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Polycystic ovary syndrome (PCOS) is a prevalent condition that not only has the potential to impede conception but also represents the most common endocrine dysfunction in fertile women. It is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome’s risks. Undoubtedly, the impact of PCOS on infertility has attracted most of the attention of healthcare providers and investigators. However, there is growing evidence that even after conception is achieved, PCOS predisposes the parturient to several adverse pregnancy outcomes including a high risk of pregnancy-induced hypertension, spontaneous abortion, gestational diabetes, preeclampsia, and preterm birth, which increase the risks of stillbirth and neonatal death. Fetal growth abnormalities may also be more common, but the relationship is less well defined. This narrative review aims to summarize current knowledge regarding these conditions as they interplay with PCOS and concludes that although there appears to be an increase in these complications during the pregnancy of women with PCOS, there is a need for further research to clarify the possible confounding impact of obesity. Implications for clinical practice and future research are outlined.

Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the ‘Human Microbiome Project’ in 2016. We obtained 200 articles by inputting keywords such as ‘gut microbiome’, ‘gut microbiota’, ‘gut dysbiosis’, ‘PCOS’, and ‘endometrial cancer’ into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome.

Objective criteria have been scarce in published data on the occurrence of polycystic ovary syndrome (PCOS) in the United Arab Emirates (UAE). It is crucial that we enhance our comprehension of PCOS prevalence in the UAE to inform key stakeholders about the disease’s burden and enable comparisons with other nations. This research aimed to examine the PCOS prevalence at a large academic tertiary centre in Dubai, UAE, called Latifa Women and Children’s Hospital. We performed a cross-sectional study by reviewing the electronic medical records of patients accessing care between 2017 and 2022 (5 years). By utilizing the international classification of diseases codes (ICD-10), we discovered a period prevalence of PCOS of 1.6% among 64,722 women aged between 15 and 45 years. It is worth noting that the estimated annual point prevalence rose from 1.19% in 2020 (at the beginning of the COVID19 pandemic) to 2.72% in 2022 (after the start of the COVID-19 pandemic). Therefore, the odds ratio of the risk of a PCOS diagnosis in 2022 compared to 2020 was 2.28. The majority of the women diagnosed with PCOS in this study had an ICD-10 code of E28.2. Women with PCOS were younger than the controls, less likely to be pregnant, and had a higher body mass index and systolic and diastolic blood pressure. This is the most extensive research to date examining PCOS prevalence in the UAE, and it emphasizes the significance of this condition. It is crucial to prioritize PCOS to prevent morbidity and mortality from reproductive and long-term health consequences, including infertility, type 2 diabetes and endometrial cancer, which is presently the most frequent gynecological cancer in the UAE.

Endometrial cancer (EC) is the sixth most common cancer and the fourth leading cause of death among women worldwide. Early detection and treatment are associated with a favourable prognosis and reduction in mortality. Unlike other common cancers, however, screening strategies lack the required sensitivity, specificity and accuracy to be successfully implemented in clinical practice and current diagnostic approaches are invasive, costly and time consuming. Such limitations highlight the unmet need to develop diagnostic and screening alternatives for EC, which should be accurate, rapid, minimally invasive and cost-effective. Vibrational spectroscopic techniques, Mid-Infrared Absorption Spectroscopy and Raman, exploit the atomic vibrational absorption induced by interaction of light and a biological sample, to generate a unique spectral response: a “biochemical fingerprint”. These are non-destructive techniques and, combined with multivariate statistical analysis, have been shown over the last decade to provide discrimination between cancerous and healthy samples, demonstrating a promising role in both cancer screening and diagnosis. The aim of this review is to collate available evidence, in order to provide insight into the present status of the application of vibrational biospectroscopy in endometrial cancer diagnosis and screening, and to assess future prospects.

Background Clinical reasoning refers to the cognitive processes used by individuals as they formulate a diagnosis or treatment plan. Clinical reasoning is dependent on formal and experiential knowledge. Developing the ability to acquire and recall knowledge effectively for both analytical and non‐analytical cognitive processing has patient safety implications. This realist review examines the way educational interventions develop analytical and non‐analytical reasoning ability in undergraduate education. A realist review is theory‐driven, seeking not only to identify if an intervention works, but also understand the reasons why, for whom, and in what circumstances. Aim To develop understanding about the way educational interventions develop effective analytical and non‐analytical clinical reasoning ability, when they do, for whom and in what circumstances. Methods Literature from a scoping search, combined with expert opinion and researcher experience was synthesised to generate an initial programme theory (IPT). Four databases were searched and articles relevant to the developing theory were selected as appropriate. Factors affecting educational outcomes at the individual student, teacher and wider organisational levels were investigated in order to further refine the IPT. Results 28 papers contributed to the overall programme theory. The review predominantly identified evidence of mechanisms for interventions at the individual student level. Key student level factors influencing the effectiveness of interventions included an individual’s self‐confidence, self‐efficacy and pre‐existing level of knowledge. These contexts influenced a variety of educational interventions, impacting both positively and negatively on educational outcomes. Discussion Development of analytical and non‐analytical clinical reasoning ability requires activities that enhance knowledge acquisition and recall alongside the accumulation of clinical experience and opportunities to practise reasoning in real or simulated clinical environments. However, factors such as pre‐existing knowledge and self‐confidence influence their effectiveness, especially among individuals with ‘low knowledge’. Promoting non‐analytical reasoning once novices acquire more clinical knowledge is important for the development of clinical reasoning in undergraduate education.

