Endocrine Disorders and COVID-19.

The multifaceted interaction between coronavirus disease 2019 (COVID-19) and the endocrine system has been a major area of scientific research over the past two years. While common endocrine/metabolic disorders such as obesity and diabetes have been recognized among significant risk factors for COVID-19 severity, several endocrine organs were identified to be targeted by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). New-onset endocrine disorders related to COVID-19 were reported while long-term effects, if any, are yet to be determined. Meanwhile, the "stay home" measures during the pandemic caused interruption in the care of patients with pre-existing endocrine disorders and may have impeded the diagnosis and treatment of new ones. This review aims to outline this complex interaction between COVID-19 and endocrine disorders by synthesizing the current scientific knowledge obtained from clinical and pathophysiological studies, and to emphasize considerations for future research.

The role of systemic immune inflammatory index in showing active lesion in patients with multiple sclerosis : SII and other inflamatuar biomarker in radiological active multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) has two pathophysiological processes, one inflammatory and the other degenerative. We investigated the relationship between active lesions on magnetic resonance imaging showing the inflammatory phase in MS patients and serum parameters that can be used as inflammatory biomarkers. Thus, we aim to detect the inflammatory period in clinical and radiological follow-up and to reveal the period in which disease-modifying treatments are effective with serum parameters. METHODS: One hundred eighty-six MS patients presented to our hospital between January 2016 and November 2021 and 94 age- and sex-matched healthy volunteers were recruited for our study. While 99 patients had active lesions on magnetic resonance imaging, 87 patients did not have any active lesions. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) were determined. The SII (systemic immune inflammatory index) value was calculated according to the platelet X neutrophil/lymphocyte ratio formula. RESULTS: NLR, MLR, PLR and SII values were found to be statistically significantly higher in MS patients than in the control group. The NLR, MLR, PLR and SII were higher in the active group with gadolonium than in the group without active lesions. In addition, the cutoff values that we can use to determine the presence of active lesions were 1.53, 0.18, 117.15, and 434.45 for NLR, MLR PLR and SII, respectively. CONCLUSIONS: We found that all parameters correlated with radiological activity. In addition, we showed that we can detect the inflammatory period with high sensitivity and specificity with the cutoff value used for SII and PLR. Among these easily accessible and inexpensive evaluations, we concluded that SII, including the values in the PLR formula, can come to the fore.

The impact of ageing and menopause in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common hormonal, metabolic and reproductive disorder. Women with PCOS at reproductive age have increased risk and prevalence of prediabetes and diabetes and have multiple risk factors for cardiometabolic disease and other comorbidities such as obstructive sleep apnoea, endometrial cancer and mood disorders, which contribute to the overall health burden of the syndrome. However, little is known about the impact of PCOS on long-term health in ageing women. In this review, we aimed to give an updated overview regarding the long-term health outcomes of PCOS and their clinical implications in peri- and postmenopause. The PCOS phenotype ameliorates with ageing and limited available data suggest that there is no further deterioration in cardiometabolic profile in women with PCOS after menopause. Accordingly, the risk of cardiovascular disease in ageing women with PCOS seems to be no different from those without PCOS and lower than previously anticipated based on their risk during reproductive years. Regarding other comorbidities including sleep apnoea, mood disorders and endometrial cancer, it is difficult to determine the true risk in older women with PCOS due to the confounding factors and lack of long-term cohort studies. Large, prospective studies on community-based and well-phenotyped PCOS cohorts with extended follow-up into late menopause are needed to confirm these findings.

Aging versus youth: Endocrine aspects of vulnerability for COVID-19.

Coronavirus Disease 2019 (COVID-19) is characterized with a wide range of clinical presentations from asymptomatic to severe disease. In patients with severe disease, the main causes of mortality have been acute respiratory distress syndrome, cytokine storm and thrombotic events. Although all factors that may be associated with disease severity are not yet clear, older age remains a leading risk factor. While age-related immune changes may be at the bottom of severe course of COVID-19, age-related hormonal changes have considerable importance due to their interactions with these immune alterations, and also with endothelial dysfunction and comorbid cardiometabolic disorders. This review aims to provide the current scientific evidence on the pathogenetic mechanisms underlying the pathway to severe COVID-19, from a collaborative perspective of age-related immune and hormonal changes together, in accordance with the clinical knowledge acquired thus far.

