95% CI 1.2-12.8; P = 0.020) compared with Groups A and B, respectively. Compared with baseline, in Groups A and C, a significant improvement in clinical and biochemical androgen and insulin sensitivity indexes was observed. In the same two groups, the insulin sensitivity index was significantly (P < 0.05) better than that in Group B. CONCLUSIONS: In overweight and obese CC-resistant PCOS patients, a 6-week intervention of SET and a hypocaloric diet was effective in increasing the probability of ovulation under CC treatment. The study was registered at Clinicaltrials.gov:NCT0100468.

Uterine blood flow in pregnant patients with polycystic ovary syndrome: relationships with clinical outcomes.

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 < 0.05) higher rate of subjects with abnormal velocimetry findings was observed in the PCOS group than in the control group. In the PCOS group, the pulsatility index (PI) at first (P = 0.042) and mid-second (P = 0.039) trimesters of pregnancy, and bilateral notch at first (P = 0.025) and mid-second (P = 0.007) trimesters of pregnancy, were the strongest independent predictors of adverse outcomes. Conversely, in the control group, PI at the first trimester of pregnancy was a predictor of adverse outcomes only when combined with bilateral notch (P = 0.042), whereas at mid-second trimester of pregnancy PI (P = 0.033) and bilateral notch (P = 0.048) were independent predictors of adverse outcomes. CONCLUSIONS: Uterine artery Doppler indices are more commonly altered in pregnant patients with PCOS than in controls, showing a high predictive value for abnormal pregnancy/perinatal outcomes.

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62 MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter.

PURPOSE: The purpose of this study was to investigate for the first time the performance of a synthetic single crystal diamond detector for the microdosimetric characterization of clinical 62 MeV ocular therapy proton beams. METHODS: A novel diamond microdosimeter with a well-defined sensitive volume was fabricated and tested with a monoenergetic and spread-out Bragg peak (SOBP) of the CATANA therapeutic proton beam in Catania, Italy. The whole sensitive volume of the detector has an active planar-sectional area of 100 µm × 100 µm and a thickness of approximately 6.3 um. Microdosimetric measurements were performed at several water equivalent depths, corresponding to positions of clinical relevance. From the measured spectra, microdosimetric quantities such as the frequency mean lineal energy ( y ¯ F ), dose mean lineal energy ( y ¯ D ) as well as microdosimetric relative biological effectiveness (RBEµ ) values were derived for each depth along both a pristine Bragg curve and SOBP. Finally, Geant4 Monte Carlo simulations were performed modeling the detector geometry and CATANA beamline in order to calculate the average linear energy transfer (LET) values in the diamond active layer and water. RESULTS: The microdosimetric spectra acquired by the diamond microdosimeter show different shapes as a function of the water equivalent depths. No spectral distortion, due to pile-up events and polarization effects, was observed. The experimental spectra have a very low detection threshold due to the electronic noise during the irradiation of about 1 keV/µm. The y ¯ F and y ¯ D values were in agreement with expected trends, showing a sharp increase in mean lineal energy at the distal edge of the Bragg peak. In addition, a good agreement between the mean lineal energy values and the calculated average LET ones was also observed. Finally, the RBE values evaluated with the diamond microdosimeter were in excellent agreement with those obtained with a mini tissue equivalent proportional counter as well as with radiobiological measurements in the same proton beam field. CONCLUSIONS: The microdosimetric performance of the tested synthetic single crystal diamond microdosimeter clearly indicates its suitability for quality assurance in clinical proton therapy beam.

Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study.

BACKGROUND: Lifestyle modifications are successfully employed to treat obese and overweight women with polycystic ovary syndrome (PCOS). The aims of the current pilot study were (i) to compare the efficacy on reproductive functions of a structured exercise training (SET) programme with a diet programme in obese PCOS patients and (ii) to study their clinical, hormonal and metabolic effects to elucidate potentially different mechanisms of action. METHODS: Forty obese PCOS patients with anovulatory infertility underwent a SET programme (SET group, n = 20) and a hypocaloric hyperproteic diet (diet group, n = 20). Clinical, hormonal and metabolic data were assessed at baseline, and at 12- and 24-week follow-ups. Primary endpoint was cumulative pregnancy rate. RESULTS: The two groups had similar demographic, anthropometric and biochemical parameters. After intervention, a significant improvement in menstrual cycles and fertility was noted in both groups, with no differences between groups. The frequency of menses and the ovulation rate were significantly (P < 0.05) higher in the SET group than in diet group but the increased cumulative pregnancy rate was not significant. Body weight, body mass index, waist circumference, insulin resistance indexes and serum levels of sex hormone-binding globulin, androstenedione and dehydroepiandrosterone sulphate changed significantly (P < 0.05) from baseline and were significantly different (P < 0.05) between the two groups. CONCLUSIONS: Both SET and diet interventions improve fertility in obese PCOS patients with anovulatory infertility. We hypothesize that in both interventions an improvement in insulin sensitivity is the pivotal factor involved in the restoration of ovarian function but potentially acting through different mechanisms.

Metabolic and cardiovascular consequences of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5-10% of reproductive aged women, about 1 out of 15 women worldwide. Traditionally it was considered as a reproductive disorder showing hyperandrogenism, chronic anovulation and infertility; it is now well accepted that PCOS represents a ''multifaceted'' syndrome with substantial metabolic and cardiovascular long term consequences. Several PCOS women present abdominal adiposity (visceral fat) with a level of peripheral insulin resistance (IR), similar to that present in women with type 2 diabetes, in association with an increased incidence of impaired glucose tolerance. Several cardiovascular risk factors are often related to metabolic alterations, such as dyslipidemia, hypertension, endothelial dysfunction, low grade chronic inflammation, that are present even at early age in PCOS women. Pathogenetic mechanisms of these impairments are not completely clarified yet, but IR appears to play a critical role, such as the key factor linking hypertension, glucose intolerance, obesity, lipid abnormalities and coronary artery disease. In conclusion, although increased incidence of metabolic abnormalities and metabolic disease like type 2 diabetes, and several cardiovascular abnormalities have been widely demonstrated in PCOS women, larger and multicenter trials of long term cardiovascular outcomes are required to better define the incidence of cardiovascular risk and cardiovascular disease in PCOS.

Role of metformin in patients with polycystic ovary syndrome: the state of the art.

Metformin, an insulin sensitizer widely used for the treatment of patients with type-2 diabetes mellitus (DM), was recently introduced in the clinical practice to treat women with polycystic ovary syndrome (PCOS). The aim of the current review was to evaluate the current role of metformin in the treatment of the PCOS-related disorders. The Authors analyze here the administration of metformin for treating the ovarian dysfunction due to PCOS, and show the evidences available in literature regarding its alternative uses.

[Sjögren's syndrome extraglandular expressions]. / Manifestazioni extraghiandolari della sindrome di Sjogren: implicazioni in ginecologia e ostetricia.

The Sjögren's syndrome (SS) is an autoimmune disease which causes injury to lacrimal and salivar glands and is characterized by a potential systemic involvement. The present review will treat mainly of SS extraglandular expressions, focusing on scientific literature articles regarding SS implications in gynecology and obstetrics.