Pre-eclampsia is the most common pregnancy complication affecting 1 in 20 pregnancies, characterized by high blood pressure and signs of organ damage, most often to the liver and kidneys. Metabolic network analysis of published lipidomic data points to a shortage of Coenzyme A (CoA). Gene expression profile data reveal alterations to many areas of metabolism and, crucially, to conflicting cellular regulatory mechanisms arising from the overproduction of signalling lipids driven by CoA limitation. Adverse feedback loops appear, forming sphingosine-1-phosphate (a cause of hypertension, hypoxia and inflammation), cytotoxic isoketovaleric acid (inducing acidosis and organ damage) and a thrombogenic lysophosphatidyl serine. These also induce mitochondrial and oxidative stress, leading to untimely apoptosis, which is possibly the cause of CoA restriction. This work provides a molecular basis for the signs of pre-eclampsia, why polycystic ovary syndrome is a risk factor and what might be done to treat and reduce the risk of disease.

Pre-eclampsia is the most common pregnancy complication affecting 1 in 20 pregnancies, characterized by high blood pressure and signs of organ damage, most often to the liver and kidneys. Metabolic network analysis of published lipidomic data points to a shortage of Coenzyme A (CoA). Gene-expression profile data reveal alterations to many areas of metabolism and, crucially, to conflicting cellular regulatory mechanisms arising from the overproduction of signalling lipids driven by CoA limitation. Adverse feedback loops appear, forming sphingosine-1-phosphate (a cause of hypertension, hypoxia and inflammation), cytotoxic isoketovaleric acid (inducing acidosis and organ damage) and a thrombogenic lysophosphatidyl serine. These also induce mitochondrial and oxidative stress, leading to untimely apoptosis, which is possibly the cause of CoA restriction. This work provides a molecular basis for the signs of pre-eclampsia, why other conditions are risk factors and what might be done to treat and reduce the risk of this and related diseases.

Background: To investigate any associations between new clinical policies implemented because of the COVID-19 pandemic and harm to patients. Methods: Retrospective data collection of incidents and complaints reported through Datix®, and the Patient Liaison Service respectively. The setting was the Family Health division in a University teaching hospital in the UK. Primary and secondary outcome measures included; Proportion of incidents reported on Datix from 23/3/20 to 25/5/20, compared to the period from 23/3/19 to 29/5/19. COVID-19 related incidents and complaints and association with newly published guidelines or pathways from 23/3/20 to 29/5/20. Results: There was no significant difference in the proportion of overall patient activity resulting in incidents reported on Datix in 2020 (2.08%) compared to 2019 (2.09%), with 98% resulting in no/low harm in 2020. Three incident categories had increases in relative proportions of incidents including terms “COVID” or “Corona” compared to incidents that did not; “Child death”, “delay/failure to treatment and procedure” and “information governance”. One of the child deaths was a miscarriage and we were unable to link the second child death to a change in clinical policy at this stage. We were only able to link 2 COVID-19 associated incidents with a pathway or procedural change (one to the Children's Emergency Department admission pathway and the second to the introduction of virtual antenatal clinics). Eighteen complaints related to COVID-19 were logged. However, at this stage, we are unable to link any of these to a published change in clinical policy. Conclusions: Practice in the division was overall deemed to be safe in the designated period, with only 2 COVID-19 related incidents clearly related to a change in pathways and procedures. Continued surveillance and improved metrics for monitoring the impact of changes to pathways and procedures should be sought with the sustained presence of COVID-19 in clinical areas.

Introduction Women with polycystic ovary syndrome have a three-fold higher risk of endometrial cancer. Insulin resistance and hyperlipidemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to investigate endometrial sterol regulatory element binding protein-1 gene expression in polycystic ovary syndrome and endometrial cancer endometrium, and to correlate endometrial sterol regulatory element binding protein-1 gene expression with serum lipid profiles. Material and methods A cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed. Results The body mass indices of women with polycystic ovary syndrome (29.28 ± 2.91 kg/m2) and controls (28.58 ± 2.62 kg/m2) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 ± 5.70 kg/m2). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p

This article was migrated. The article was marked as recommended. This opinion piece examines some of the literature on the impact of emotional wellbeing on cognitive load and the impact this might have on educational attainment. It discusses cognitive load theory and outlines a brief history of its evolution to our current understanding. The literature on the degree to which negative emotions contribute to cognitive load is explored, followed by the association between cognitive load and educational attainment in the context of cognitive load theory. The article concludes by making a case for increased awareness, highlighting the need for more empirical research and briefly examining the role of some potential interventions to optimise cognitive load in the context of emotional wellbeing and their potential impact on educational attainment.

Linton discusses a multi-pronged approach to tackling differential attainment.1 Another approach, not considered by Linton or the General Medical Council in its report published last year,2 is using the framework of cognitive load theory. Cognitive load theory proposes that, when learning, new information is stored in working memory, which is limited in …

The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). A total of 40 women, aged between 21 and 45 years with PCOS (Rotterdam criteria) were recruited. The participants were assessed at pre- and 3-month-post-Metformin therapy for the menstrual regularities, weight reduction, Ferriman Galway scores, fasting blood glucose (FBG), total cholesterol, LDL, HDL and p53, BCL-2 and cyclin D2 gene expression. Five participants conceived spontaneously after the initial recruitment. Majority (68%) resumed regular menstrual cycles after Metformin. There were significant reduction in BMI (p = 0.001), weight (p = 0.001) and Ferriman Galway scores (p = 0.001). A significant improvement was seen in mean FBG (p = 0.002), total cholesterol (p = 0.001), LDL (p = 0.003) and HDL cholesterol levels (p = 0.015). Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. BCL-2 and cyclin D2 (oncogenes) were slightly up-regulated without significant difference (p = 0.119 and 0.155, respectively). In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Further studies are however required to independently validate our findings.