Investigation of taste function and eating behavior in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age that is associated with eating disorders and disordered eating. No data is available regarding taste function in women with PCOS. The aim of this study was to assess taste function and eating behavior in patients with PCOS compared to healthy women and investigate potential impact of oral contraceptive (OC) use on those. Forty-four patients with PCOS and 36 age and body-mass-index matched healthy controls were enrolled. Gustatory function was assessed by taste strips (sweet, sour, salty, bitter) and Food Cravings Questionnaire-Trait (FCQ-T), Night Eating Questionnaire (NEQ) and Three Factor Eating Questionnaire-R18 (TFEQ-R18) were applied. All measurements were repeated in patients after receiving an OC along with general lifestyle advice for 3 months. At baseline, PCOS group had lower total taste strip test (TST) scores compared to controls (11.7 ± 2.2 vs. 13.1 ± 1.4; p = 0.001). Subgroup analysis showed lower sour and salty taste scores in PCOS group (2.4 ± 0.9 vs. 2.9 ± 0.7; p = 0.004; and 2.6 ± 1 vs. 3.1 ± 0.7; p = 0.01 respectively). Sweet and bitter taste scores were similar. No difference was determined in eating behavior. Linear regression analysis revealed that hyperandrogenism was significant predictor for total TST score (R2 = 0.22, p < 0.001). Higher free androgen index (FAI) was associated with lower total TST score (p = 0.01). Total TST score, TFEQ-R18 and NEQ scores remained unaltered after treatment in the PCOS group whereas FCQ-T scores showed significant reduction (p = 0.02), mainly due to a decrease in lack of control subscale (p = 0.01). Our results suggest that taste perception is reduced in PCOS, and short-term OC use does not alter taste functions in the syndrome.

Impact of social isolation during COVID-19 pandemic on health behaviors and weight management in women with polycystic ovary syndrome.

PURPOSE: COVID-19 pandemic has far-reaching psychosocial implications for chronic health conditions. We aimed to investigate whether COVID-19 associated social isolation affects lifestyle and weight control in women with polycystic ovary syndrome (PCOS). METHODS: We conducted an online survey involving 232 women with PCOS and 157 healthy controls on weight changes, physical activity, sleep and eating patterns using Three-Factor Eating Questionnaire (TFEQ-18), Pittsburgh Sleep Quality Index (PSQI), and International Physical Activity Questionnaire Short Form (IPAQ-SF). PCOS-related quality of life questionnaire (PCOSQ) was also completed by the patients. RESULTS: While 48.5% of all participants gained weight, 13.9% maintained a stable weight, and 37.6% lost weight during the 14-week social isolation. The distribution of weight change was similar between groups (p = 0.44). All participants reported a decrease in physical activity (p < 0.001). While eating behavior showed no significant change in both groups, reduced sleep quality was found only in the PCOS group (p < 0.001). In women with weight gain, increase in BMI values was higher in patients (1.3 ± 1 kg/m2) than controls (1.0 ± 0.6 kg/m2; p = 0.01). Among those who gained weight, delta BMI values showed positive correlations with delta sleep induction time (r = 0.25, p = 0.001), delta PSQI (r = 0.24, p = 0.004) and delta TFEQ-18 scores (r = 0.25, p = 0.001). CONCLUSION: Weight changes during social isolation are similar in women with PCOS and healthy women. However, within those who gain weight, increase in BMI is more pronounced in women with PCOS. Weight gain appears to be related to alterations in sleep quality and eating habits rather than reduced physical activity. LEVEL III: Evidence obtained from cohort or case-control analytic studies.

Characterization of gut microbiota in polycystic ovary syndrome: Findings from a lean population.

