Metformin for endometrial hyperplasia.

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 that are currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. A levonorgestrel intrauterine device 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. This is an update of a review first published in 2017. 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, CENTRAL, MEDLINE, PubMed, Embase, Google Scholar, OpenGrey, LILACS, and two trials registers from inception to 5 September 2022. We searched the bibliographies of all relevant studies, and contacted experts in the field for any additional trials. 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, 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, assessed the risk of bias in the included studies, and assessed the certainty of the evidence for each outcome. We resolved disagreements by discussion or by deferring to a third review author. When study details were missing, review authors contacted the study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. MAIN RESULTS: We included seven RCTs, in which a total of 387 women took part. In the comparison, Metformin plus megestrol versus megestrol alone, we rated the certainty of the evidence as low for the outcome, regression of endometrial hyperplasia. We rated the quality of the evidence as very low for the rest of the outcomes, in all three comparisons. Although there was a low risk of selection bias, there was a high risk of bias in the blinding of personnel and outcome assessment (performance bias and detection bias) in many studies. This update identified four new RCTs and six ongoing RCTs. Metformin versus megestrol We are uncertain whether metformin increases the regression of endometrial hyperplasia towards normal histology over megestrol (odds ratio (OR) 4.89, 95% confidence interval (CI) 1.56 to 15.32; P = 0.006; 2 RCTs, 83 participants; I² = 7%; very low-certainty evidence). This evidence suggests that if the rate of regression with megestrol is 61%, the rate of regression with metformin would be between 71% and 96%. It is unresolved whether metformin results in different rates of abnormal uterine bleeding or hysterectomy compared to megestrol. No study in this comparison reported progression of hyperplasia to endometrial cancer, recurrence of endometrial hyperplasia, health-related quality of life, or adverse effects during treatment. Metformin plus megestrol versus megestrol monotherapy The combination of metformin and megestrol may enhance the regression of endometrial hyperplasia towards normal histology more than megestrol alone (OR 3.27, 95% CI 1.65 to 6.51; P = 0.0007; 4 RCTs, 258 participants; I² = 0%, low-certainty evidence). This suggests that if the rate of regression with megestrol monotherapy is 54%, the rate of regression with the addition of metformin would be between 66% and 84%. In one study, 3/8 (37.5%) of participants who took metformin had nausea that settled without further treatment. It is unresolved whether the combination of metformin and megestrol results in different rates of recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, or hysterectomy compared to megestrol monotherapy. No study in this comparison reported abnormal uterine bleeding, or health-related quality of life. Metformin plus levonorgestrel (intrauterine system) versus levonorgestrel (intrauterine system) monotherapy We are uncertain whether there is a difference between groups in the regression of endometrial hyperplasia towards normal histology (OR 0.29, 95% CI 0.01 to 7.56; 1 RCT, 46 participants; very low-certainty evidence). This evidence suggests that if the rate of regression with levonorgestrel monotherapy is 96%, the rate of regression with the addition of metformin would be between 73% and 100%. It is unresolved whether the combination of metformin and levonorgestrel results in different rates of abnormal uterine bleeding, hysterectomy, or the development of adverse effects during treatment compared to levonorgestrel monotherapy. No study in this comparison reported recurrence of endometrial hyperplasia, progression of hyperplasia to endometrial cancer, or health-related quality of life. AUTHORS' CONCLUSIONS: Review authors found insufficient evidence to either support or refute the use of metformin, specifically megestrol acetate, given alone or in combination with standard therapy, for the treatment of women with endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials, yielding long-term outcome data are still needed to address this clinical question.

A scoping review of the literature on the impact of the COVID-19 quarantine on the psychological wellbeing of medical students.

BACKGROUND: The goal of this study was to identify the nature and extent of the available published research on the impact of social isolation, on the psychological wellbeing of medical students, who had to quarantine due to the COVID-19 pandemic. METHODS: Design. Scoping review. SEARCH STRATEGY: The PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews), guideline, was used to structure this study. A search strategy was carried out across six bibliographic databases. PubMed, Embase, ERIC, Scopus, Cochrane Database of Systematic Reviews and Web of Science. The following search terms were used, "medical student*" AND "impact" AND "quarantine" AND "COVID-19". Searches were initially confined to articles published (excluding conference abstracts) between 1 January 2019- 21 August 2021 but updated in September 2022 with the original search terms expanded to include "isolation" or "lockdown" as well as "quarantine" and the period of search extended to 21 August 2022. A search of secondary references was conducted. Data from the selected studies were extracted, and the following variables recorded; first author and year of publication, country of study, study design, sample size, participants, mode of analysing impact of quarantine from COVID-19 on mental health and results of the studies. RESULTS: A total of 223 articles were identified in the original search in 2021 and 387 articles, in the updated search in 2022. Following the exclusion of duplicates and application of the agreed inclusion and exclusion criteria, 31 full-text articles were identified for the final review, most of which were cross sectional studies. Sample sizes ranged from 13 to 4193 students and most studies used a variety of self-administered questionnaires to measure psychological wellbeing. Overall, 26 of the 31 articles showed that quarantine had a negative impact on the psychological well-being of medical students. However, two studies showed no impact, and three studies showed an improvement. CONCLUSION: The evidence is growing. Quarantine because of the COVID-19 pandemic may have had a negative impact on the psychological wellbeing of medical students, but this is not certain. There is therefore a need for more studies to further evaluate this research question.