BACKGROUND: Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. The levonorgestrel intrauterine device (Mirena Coil, Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA) may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown in some human studies to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. OBJECTIVES: To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Google Scholar, OpenGrey, Latin American Caribbean Health Sciences Literature (LILACS), and two trials registers from inception to 10 January 2017. We searched the bibliographies of all included studies and reviews on this topic. We also handsearched the conference abstracts of the European Society of Human Reproduction and Embryology (ESHRE) 2015 and the American Society for Reproductive Medicine (ASRM) 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross‐over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo or no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, extracted data from included studies, and assessed the risk of bias of included studies. We resolved disagreements by discussion or by deferment to a third review author. When study details were missing, review authors contacted study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. Secondary outcome measures included recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, hysterectomy rate, abnormal uterine bleeding, health‐related quality of life, and adverse effects during treatment. MAIN RESULTS: We included three RCTs in which a total of 77 women took part. We rated the quality of the evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision. We performed a meta‐analysis of two trials with 59 participants. When metformin was compared with megestrol acetate in women with endometrial hyperplasia, we found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (odds ratio (OR) 3.34, 95% confidence interval (CI) 0.97 to 11.57, two RCTs, n = 59, very low‐quality evidence), hysterectomy rates (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 59, very low‐quality evidence), and rates of abnormal uterine bleeding (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 44 , very low‐quality evidence). We found no data for recurrence of endometrial hyperplasia or health‐related quality of life. Both studies (n = 59) provided data on progression of endometrial hyperplasia to endometrial cancer as well as one (n = 16) reporting some adverse effects in the metformin arm, notably nausea, thrombosis, lactic acidosis, abnormal liver and renal function among others. Another trial including 16 participants compared metformin plus megestrol acetate versus megestrol acetate alone in women with endometrial hyperplasia. We found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (OR 9.00, 95% CI 0.94 to 86.52, one RCT, n = 16, very low‐quality evidence), recurrence of endometrial hyperplasia among women who achieve regression (OR not estimable, no events recorded, one RCT, n = 8, very low‐quality evidence), progression of endometrial hyperplasia to endometrial cancer (OR not estimable, no events recorded, one RCT, n = 13, very low‐quality evidence), or hysterectomy rates (OR 0.29, 95% CI 0.01 to 8.37, one RCT, n = 16, very low‐quality evidence). Investigators provided no data on abnormal uterine bleeding or health‐related quality of life. In terms of adverse effects, three of eight participants (37.5%) in the metformin plus megestrol acetate study arm reported nausea. AUTHORS' CONCLUSIONS: At present, evidence is insufficient to support or refute the use of metformin alone or in combination with standard therapy ‐ specifically, megestrol acetate ‐ versus megestrol acetate alone, for treatment of endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials yielding long‐term outcome data are needed to address this clinical question.

Background: UK biobank was set up to investigate the respective contributions of genetic predisposition and environmental exposure to the development of disease and recruited participants between 2006 and 2010. Our aim was to investigate the feasibility of using UK biobank for exploring the association between polycystic ovarian syndrome (PCOS) and endometrial cancer, including the role played by serum IGF-1 levels. Methods: Publicly accessible and freely available online data in the resource section of the UK biobank website were used to determine the prevalence of self reported PCOS and for assessing the quality of data on ovarian imaging and serum biomarkers. A literature review was conducted to compare rates of PCOS in UK Biobank with other populations. Results: UK biobank contains 273,469 women (age range 37-73 years) of whom 643 (0.23%) self-reported PCOS. This was compared with values ranging from 3.1 % to 19.9% obtained from 16 studies picked up by our systematic literature search. Conclusion: It is feasible to use UK biobank to conduct research into the role of IGF-1 in explaining the association between PCOS and endometrial cancer. More detailed phenotyping of women recruited into the diagnostic group of PCOS is, however, vital to underpin this research. The resulting resource would be excellent for researchers interested in exploring the long-term health risks associated with PCOS.

STUDY QUESTION Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). SUMMARY ANSWER Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls. WHAT IS KNOWN ALREADY Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known. STUDY DESIGN, SIZE, DURATION A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192. MAIN RESULTS AND THE ROLE OF CHANCE Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies. LIMITATIONS, REASONS FOR CAUTION The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues. WIDER IMPLICATIONS OF THE FINDINGS This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a well co-ordinated multidisciplinary collaboration of clinicians, basic scientists and mathematicians is vital. STUDY FUNDING/COMPETING INTEREST(S) No financial support was obtained for this project. There are no conflicts of interest.

The aim of this study was to independently validate proteomic biomarkers previously reported to be differentially expressed in women with Polycystic Ovary Syndrome (PCOS) compared with controls. This study focused on plasma proteomic biomarkers.This was a cross-sectional study at the University of Nottingham, in which samples from 30 PCOS and 30 control women were analysed by Western blotting.Mean abundance ratios from Western blots of plasma total haptoglobin and haptoglobin beta proteins were 1.25 (CI 1.11-1.4) and 1.24 (CI 1.04-1.44). The mean abundance ratio from the blots of alpha-2 macroglobulin was however 1.05 (CI, 1-1.1). The mean PCOS/control BMI ratio was 1.18 (CI 1.17-1.20). There was no correlation between PCOS/control BMI ratio and alpha-2 macroglobulin, total haptoglobin and haptoglobin beta abundance ratios. There was also no correlation between PCOS/control insulin ratio and alpha-2 macroglobulin, total haptoglobin and haptoglobin beta abundance ratios.Total haptoglobin and haptoglobin beta chain protein abundance was found to be elevated in women with PCOS compared with controls. We were unable to confirm decreased alpha-2 macroglobulin levels as reported in a previous study. Independent validation studies are required to validate early promising proteomic biomarkers in PCOS.