BACKGROUND: Limited available animal and human data suggest an association between dysbiosis of gut microbiota and PCOS. We aimed to determine whether gut microbiota in lean women with PCOS shows any alterations compared to healthy women. MATERIALS AND METHODS: Twenty-four lean patients with PCOS phenotype A according to the Rotterdam 2003 diagnostic criteria and 22 BMI-matched healthy women were included in this study. Anthropometric, hormonal and biochemical measurements were carried out in all participants. 16S rRNA gene V3-V4 region amplicon sequencing was performed on stool samples. Preprocessing of the raw data was performed using QIIME, and both QIIME and R packages were used for microbiome analysis. RESULTS: Bacterial richness and diversity did not show a significant difference between patients and controls. Beta diversity was similar between the groups. However, Erysipelotrichaceae, Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, Planococcaceae, Gemmules and Bacillales were significantly abundant in PCOS group according to LEfSe analysis. Clostridium cluster XVII showed increased abundance in patient group, while Clostridium sensustricto and Roseburia were decreased compared to controls. Random forest prediction analysis revealed Clostridium cluster XIVb as the most discriminative feature of patient group and Roseburia for healthy controls. Testosterone and androstenedione were negatively correlated with alpha and phylogenetic diversity. CONCLUSIONS: Our results suggest that gut microbiome of lean PCOS patients with full phenotype shows compositional alterations with similar bacterial richness and diversity compared to controls and that hyperandrogenism is associated with dysbiosis.

Glucagon-like peptide-1, a matter of taste?

Understanding of gustatory coding helps to predict, and perhaps even modulate the ingestive decision circuitry, especially when eating behaviour becomes dysfunctional. Preclinical research demonstrated that glucagon like peptide 1 (GLP-1) is locally synthesized in taste bud cells in the tongue and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1 containing taste bud cells. In humans, the tongue has not yet been addressed as clinically relevant target for GLP-1 based therapies. The primary aim of the current review was to elaborate on the role of GLP- 1 in mammalian gustatory system, in particular in the perception of sweet. Secondly, we aimed to explore what modulates gustatory coding and whether the GLP-1 based therapies might be involved in regulation of taste perception. We performed a series of PubMed, Medline and Embase databases systemic searches. The Population-Intervention-Comparison-Outcome (PICO) framework was used to identify interventional studies. Based on the available data, GLP-1 is specifically involved in the perception of sweet. Aging, diabetes and obesity are characterized by diminished taste and sweet perception. Calorie restriction and bariatric surgery are associated with a diminished appreciation of sweet food. GLP-1 receptor agonists (RAs) modulate food preference, yet its modulatory potential in gustatory coding is currently unknown. Future studies should explore whether GLP-1 RAs modulate taste perception to the extent that changes of food preference and consumption ensue.

Influence of ethnicity on different aspects of polycystic ovary syndrome: a systematic review.

This systematic review aimed to assess variations in the clinical presentation and treatment outcomes of patients with polycystic ovary syndrome (PCOS) belonging to different ethnicities. A search was performed for studies comparing various clinical aspects of PCOS in two or more different ethnic groups. After screening 2264 studies, 35 articles were included in the final analysis. In comparison with White women with PCOS (wPCOS), East Asian women with PCOS (eaPCOS) were less hirsute, whereas Hispanic women with PCOS (hPCOS), South Asian women with PCOS (saPCOS) and Middle Eastern women with PCOS (mePCOS) were more hirsute. saPCOS had higher androgen and lower sex hormone-binding globulin (SHBG) concentrations, mePCOS had higher DHEAS concentrations, and hPCOS and Black women with PCOS (bPCOS) had lower SHBG and DHEAS measures than wPCOS. Menstrual disturbances were more frequent in eaPCOS. Both saPCOS and eaPCOS had lower body mass index with increased central adiposity. hPCOS and bPCOS were more obese. saPCOS, mePCOS, hPCOS and bPCOS had a higher prevalence of insulin resistance than wPCOS. bPCOS had a better lipid profile but higher blood pressure and cardiovascular risk. Indigenous Australian women with PCOS were more obese and more insulin resistant with higher androgen concentrations. The clinical phenotype of PCOS therefore shows a wide variation depending on ethnicity.

Tissue fat quantification by magnetic resonance imaging: proton density fat fraction in polycystic ovary syndrome.