There is a need for research studies into the molecular mechanisms underpinning the link between polycystic ovary syndrome (PCOS) and endometrial cancer (EC) to facilitate screening and to encourage the development of novel strategies to prevent disease progression. The objective of this review was to identify proteomic biomarkers of EC risk in women with PCOS. All eligible published studies on proteomic biomarkers for EC identified through the literature were evaluated. Proteomic biomarkers for EC were then integrated with an updated previously published database of all proteomic biomarkers identified so far in PCOS women. Nine protein biomarkers were similarly either under or over expressed in women with EC and PCOS in various tissues. These include transgelin, pyruvate kinase M1/M2, gelsolin-like capping protein (macrophage capping protein), glutathione S-transferase P, leucine aminopeptidase (cytosol aminopeptidase), peptidyl-prolyl cis-transisomerase, cyclophilin A, complement component C4A and manganese-superoxide dismutase. If validated, these biomarkers may provide a useful framework on which the knowledge base in this area could be developed and will facilitate future mathematical modelling to enhance screening and prevention of EC in women with PCOS who have been shown to be at increased risk.

Women with polycystic ovary syndrome (PCOS) are at increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In this study, we attempted to list the proteomic biomarkers of PCOS and T2DM that have been published in the literature so far. We identified eight common biomarkers that were differentially expressed in both women with PCOS and T2DM when compared with healthy controls. These include pyruvate kinase M1/M2, apolipoprotein A-I, albumin, peroxiredoxin 2, annexin A2, α-1-B-glycoprotein, flotillin-1 and haptoglobin. These biomarkers could help improve our understanding of the links between PCOS and T2DM and could be potentially used to identify subgroups of women with PCOS at increased risk of T2DM. More studies are required to further evaluate the role these biomarkers play in women with PCOS and T2DM.

Introduction Endometrial hyperplasia is a precancerous lesion of the endometrium, commonly presenting with uterine bleeding. If managed expectantly, it frequently progresses to endometrial carcinoma, rates of which are increasing dramatically worldwide. However, the established treatment for endometrial hyperplasia (progestogens) involves multiple side effects and leaves the risk of recurrence. Metformin is the most commonly used oral hypoglycaemic agent in type 2 diabetes mellitus. It has also been linked to the reversal of endometrial hyperplasia and may therefore contribute to decreasing the prevalence of endometrial carcinoma without the fertility and side effect consequences of current therapies. However, the efficacy and safety of metformin being used for this therapeutic target is unclear and, therefore, this systematic review will aim to determine this. Methods and analysis We will search the following trials and databases with no language restrictions: Cochrane Gynaecology and Fertility Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; EBSCO Cumulative Index to Nursing and Allied Health Literature; PubMed; Google Scholar; ClinicalTrials.gov; the WHO International Trials Registry Platform portal; OpenGrey and the Latin American and Caribbean Health Sciences Literature (LILACS). We will include randomised controlled trials (RCTs) of use of metformin compared with a placebo or no treatment, conventional medical treatment (eg, progestogens) or any other active intervention. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. Trial authors will be contacted for additional data. The primary review outcome is the regression of endometrial hyperplasia histology towards normal histology. Secondary outcomes include hysterectomy rate; abnormal uterine bleeding; quality of life scores and adverse reactions to treatments. Ethics and dissemination Dissemination of the completed review will be through the Cochrane Library as well as through presenting the results at appropriate conferences.

The aim of this study was to investigate whether women with polycystic ovary syndrome (PCOS) had a unique metabolomic profile that was different from controls and to assess the feasibility of a definitive study. Twelve women with PCOS and 10 healthy women as controls had measurements of demographic and anthropometric data, venepunctures and assays on plasma samples for metabolomic profiles using hydrogen-1, nuclear magnetic resonance ((1)H NMR) spectroscopy. There did not appear to be any clear differences between the metabolomic profiles of women with PCOS compared with controls when the NMR spectra were visually inspected and initial principal component analysis showed only a subtle differentiation between the two groups which was spread over three principal components. However, 'supervised' data analysis in the form of partial least-squares discriminant analysis (PLS-DA) and non-parametric univariate analysis allowed a stable PLS-DA model to be built, which appeared to differentiate between the two groups in a robust manner. Peak assignments for those spectral regions which appeared to differentiate between control and PCOS were consistent with amino acids (arginine, lysine, proline, glutamate and histidine), organic acids (citrate) and potentially lipids (CH(2)-CH(2)-C=C) with significant decreases noted in the levels of citrulline, lipid (CH(2)-CH(2)-C=C), arginine, lysine, ornithine, proline, glutamate, acetone, citrate and histidine in PCOS compared with controls. Women with PCOS may have a unique metabolomic finger print and a definitive study is feasible. These findings may enable sample size calculations for confirmatory studies and stimulate further research using metabolomics to improve the understanding and management of PCOS.

Given the current lack of clarity in the published literature, we performed a systematic review of the literature to determine the exact strength of the association between polycystic ovary syndrome (PCOS) and endometrial cancer (EC).All published studies on the association between PCOS and EC identified through MEDLINE (1966-April 2011), EMBASE (1980-April 2011) and Cochrane (1998-April 2011). Original data were abstracted where available and summarized on a separate Microsoft Excel (2007) database for analysis. A total of 14 studies comparative and non-comparative were identified and included.The non-comparative and comparative data suggested that women with PCOS were more likely to develop EC. A meta-analyses of five comparative studies showed an increased risk of EC in women with an odds ratio of 2.89 with a 95% confidence interval of 1.52-5.48.Women with PCOS are about three times more likely to develop EC compared with women without it. This translates into a 9% lifetime risk of EC in Caucasian women with PCOS compared with 3% in women without it. Although most women (91%) with PCOS will not develop endometrial cancer, our study has shown that they are more likely at increased risk. More studies are required to clarify the exact molecular mechanisms, determine the best way of screening and preventing disease progression.

There is a need to identify biomarkers of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) risk in women with PCOS to facilitate screening and the development of novel strategies to prevent disease progression. Metabolomic technologies may address this need. All published studies on metabolomic biomarkers of IGT and/or T2DM identified through MEDLINE (1966-December 2010), EMBASE (1980-December 2010) and Cochrane (1993-December 2010) were retrieved. Eligible studies were screened and specific study characteristics recorded including study design, number of participants, selection criteria, type of metabolomic technique used, site of sample collection, and a list of metabolites identified to have been altered in IGT and/or T2DM versus healthy controls was created. Nine metabolomic biomarkers that could potentially be used to identify women with PCOS at risk of developing IGT and/or T2DM were identified including leucine, isoleucine, citrate, glucose, creatinine, valine, glutamine, alanine and HDL. Of these biomarkers, a panel of four biomarkers were consistently either elevated or reduced including glucose (elevated), valine (reduced), HDL (reduced) and alanine (reduced) in IGT/T2DM compared with controls. These biomarkers may predict the development of IGT/T2DM in young women with PCOS. More studies are required to test this hypothesis and translate the findings into patient benefit by reducing the morbidity/mortality associated with IGT/T2DM in PCOS.

The study objective was to investigate whether ultrasound (US) monitoring is essential during treatment with clomiphene citrate (CC) for ovulation induction, as recommended by the Royal College of Obstetricians and Gynaecologists (RCOG) and the National Institute for Clinical Excellence (NICE). We performed a systematic review of all studies investigating the effects of US in the treatment of ovulatory dysfunction with CC. The main objective of this review was to investigate whether US monitoring during CC treatment reduced multiple pregnancy rates. There was insufficient evidence to suggest that US monitoring reduces multiple pregnancy rates or improves pregnancy rates. On the other hand, no indication that treatment with CC is safe without US monitoring was identified. The small number of relevant studies and the heterogeneity observed in the methodologies of each study prohibit reliable conclusions to be drawn. There is currently no basis for amending the evidence base (good-practice points) used in the RCOG and NICE guidelines, which recommend the use of US to monitor the ovaries during stimulation with CC.

The aim of this study was to evaluate the number of surgeons required to successfully complete a range of gynaecological laparoscopic procedures using a new device (the Atiomo-Laparoscopic Assistant™), which enables one surgeon to easily simultaneously manipulate the uterus and the laparoscope. The number of surgeons required to complete the operation in 15 women undergoing a range of laparoscopic procedures using the Atiomo-Laparoscopic Assistant™ was compared with data retrospectively collected from theatre records. It was possible for one surgeon to assess the pelvis during laparoscopy in 10 (67%) of the 15 procedures where the Atiomo-Laparoscopic Assistant™ was used, compared with 177 of the 599 (30%) procedures where it was not used (p = 0.005). However, with the Mark 3 device, it was possible for one surgeon to perform the procedure in all seven procedures (100%) where it was used. Surgeons felt that the device was easy to use and no complications occurred.

Objective To identify the most commonly used methods for weight reduction in women with polycystic ovarian syndrome (PCOS) utilized by obstetricians and gynaecologists in the United Kingdom (UK). Study design Permission was sought from the Royal College of Obstetricians and Gynaecologists (RCOG) to conduct an electronic survey of all consultants practising in the UK. The questionnaire was anonymous and an electronic link was sent via email to the 1140 consultants whose details were provided by the RCOG. A 27-item questionnaire was developed. The variables evaluated were first-line methods of weight reduction used, proportion of women with PCOS seen that were obese, whether the patients had tried other weight reduction methods before seeking help, the optimal dietary advice and optimal composition, the optimal duration and frequency of exercise suggested, BMI used for suggesting weight loss, percentage of women in whom weight loss worked, length of time allowed prior to suggesting another method, methods considered most effective by patients, use of metformin for weight loss, criteria used for prescribing metformin, first-line anti-obesity drugs preferred if any, second- and third-line methods used, referral to other specialists and criteria for referral for bariatric surgery. Responses were categorical and are reported as proportions. Results One hundred and seven (9.4%) consultants responded to the questionnaire. One hundred and four (97%) provided advice on diet and 101 (94%) advice on exercise as their first-line strategy for weight management. Fifty-one (47.7%) stated that they provided specific information on an optimal dietary intake, 53 (49.9%) on the optimal dietary composition and 61 (57%) on the optimal duration and frequency of exercise per week. The commonest second-line methods used were anti-obesity drugs and metformin and the most popular third-line management options were anti-obesity drugs and bariatric surgery. Conclusions The results suggest that the information provided to women with PCOS on weight management is variable, and highlight the need for specific guidelines and further research on weight management in women with this condition.

Objective Feasibility of a clinical-trial comparing a low-glycaemic diet with a low-calorie healthy eating approach at achieving weight loss and reducing the risk of endometrial cancer in women with PCOS. Design A pilot Randomised-Controlled-Trial using different recruitment strategies. Setting A University Hospital in the United Kingdom. Patients Women seen at specialist gynaecology clinics over a 12 month period in one University Hospital, and women self identified through a website and posters. Interventions Potential recruits were assessed for eligibility, gave informed consent, randomised, treated and assessed as in the definitive trial. Main outcome measures Eligibility and recruitment rates, compliance with the allocated diet for 6 months and with clinical assessments, blood tests, pelvic ultrasound scans and endometrial biopsies. Results 1433 new and 2598 follow up patients were seen in 153 gynaecology clinics for over 12 months. 441 (11%) potentially eligible women were identified, 19 (0.4%) of whom met the trial entry criteria. Eleven consented to take part, of which 8 (73%) completed the study. Conclusions Planned future trials on over-weight women with PCOS should be multicentre and should incorporate primary care. This data will help other researchers plan and calculate the sample size and potential recruitment rates in future clinical trials in PCOS. The results will also be useful for inclusion in future meta-analyses.