RESEARCH QUESTION: What are the potential differences between lean women with and without polycystic ovary syndrome (PCOS) in fat content in liver, vertebrae, paraspinal muscles, pancreas, subcutaneous (SCAT) and visceral adipose tissue (VAT)? Magnetic resonance imaging proton density fat fraction (PDFF) was used to establish these differences. This is a novel, non-invasive, operator-independent method with comparable diagnostic sensitivity and specificity to histologic examination for fatty liver disease, and strong correlation with muscle strength in neuromuscular studies. DESIGN: Twenty lean women with PCOS (mean age 23.9 ± 2.3; body mass index [BMI] 22.4 ± 2.0) and 20 age- and BMI-matched healthy women (mean age 24.9 ± 1.5; BMI 21.5 ± 1.9) were enrolled in this cross-sectional study. Anthropometric, biochemical and hormonal evaluations along with magnetic resonance imaging proton density fat fraction were carried out. RESULTS: PDFF% measurements of liver, SCAT and VAT were higher in the PCOS group, indicating increased fat content in these areas in lean women with PCOS compared with controls (P = 0.045, 0.030 and 0.037, respectively). In contrast, PDFF% values of vertebrae and paraspinal muscles in the PCOS group were lower than controls (P = 0.038 and 0.05, respectively). Pancreatic PDFF% measurements were similar between the groups. In the PCOS group, PDFF% of VAT was positively correlated with free androgen index (r = 0.69, P = 0.002). CONCLUSIONS: PDFF% measurement, an MRI-based novel biomarker, reveals increased fat in liver, SCAT and VAT, and decreased fat in vertebral bones and paraspinal muscles of lean women with PCOS.

Circulating gut microbiota metabolite trimethylamine N-oxide and oral contraceptive use in polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is associated with an increased cardiometabolic risk that might not necessarily translate into adverse cardiovascular outcome later in life. Recently, alterations in gut microbial composition have been reported in the syndrome. Microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and its precursors are closely linked with development of atherosclerotic cardiovascular disease, independently of traditional risk factors. We aimed to assess whether TMAO and its precursors are altered in PCOS and to determine potential impact of treatment on these metabolites. DESIGN: Prospective study. PATIENTS: Twenty-seven overweight/obese patients with PCOS and 25 age- and BMI-matched healthy control women. MEASUREMENTS: At baseline, fasting serum TMAO and its precursors were measured after a 3-day standardized diet. Patients received 3-month OC therapy along with general dietary advice after which all measurements were repeated. RESULTS: Patients had higher total testosterone (T) and free androgen index (FAI) whereas whole-body fat mass, fasting plasma glucose, insulin and lipids were similar between the groups. PCOS group showed significantly higher serum levels of TMAO and its precursors; choline, betaine and carnitine. TMAO and choline showed correlations with T. After 3 months of OC use, TMAO and its precursors significantly decreased along with reductions in BMI, T and FAI. CONCLUSIONS: This study reports for the first time that TMAO and its precursors are elevated in PCOS which might contribute to increased cardiometabolic risk of the syndrome and that short-term OC use along with lifestyle intervention is associated with reduction of these microbiome-dependent metabolites.

Recommendations for epidemiologic and phenotypic research in polycystic ovary syndrome: an androgen excess and PCOS society resource.