Constructivist theories of learning describe learning as an active process in which learners construct new ideas or concepts based upon their past knowledge or experiences. This makes problem-based learning very attractive compared with traditional medium / large group lectures, which are thought to encourage passive assimilation of knowledge. Prob- lem based learning can however be labor intensive for faculty particularly with medium / large student bodies. This article explores the practicality of a pedagogic application of the constructivist theory of learning, which can be applied to a me- dium / large body of students in a traditional lecture called the contextual learning model. Students found the sessions en- joyable and interactive and thought the sessions stimulated their thinking, introduced new material and facilitated the far transfer of knowledge.

Objective To survey the preferences and variations in the current use of first- and second-generation endometrial ablative techniques for menorrhagia among the consultant gynecologists in the United Kingdom, given the call for further studies to systematically compare the clinical effectiveness of the various endometrial ablation techniques. Design Postal questionnaire survey. Population One thousand, four hundred sixty consultant gynecologists in the United Kingdom. Main Outcome Measure(s) Preferred endometrial ablation/resection method and variations in the current practices. Result(s) Six hundred ten (41%) consultants responded. Of these, 449 (73%) performed endometrial ablation/resection. Thermal balloon ablation (32.1%) was the preferred method, followed by microwave endometrial ablation (29.8%), transcervical resection of the endometrial alone or combined with roller ball diathermy (18.5%), Novasure (9.8%), hydrotherm ablation (6.9%), roller ball (2%), and laser (0.9%). Patient response to treatment was assessed using clinical history (64.3%), menstrual calendar (7.6%), clinical history and menstrual calendar (21.3%), questionnaires (5.8%), and pictorial blood loss assessment charts (0.4%). A total of 52.2% used gonadotrophin releasing hormone analogues preoperatively. Variations in techniques for transcervical resection of the endometrial included methods used to treat the uterine fundus and cornuae, fluid management, and operating pressures. Conclusion(s) Second-generation endometrial ablation devices were preferred to first-generation devices for the management of menorrhagia. Thermal balloon ablation was the most preferred method. However, variations in surgical practices will make assessment of clinical efficacy a challenge.

A variety of prefractionation methods (including a novel reversed-phase solid-phase-extraction (RP-SPE) combined with SDS-PAGE and proteomic based approaches (e.g., 2-dimensional gel electrophoresis (2DE) and MALDI-TOF mass spectrometry combined with Artificial Neural Network (ANN) bioinformatic tools) were used to investigate the protein/peptide signatures in patients with Polycystic Ovary Syndrome (PCOS). Four potential PCOS biomarkers were identified (complement C4alpha3c and C4gamma and haptoglobin alpha and beta chains).

The aim of this study was to determine whether first-degree male relatives of women with polycystic ovary syndrome (PCOS) were at increased risk of cardiovascular disease (CVD) and diabetes mellitus (type II DM). In a cross-sectional study, 60 women with PCOS and 112 controls were given a questionnaire. The prevalence of heart disease, stroke, diabetes and associated risk factors among fathers and brothers of women with PCOS and controls, were measured. The percentage of women with PCOS with at least one brother with a risk factor for CVD was 47.5%, around twice that seen in control women (24.71%). The prevalence of heart disease, stroke and diabetes were similar in brothers of women with PCOS and controls. In conclusion, brothers of women with PCOS may be at increased risk of CVD. They form an easily identified group, which can be targeted for primary prevention.

BACKGROUND\ud \ud Endometrial cancer (EC) is the most common gynaecological cancer amongst women in the UK. Although previous studies have found that women with polycystic ovary syndrome (PCOS) have at least a three-fold increase in endometrial cancer (EC) risk compared to women without PCOS, the precise molecular mechanisms which link between PCOS and EC remain unclear. It has been suggested that insulin resistance may contribute to the increased risk of EC in PCOS. The specific expression of genes related to the insulin-signalling pathway including the IGF system in the endometrium of women with PCOS has however never been measured and compared to that in women with EC without PCOS and control women without EC or PCOS. .\ud \ud OBJECTIVES\ud \ud To test the hypothesis that insulin signaling plays a key role in the development of EC in women with PCOS by measuring and comparing the expression of three key genes involved in the insulin signaling pathway (IGF1, PTEN and IGFBP1) in endometrial tissue obtained from three groups of women; PCOS without EC, women with EC without PCOS and non-PCOS women without EC (controls). We also aimed to determine the correlation between the gene expressions to various clinical variables among participants.\ud \ud METHODS\ud \ud This was a cross-sectional study of 102 women in 3 groups (PCOS, EC and controls) at a University teaching hospital in the United Kingdom. Clinical assessment (blood pressure, body mass index (BMI) and waist-hip-circumference ratio), venepuntures (fasting blood sugar, insulin, lipid profile, hormones) and endometrial tissue biopsies were taken in all participants. Endometrial tissue RNA extraction was performed before real time polymerase-chain-reaction for the genes of interest (IGF1, IGFBP1 and PTEN) was carried out. To compare the baseline characteristics of the study population, One-Way-ANOVA test or the Independent t-test was used. For variables that were not normally distributed, the Spearman correlation test was used to calculate the r value. A "p" value of