STUDY QUESTION: What are the best practices for undertaking epidemiologic and phenotypic studies in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Best practices for the undertaking of epidemiologic and phenotypic studies in PCOS are outlined. WHAT IS KNOWN ALREADY: Currently methodologies used for studies of PCOS epidemiology and phenotypes vary widely, and the comparability of studies is low, reducing the ability to harmonize studies. STUDY DESIGN, SIZE, DURATION: The Androgen Excess and PCOS (AE-PCOS) Society established a Task Force to draft a research resource for epidemiologic and phenotypic studies in PCOS, with the aim of providing guidelines on study design and execution, insights into the limitations and alternatives and protocols to be used, taking into consideration a global perspective. PARTICIPANTS/MATERIALS, SETTING, METHODS: A targeted review of the literature was carried out as necessary. MAIN RESULTS AND THE ROLE OF CHANCE: High level recommendations include the following: (i) Before initiating the study, a number of critical factors should be addressed including selecting the population and diagnostic criteria (which should ideally align with the recommendations of the International Guidelines), the type of observational study to be undertaken and the primary and secondary endpoint(s) of the study.(ii) To assess the 'natural' or true phenotype and epidemiology of PCOS, the least medically biased, broadest and most generalizable population, and the broadest definition of PCOS, should be used.(iii) Four PCOS phenotypes (Phenotypes A through D), based on the presence or absence of three general features (oligo-anovulation, hyperandrogenism and polycystic ovarian morphology), should be ascertained.(iv) In epidemiologic and phenotypic studies, the detection of PCOS rests on the accuracy and sensitivity of the methods used for assessing the individual features of the disorder, and how 'normal' is defined.(v) Although an assessment algorithm that minimizes the use of certain measures (e.g. androgen levels and/or ovarian ultrasonography) can be devised, when possible it is preferable to uniformly assess all subjects for all parameters of interest.(vi) The inclusion of subjects in epidemiologic studies who do not appear to have PCOS (i.e. 'non-PCOS') will provide the necessary cohort to establish population-specific normative ranges for the various features of PCOS. (vii) Epidemiologic studies of PCOS in unselected populations will yield relatively limited numbers of PCOS subjects available for genetic study; alternatively, large population-based epidemiologic studies of PCOS will potentially generate large numbers of unaffected individuals that may serve as genetic controls. (viii) Epidemiologic studies of PCOS will benefit from a clear governance structure and should begin by informing, educating and engaging both the formal and informal leaders of the populations targeted for study. (ix) In designing their study investigators should, in advance, establish statistical power and recognize, manage and account for inherent biases. (x) Subjects suspected of having PCOS but who do not/cannot complete their evaluation (i.e. have 'possible PCOS') can be included by imputation, assigning them a 'diagnostic weight' based on those subjects of similar clinical phenotype that have completed the study. (xi) In obtaining, storing and retrieving subject data, subjects should be assessed consecutively using a uniform data collection form; providing as complete and in depth data as possible. (xii) Maintenance of both paper and electronic medical records should focus on ensuring data quality, accuracy and institutional ethical compliance, and familiarity with country-dependent laws, including biobanking-specific laws, tissue laws and research laws. (xiii) In obtaining and biobanking study samples, these should be ideally collected at the time of the first assessment. (xiv) Access to stored data sets should ideally be granted to other bona fide researchers conducting research in the public interest. (xv) SOPs detailing the exact method of each of the activities for handling the data and the samples are necessary to ensure that all methods are performed uniformly. (xvi) Epidemiologic studies of PCOS must be resourced adequately. LIMITATIONS, REASONS FOR CAUTION: As with all reports involving expert interpretation of experiential and published data, inherent individual biases are possible. This risk is minimized in the present study by including experts from varying fields of study, aligning with recent international evidence-based guidelines and obtaining consensus approval of the recommendations from the Task Force and the board of the AE-PCOS. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines should encourage investigators worldwide to undertake much needed epidemiologic studies of PCOS, increasing the validity, integrity and comparability of the data. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding. R.A. serves as consultant for Medtronic, Spruce Biosciences and Ansh Labs; has received research funding from Ferring Pharmaceuticals; and is on the advisory board of Martin Imaging; R.L. has received research funding from MSD Pharmaceuticals; J.L. has received fees and/or grant support from the Dutch Heart Association, The Netherlands Organisation for Health Research and Development (ZonMw), Ferring Pharmaceuticals, Danone, Euroscreen/Ogeda and Titus Health Care; H.T. receives grant funding from the National Health and Medical Research Council; K.K., L.M.-P., S.S.M. and B.O.Y. have no potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Anti-Müllerian hormone as a diagnostic tool for PCOS under different diagnostic criteria in an unselected population.