Genomic studies in polycystic ovary syndrome (PCOS) have focused on ovarian tissues and gene expression changes related to the gynaecological manifestations of PCOS. These studies have revealed a variety of altered genes that fall into many functional categories. Of these, the genes involved in steroidogenesis, including genes related to retinoic acid biosynthesis and LH-stimulated gene pathways, are generally up-regulated in PCOS samples. Genes involved in the Wnt signalling pathway appear down-regulated. Immune response genes and those involved in apoptosis are altered, but the net effect of these alterations is unclear at present. However, these altered gene expression patterns are yet to produce a defined aetiological basis or diagnostic biomarker for PCOS. The use of proteomic technologies for the study of the PCOS proteome is in its infancy; however, a few pilot studies have been published and the data are reviewed. Proteomics looks directly at the functional units within a cell, the proteins. This approach should thus serve to validate some of the gene expression changes identified and then build on the genomic results collected to date.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk of endometrial cancer (EC), albeit of a more differentiated type with better prognosis than in normal women. This study was designed to test these assumptions, as evidence for them is lacking. METHODS: The prevalence of polycystic ovaries (PCO), as a marker of PCOS, was investigated in ovarian sections from 128 women with EC and 83 with benign gynaecological conditions. The expression of the prognostic markers p53, Ki67, Bcl2 and cyclin D1 was also investigated by immunohistochemistry in endometrial tumours from 11 women with PCO and 16 with normal ovaries. RESULTS: Overall, PCO were similarly prevalent in women with EC (8.6%) and benign controls (8.4%); however, in women aged < 50 years, PCO were more prevalent in women with EC (62.5 versus 27.3%, P = 0.033). Cyclin D1-expressing endometrial tumours tended to be more prevalent in women with PCO compared to normal ovaries (36.4 versus 6.25%, respectively, P = 0.071). Bcl2-, p53- and Ki67-expressing tumours were similarly prevalent. CONCLUSIONS: The association between PCOS and EC appears confined to premenopausal women. The tendency for cyclin D1-expressing endometrial tumours to be more prevalent in women with PCO challenges the assumption that EC prognosis is improved in women with PCOS.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility and is conventionally treated with clomifene. Recent research shows that insulin resistance and hyperinsulinaemia lead to hyperandrogenism in PCOS. It is thought that this causes anovulation and infertility and is the rationale for the use of insulin-sensitising drugs such as metformin. This article explores the role of metformin, which is being increasingly used as first-line therapy to treat infertility with PCOS and potentially avoids the risks of multiple pregnancy and ovarian hyperstimulation associated with clomifene.

Polycystic ovary syndrome is one of the most common endocrine disorders in the human, affecting approximately 10% of women of reproductive age. Although originally considered a gynaecological disorder, the syndrome is associated with a wide range of endocrine and metabolic abnormalities, including insulin resistance. Affected women are at an increased risk of developing gestational and non-insulin dependent diabetes and there is an association with cardiovascular risk factors including obesity, hypertension, dyslipidaemia, hyperhomocysteinaemia, increased intima media thickness and impaired vascular elasticity. The effect on cardiovascular mortality is currently unclear. However, in view of the proven links with diabetes and the cardiovascular risk markers, this condition should be considered within the province of physicians as well as gynaecologists.

In 1935, a specific ovarian morphology of cystic and enlarged ovaries was described at laparotomy in seven women with obesity, amenorrhea or menstrual irregularity, hirsutism, and infertility. In several further studies in the 1950s and ‘70s, specific endocrine features of increased luteinizing hormone levels and hyperandrogenemia were described in these women. In the early ‘70s, with the availability of ultrasonography (US), noninvasive assessment of the ovaries was possible and, in 1985, a characteristic US appearance of polycystic ovaries was described. However, debate has remained concerning the correlation between the finding of polycystic ovaries on US and the clinical phenotype—some studies have shown that as many as 33% of apparently normal women will have polycystic ovaries. The etiology of polycystic ovary syndrome (PCOS) is also unknown. In 1935, Stein and Leventhal suggested a primary ovarian defect; however, more recently, a lot of interest has been focused on the role of insulin resistance as a common unifying hypothesis for the varied manifestation of this syndrome. Insulin resistance also has wider health implications such as diabetes, hypertension, and cardiovascular disease, and researchers are trying to quantify the risks of these conditions in PCOS. Therapy has evolved from a philosophy of primarily targeting the presenting clinical problem to ameliorating insulin resistance, which is now thought to be the primary defect. Improving insulin resistance has been shown to improve periods, fertility, and hyperandrogenemia. However, there remains some controversy as to the exact origin of this syndrome and it is still unknown which came first, “the insulin or the egg.”

Summary Objective Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). Aim To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. Design and Methods Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross‐sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study. Results We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P

Not all women with the polycystic ovary syndrome (PCOS) on ultrasound (US) will have the syndrome, and clinical and biochemical features of PCOS may be present without US features. The sensitivity of US in detecting PCOS was, therefore, prospectively determined in 72 women (32 PCOS and 40 controls). The most sensitive features were the presence of 10 or more follicles (82% and 69% in the left and right ovary) and a peripheral distribution of follicles (81.8% and 71.9% in the left and right ovary). Although ovarian enlargement and stromal brightness were not as sensitive as the previous criteria, stromal brightness was most specific. Combining all the criteria predicted a diagnosis of PCOS or control correctly in 86.4% of cases. This study shows that established US criteria of polycystic ovaries remain of value in the diagnosis of PCOS; however, the discrepancy between the left and right ovaries is an interesting but unexplained finding.