RESEARCH QUESTION: Is anti-Müllerian hormone (AMH) a valid tool to diagnose polycystic ovary syndrome (PCOS) according to different subsets of criteria among an unselected group of women? DESIGN: In this cross-sectional study, AMH concentrations were measured in an unselected group of women. The ability of AMH to diagnose PCOS according to National Institutes of Health (NIH), Rotterdam-2003 and Androgen Excess and PCOS Society (AE-PCOS) criteria was tested by using frozen serum aliquots (n = 392) that had been collected from a previous prevalence study of PCOS. RESULTS: The respective age and body mass index adjusted area under the curve (aAUC, 95% confidence interval) values were 0.80 (0.71-0.89), 0.74 (0.67-0.81) and 0.71 (0.64-0.79). When the definition of polycystic ovary morphology (PCOM) was set to an antral follicle count (AFC) of 20 instead of 12, the prevalence of syndrome dropped from 19.9% to 10.2% and from 15.3% to 8.9% according to Rotterdam-2003 and AE-PCOS criteria, respectively. In patients with Phenotype A, who had hyperandrogenism, ovulatory dysfunction and PCOM, AMH had an aAUC of 0.85 (0.77-0.92) to diagnose the syndrome. In Phenotypes B (hyperandrogenism + ovulatory dysfunction), C (hyperandrogenism + PCOM) or D (ovulatory dysfunction + PCOM), AMH had poor to fair ability to diagnose the syndrome. CONCLUSION: AMH has poor to fair validity to diagnose PCOS among an unselected group of women, except for patients bearing all features of the syndrome (Phenotype A). This finding is valid using the NIH, Rotterdam-2003 and AE-PCOS criteria and even after revising the definition of PCOM as AFC ≥20.

Is muscle mechanical function altered in polycystic ovary syndrome?

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women of reproductive age. The aim of the current study was to assess muscle mechanical function in PCOS and its relationship with hormonal and metabolic features of the syndrome. METHODS: The study included 44 women with PCOS, all having clinical or biochemical hyperandrogenism, chronic oligo-anovulation and PCOM, and 32 age- and BMI-matched healthy women. Anthropometric, hormonal and biochemical measurements were performed. Muscle mechanical function including lower limb explosive strength and average power (AvP) was measured using isokinetic dynamometry, a valid and reliable instrument for measuring muscle strength. RESULTS: The mean age and BMI of the women with PCOS and controls were 21.8 ± 3.2 versus 22.8 ± 3 years and 26.1 ± 5.4 versus 25.5 ± 5.7 kg/m2, respectively (p = NS for both). PCOS patients had higher androgen levels, whereas total and regional fat and lean body mass and insulin resistance parameters were similar between the groups. The peak muscle force output defined as the peak torque of knee extensor and flexor muscles was higher in normal weight women compared to overweight and obese (p < 0.05 for both) but did not differ in patients and controls. AvP determined by the time-averaged integrated area under the curve at 60°/s angular velocity was higher in the PCOS group for extension and flexion (50.3 ± 21.2 vs 42.1 ± 11.6 and 35.3 ± 27 vs 22.2 ± 11.1, respectively, p < 0.05 for both). These measurements were correlated with bioavailable testosterone (r = 0.29, p = 0.012, r = 0.36, p = 0.001, respectively). CONCLUSION: Muscle mechanical function is altered in PCOS. Women with PCOS have increased average lower limb power that is associated with hyperandrogenism.

Suppressed Adiponectin Levels and Increased Adiponectin Response to Oral Glucose Load in Lean Women with Severe Acne Normalizes after Isotretinoin Treatment.

BACKGROUND/AIM: Isotretinoin, the drug of choice for severe acne, might be associated with a decrease in insulin sensitivity. Adiponectin is an adipose tissue-derived protein that increases insulin sensitivity. In this study, we aimed to investigate adiponectin levels in postadolescent severe acne and the effect of isotretinoin on adiponectin levels. METHODS: Participants included 18 female patients with severe acne and 18 healthy women matched for age and body mass index (BMI). Acne patients completed a 6-month isotretinoin treatment. Anthropometric measurements, serum adiponectin, lipids, fasting glucose, fasting insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were determined, and a standard 2-h oral glucose tolerance test (OGTT) was performed in healthy women once and in patients with acne before and after treatment. RESULTS: At baseline, patients with acne had significantly lower serum adiponectin levels than controls. Isotretinoin treatment resulted in a significant increase in weight, BMI, and triglyceride and adiponectin levels. Glucose metabolism markers in patients with acne and controls were similar at baseline and did not change after treatment. Baseline OGTT in acne patients revealed an increased adiponectin response at 2 h, which was not present in healthy controls. Remarkably, this OGTT-induced adiponectin increment in acne patients was diminished after isotretinoin treatment. CONCLUSION: Adiponectin levels are differently regulated in women with severe acne and healthy controls in that circulating basal levels in patients are suppressed and show an increase in response to oral glucose load. Suppression of baseline adiponectin ameliorates after 6 months of isotretinoin treatment, reaching levels similar to those of healthy controls.

Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts.

PURPOSE: To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. METHODS: Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed. RESULTS: Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT. CONCLUSION: This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.

The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis.

STUDY QUESTION: What is the reported overall prevalence of polycystic ovary syndrome (PCOS) according to the criteria of the National Institutes of Health (NIH), Rotterdam or the Androgen Excess and PCOS Society (AE-PCOS Society)? SUMMARY ANSWER: The reported overall prevalence of PCOS (95% CI) according to diagnostic criteria of the NIH, Rotterdam and the AE-PCOS Society is 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. WHAT IS ALREADY KNOWN: PCOS is the most common endocrine disorder among women of reproductive age. Although many studies have investigated the prevalence of PCOS, there are discrepancies in their results, in part due to the use of various definitions of the syndrome and its subphenotypes, differences between study cohorts, ethnicities, and types of recruitment and sampling. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis were performed on all published studies that have reported the prevalence of PCOS according to at least one subset of diagnostic criteria. PARTICIPANTS/MATERIALS, SETTING, METHODS: To identify relevant studies based on the PRISMA statement, PubMed and Ovid databases were searched up to September 2015 by two blind investigators using the terms 'PCOS', 'polycystic ovarian disease', 'Stein Leventhal syndrome', 'Androgen Excess Society', 'National Institute of Health', 'Rotterdam', 'ESHRE/ASRM', 'criteria' and 'prevalence'. Articles that represented the prevalence of PCOS according to at least one subset of diagnostic criteria were included. Exclusion criteria were a focus on adolescent subjects, an absence of data on prevalence, inappropriate design or non-English reporting. An appraisal tool to evaluate the methodological quality of the available studies was generated by the authors. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 55 reports remained following screening of the abstracts and text for the subject of the study. Of these, 24 articles were eligible and evaluated for qualitative and quantitative synthesis. Since heterogeneity was observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The proportions of PCOS prevalence (95% CI) according to the diagnostic criteria of NIH, Rotterdam and AE-PCOS Society were 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. When only unselected population studies were included, the given rates were 6% (5-8%, n = 3 trials), 9% (7-12%, n = 6 trials) and 10% (7-14%, n = 3 trials). The respective proportions for hirsutism, hyperandrogenaemia, polycystic ovaries (PCO) and oligo-anovulation were 13% (8-20%, n = 14 trials), 11% (8-15%, n = 9 trials), 28% (22-35%, n = 12 trials) and 15% (12-18%, n = 19 trials), respectively. LIMITATIONS, REASONS FOR CAUTION: The effects of ethnic differences, particularly, on the presence or severity of hirsutism cannot be ruled out in any way. In addition, there was a lack of standardization in defining phenotypes of the syndrome and selection bias was evident in most of the studies regarding recruitment of the cohorts. WIDER IMPLICATIONS OF THE FINDINGS: Geographical differences in frequencies of the components of the syndrome, such as oligo-anovulation and clinical/biochemical androgen excess, must be taken into account in the development and implementation of regional diagnostic and precision treatment strategies. Further efforts and resources are required to increase standardization of the methods and comparability of the study results on prevalence and phenotypic characterization of PCOS around the globe. STUDY FUNDING/COMPETING INTERESTS: No funding to declare. The authors have no conflicts of interest to declare. REGISTRATION NUMBER: None.

Tumor deposits: Prognostic significance in gastric cancer patients.