Summary BACKGROUND It has been postulated that an insulln-driven increase in plasminogen activator inhibitor-1 (PAI-1) levels may link insulin resistance to anovulatory infertility in women with PCOS and that It may place them at increased risk of thromboembolic disease. However, previous studies have been conflicting because many have failed to control for body mass index (BMI) which may affect PAI-1. The aim of this study was to investigate PAI-1 activity in women with PCOS and to compare it with unaffected controls of a similar BMI. DESIGN AND PATIENTS 41 Women with Pcos and 25 weight-matched controls participated in this cross-sectional study. Patients were evaluated clinically and by pelvic ultrasound and fasting blood samples were taken for haematological and biochemical tests. MEASUREMENTS PAI-1 activity, insulin, glucose, trlglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, FSH, LH, PRL, testosterone, SHBG, 17–hydroxyprogesterone, plasminogen, fibrinogen (α2 antiplasmin, blood pressure and insulin sensitivity with a homeostasis model assessment (HOMA) computer programme. RESULTS There was no significant difference in BMI or in (log) PAI-1 activity in women with PCOS compared with controls (BMI 29.5 ± 5.6 vs. 28.4 ± 6.3 kg/m2, P=0.25 and PAI-12.56 (SD 0.85) vs. 2.14 (SD 0.98) au/ml, P=0.07). The median fasting insulin level was significantly higher (17 (4.6–134.5) vs. 9.6 (3.7–41.5) mU/l, P

Current data indicate that there is a significant risk of endometrial cancer (EC) in women with polycystic ovarian syndrome (PCOS), although further research needed to clarify the exact molecular mechanisms. Endometrial hyperplasia is a premalignant condition that usually heralds EC and it shares identical risk factors with EC. Metabolic syndrome with a triad of obesity, hyperinsulinaemia and diabetes, which is commonly observed in PCOS appears to be a key mechanism in EC pathogenesis. Measures to improve insulin resistance could therefore play a role in reducing the risk of EC in women with PCOS. Metformin is an insulin sensitising agent which is safe, widely available and currently licensed for type-2 diabetes. It has been clearly shown in both animal and human studies that metformin is of value in reversing endometrial hyperplasia. Metformin may therefore prevent EC in PCOS. This article reviews the use of metformin in reducing EC risk in PCOS and makes a case for future research on this topic.

The aim of this study was to systematically review the evidence for the impact of scrotal cooling on spermatogenesis. EMBASE (1980-2010) and MEDLINE (1950-Sept. 2010) databases were searched using the terms 'male infertility or subfertility or fertility', combined with a separate search of 'scrotal cooling', without any limits or restrictions. A total of eight articles met the criteria for inclusion in the study. There was insufficient evidence to draw any firm conclusions about the impact of scrotal cooling on male fertility. A positive trend of improved male fertility was however observed. There is therefore a need for well designed randomised controlled trials.

Endometrial cancer (EC) is the commonest gynaecological cancer in North American and European women. Even though it has been shown that women with polycystic ovary syndrome (PCOS) have a three-fold increase in the risk of developing EC compared to women without PCOS, the precise molecular mechanisms which increase EC risk in women with PCOS remain unclear. Clinical strategies to prevent EC in PCOS are therefore not well researched and understood. Although raised estrogen levels, hyperinsulinaemia and, reduced apoptosis have been suggested as potential mechanisms, there is a lack of clarity about how these factors and other factors may interact to increase EC risk in PCOS. This article reviews the literature, on the potential molecular links between PCOS and EC but argues for a paradigm shift, to a systems biology-based approach in future research into the molecular links between PCOS and EC. The potential challenges of a systems biology-based approach are outlined but not considered insurmountable.

Objective To confirm whether there was a familial association between polycystic ovary syndrome (PCOS) and thromboembolic disease, ovarian or breast cancer, diabetes, and heart disease. Design Cross-sectional study. Setting A university hospital in the United Kingdom. Patient(s) Two hundred and seventeen women with and without PCOS under the care of the same consultant gynecologist at a teaching hospital. Intervention(s) Questionnaire survey. Main outcome measure(s) Prevalence of a personal or positive family history of thromboembolism, ovarian cancer, breast cancer, diabetes, and heart attacks. Result(s) In an analysis of the replies from 41 women with PCOS and 66 controls, we found a statistically significant positive family history of breast cancer and heart attacks among women with PCOS. There was no statistically significant difference in the mean age, ethnic origin, or prevalence of a family history of other diseases. Conclusion(s) Our results show a positive association between polycystic ovary syndrome and a family history of breast cancer and heart disease. These associations may be genetic in origin, or secondary to a complex interplay of genetic, intrauterine, and environmental factors. More studies are required to confirm these findings and determine the factors that explain these associations.

Women with polycystic ovary syndrome (PCOS) are at increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In this study, we attempted to list the proteomic biomarkers of PCOS and T2DM that have been published in the literature so far. We identified eight common biomarkers that were differentially expressed in both women with PCOS and T2DM when compared with healthy controls. These include pyruvate kinase M1/M2, apolipoprotein A-I, albumin, peroxiredoxin 2, annexin A2, α-1-B-glycoprotein, flotillin-1 and haptoglobin. These biomarkers could help improve our understanding of the links between PCOS and T2DM and could be potentially used to identify subgroups of women with PCOS at increased risk of T2DM. More studies are required to further evaluate the role these biomarkers play in women with PCOS and T2DM.

Objective To review and identify possible biomarkers for ovarian cancer (OC) in women with polycystic ovary syndrome (PCOS). Design Systematic literature searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics," "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers for OC were then integrated with an updated previously published database of all proteomic biomarkers identified to date in patients with PCOS. Setting Academic department of obstetrics and gynecology in the United Kingdom. Patient(s) A total of 180 women identified in the six studies. Intervention(s) Tissue samples from women with OC vs. tissue samples from women without OC. Main Outcome Measure(s) Proteomic biomarkers, proteomic technique used, and methodologic quality score. Result(s) A panel of six biomarkers was overexpressed both in women with OC and in women with PCOS. These biomarkers include calreticulin, fibrinogen-γ, superoxide dismutase, vimentin, malate dehydrogenase, and lamin B2. Conclusion(s) These biomarkers could help improve our understanding of the links between PCOS and OC and could potentially be used to identify subgroups of women with PCOS at increased risk of OC. More studies are required to further evaluate the role these biomarkers play in women with PCOS and OC.