PURPOSE: Tumor deposits (TDs) are defined as satellite peritumoral nodules in the peritumoral adipose tissue of a primary carcinoma without histologic evidence of residual lymph node in the nodule. We aimed to investigate the relation between TDs and clinicopathological characteristics of gastric cancer and to evaluate the effect of TDs on prognosis. METHODS: One hundred and seven non-metastatic gastric cancer patients were enrolled. The relationships between positive and negative TDs with respect to clinicopathological characteristics, as well as disease free survival (DFS) and overall survival (OS), were analyzed. RESULTS: TDs were detected in 28 patients (26.2%). Advanced pT stage and pN stage were significantly higher in TDs-positive compared to TDs-negative patients (p=0.015 and p=0.037, respectively). No significant differences were identified between the groups in other clinicopathological variables such as gender, lymphovascular and perineural invasion. Recurrence and mortality rates were higher in the TDs-positive patients during follow-up of both groups (22/78.6% vs 38/48.1%, p=0.010 for relapse; 20/71.4% vs 3/38%, p=0.005 for mortality). The univariate analysis demonstrated shorter DFS and OS for TDs-positive compared to TDs-negative patients. In multivariate analysis, TDs-positive patients had 1.75-fold higher likelihood to develop recurrence, while the likelihood of death increased 1.99-fold (p=0.041 and p=0.020, respectively). CONCLUSION: TDs-positive gastric cancers demonstrate a more aggressive clinical course compared to TDs-negative. More effective treatment methods should be necessary for management of this subgroup of gastric cancer.

[Turkish Hypertension Consensus Report]. / Türk Hipertansiyon Uzlasi Raporu.

Hypertension is a common and important public health problem in Turkey and worldwide. Recommendations on the diagnosis and treatment of hypertension have been presented in many nationally and internationally agreed European and American guidelines. However, there are differences among these guidelines, and some of the recommendations are not consistent with clinical practice in our country. Consensus report preparation, with the participation of relevant associations, was considered necessary to merge recommendations by evaluating hypertension guidelines from the perspective of Turkey and to create a joint approach in the diagnosis and treatment of hypertension in adults. For this purpose, it was aimed to prepare a practical text in Turkey in which all physicians dealing with hypertensive patients, from family practitioners in primary care to specialists in tertiary care, could come to agreement on common concepts, and which would be used as a basic reference guideline. Considering health care practices and sociocultural structure in Turkey, this report aimed to enhance awareness on hypertension, provide a common basis for different definitions and values as well as therapeutic options in various guidelines, and establish a practical reference guide to improve clinical practices in Turkey. This report is not a document describing hypertension in every aspect, but a reference, including basic recommendations with outlines. Care was taken to ensure that recommendations were evidence-based and valid for a majority of patients in clinical practice. However, it should be kept in mind that an approach assessment should be made on an individual basis for each patient.

Fasting and post-prandial glucagon like peptide 1 and oral contraception in polycystic ovary syndrome.

OBJECTIVE: We aimed to investigate whether fasting and meal regulated glucagon like peptide 1 (GLP-1) secretion are altered in patients with polycystic ovary syndrome (PCOS) compared to healty women and whether oral contraceptive use influence GLP-1 secretion dynamics in the syndrome. DESIGN: Prospective observational study. PATIENTS: Fourteen lean normal glucose tolerant patients with PCOS and 11 age- and body mass index (BMI)-matched healthy women. MEASUREMENTS: Glucagon like peptide 1, glucose and insulin levels were measured during a standardized meal tolerance test and area under the curves (AUCs) were calculated. Whereas healthy controls were assessed at baseline, all tests were repeated in women with PCOS after treatment with ethinyl estradiol 30 µg/drospirenone 3 mg (EE/DRSP) for 3 months. RESULTS: Both fasting and post-meal levels of GLP-1 were significantly reduced in women with PCOS compared to controls (P = 0·022 and P = 0·028, respectively). AUC for GLP-1 was also lower in PCOS (P = 0·012). Glucose and insulin measurements did not show a significant change between the groups. In the PCOS group, GLP-1, glucose and insulin levels did not show any change after 3 months of EE/DRSP use. CONCLUSION: GLP-1 levels both at fasting and in response to a meal are blunted in lean women with PCOS compared to healthy women. Short term oral contraception do not alter GLP-1 secretion in PCOS. Disturbance in incretin secretion dynamics might contribute to the risk of impaired glucose tolerance and type 2 diabetes in PCOS.