Coenzyme A Restriction as a Factor Underlying Pre-Eclampsia with Polycystic Ovary Syndrome as a Risk Factor.

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.

Vibrational Biospectroscopy: An Alternative Approach to Endometrial Cancer Diagnosis and Screening.

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.

The student is key: A realist review of educational interventions to develop analytical and non-analytical clinical reasoning ability.

OBJECTIVES: 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. The aim of this study is 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: A total of 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. CONCLUSIONS: 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 amongst 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.

Lipidomic Biomarkers in Polycystic Ovary Syndrome and Endometrial Cancer.

Women with polycystic ovary syndrome (PCOS) are more likely to develop endometrial cancer (EC). The molecular mechanisms which increase the risk of EC in PCOS are unclear. Derangements in lipid metabolism are associated with EC, but there have been no studies, investigating if this might increase the risk of EC in PCOS. This was a cross-sectional study of 102 women in three groups of 34 (PCOS, EC and controls) at Nottingham University Hospital, UK. All participants had clinical assessments, followed by obtaining plasma and endometrial tissue samples. Lipidomic analyses were performed using liquid chromatography (LC) coupled with high resolution mass spectrometry (HRMS) and the obtained lipid datasets were screened using standard software and databases. Using multivariate data analysis, there were no common markers found for EC and PCOS. However, on univariate analyses, both PCOS and EC endometrial tissue samples showed a significant decrease in monoacylglycerol 24:0 and capric acid compared to controls. Further studies are required to validate these findings and investigate the potential role of monoacylglycerol 24:0 and capric acid in the link between PCOS with EC.

Correction to: A systematic review of the literature describing the outcomes of near-peer mentoring programs for first year medical students.

Following publication of the original article [1], the author reported incorrect referencing in Table 1 as the references of the papers in the table don't match with the text.

A systematic review of the literature describing the outcomes of near-peer mentoring programs for first year medical students.

BACKGROUND: Transition into higher education has been identified as one of the most stressful periods for learners. Interventions targeting the transition phase such as near- peer mentoring might help address some of these challenges. We were however unable to identify a published systematic review of the literature describing outcomes of near-peer mentoring of medical students during the transition phase into medical school. The aim of this paper is to review the literature and describe the outcomes of near-peer mentoring schemes for first-year medical students in the transition phase. METHODS: A search of different electronic databases was carried out, using the search terms peer, buddy, mentor*, counsel*, advise*, tutor*, student, medical, school. 1861 articles were identified, however only 5 studies met the inclusion criteria- primary mentees should be first-years, and mentors must be inclusive of second-years but not limited to them. In reporting this paper, the PRISMA guidelines were followed. RESULTS: Published material on near-peer mentoring for medical students is scarce. Three outcomes for peer mentoring were identified- professional and personal development, stress reduction, and ease of transitioning. Incidentally, peer-mentoring was also found to have facilitated the development of personal and professional attitudes in the mentors. The quality of the evaluation methods in the studies was however low to moderate. CONCLUSION: Near-peer-mentoring is a way of promoting professional and personal development. It is also promising to aid transition and maintain well-being of first-year medical students. However, larger, better quality longitudinal studies, are needed to ascertain its true value for these students.

Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome.

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 < .0001). CONCLUSIONS: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.

Metformin for endometrial hyperplasia.

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.

Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer.

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 < 0.0001). Sterol regulatory element binding protein-1 gene expression was positively correlated with body mass index (r = 0.017, p = 0.921) and waist-hip ratio (r = 0.023, p = 0.544) in polycystic ovary syndrome, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial sterol regulatory element binding protein-1 gene expression and body mass index in endometrial cancer (r = 0.643, p = 0.06) and waist-hip ratio (r = 0.096, p = 0.073). Sterol regulatory element binding protein-1 gene expression was significantly positively correlated with triglyceride in both polycystic ovary syndrome and endometrial cancer (p = 0.028 and p = 0.027, respectively). Quantitative serum sterol regulatory element binding protein-1 gene correlated with endometrial gene expression (p < 0.05). CONCLUSIONS: Sterol regulatory element binding protein-1 gene expression is significantly increased in the endometrium of women with polycystic ovary syndrome and women with endometrial cancer compared with controls and positively correlates with serum triglyceride in both polycystic ovary syndrome and endometrial cancer.

Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration.

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, ß 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, ß 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 INTERESTS: No financial support was obtained for this project. There are no conflicts of interest.

The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome--a proof-of-concept study.

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.

Preventing endometrial cancer risk in polycystic ovarian syndrome (PCOS) women: could metformin help?

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.

Validation of proteomic biomarkers previously found to be differentially expressed in women with polycystic ovary syndrome: a cross-sectional study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evaluating the impact of the reconfiguration of gynaecology services at a University Hospital NHS trust in the United Kingdom.

BACKGROUND: The project aim was to investigate the impact of reconfiguring gynaecology services on the key performance indicators of a University Hospital NHS Trust in the UK. The reconfiguration involved the centralisation of elective gynaecology on one hospital site and emergency gynaecology on the other. METHODS: Data measuring outcomes of the Trust's performance indicators (clinical outcomes, patient experience, staff satisfaction, teaching/training, research/development and value for money) were collected. Two time periods, 12 months before and after the reconfiguration in March 2011, were compared for all outcome measures except patient experience. Retrospective data from the hospitals audit department on clinical activity/outcomes and emergency gynaecology patient's feedback questionnaires were analysed. Staff satisfaction, teaching/training and research/development were measured through an online survey of gynaecology consultants. RESULTS: Post reconfiguration, the total number of admissions reduced by 6% (6,867 vs 6,446). There was a 14% increase in elective theatre sessions available (902.29 vs 1030.57) and an 84% increase in elective theatre sessions cancelled (44.43 vs 81.71). However, the average number of elective operations performed during each theatre session remained similar (2.63 vs 2.5). There was a significant increase in medical devices related clinical incidents (2 vs 11). With patient experience, there was a significant reduction in patient's overall length of stay on the emergency gynaecology ward and waiting times for investigations. For staff satisfaction, Consultants were significantly more dissatisfied with workload (3.45 vs 2.85) and standards of care (3.75 vs 2.93). With research and development, consultants remained dissatisfied with time/funding/opportunities for research. No significant impact on undergraduate/postgraduate teaching was found. No financial data on gynaecology was provided for the assessment of value for money. CONCLUSIONS: Reconfiguration of gynaecology services at this Trust may have resulted in a reduction in gynaecological activity and increased cancellation of elective operations but did not significantly reduce the number of elective operations performed. Although consultants expressed increased dissatisfaction with standards of clinical care, clinical incident reports did not significantly increase apart from medical devices incidents. Patient experience of emergency gynaecology services was improved. This manuscript provides a framework for similar exercises evaluating the impact of service redesign in the NHS.

Evaluating an obstetrics and gynecology teaching program for medical students incorporating simulation-based education underpinned by cognitive load theory.

Although there have been previous publications on curriculum innovations in teaching O&G to medical students, especially utilizing simulation-based education, there have been none, as far as we know, incorporating and evaluating the outcomes using cognitive load theory. The aim of this article was to describe the introduction, implementation, and evaluation of an innovative teaching program in O&G, incorporating simulation-based education, underpinned by cognitive load theory. Cognitive load is defined as the amount of information a working memory can hold at any one time and incorporates three types of cognitive load-intrinsic, extraneous, and germane. To optimize learning, educators are encouraged to manage intrinsic cognitive load, minimize extraneous cognitive load, and promote germane cognitive load. In these sessions, students were encouraged to prepare in advance of each session with recommended reading materials; to limit intrinsic cognitive load and promote germane cognitive load, faculty were advised ahead of each session to manage intrinsic cognitive load, an open-book MCQ practice session aimed to reduce anxiety, promote psychological safety, and minimize extraneous cognitive load. For the simulation sessions, the faculty initially demonstrated the role-play situation or clinical skill first, to manage intrinsic cognitive load and reduce extraneous cognitive load. The results of the evaluation showed that the students perceived that they invested relatively low mental effort in understanding the topics, theories, concepts, and definitions discussed during the sessions. There was a low extraneous cognitive load. Measures of germane cognitive load or self-perceived learning were high. The primary message is that we believe this teaching program is a model that other medical schools globally might want to consider adopting, to evaluate and justify innovations in the teaching of O&G to medical students. The secondary message is that evaluation of innovations to teaching and facilitation of learning using cognitive load theory is one way to contribute to the high-quality training of competent future healthcare workers required to provide the highest standard of care to women who are crucial to the overall health and wellbeing of a nation.

Prevalence of pre-eclampsia in women in the Middle East: a scoping review.

Hypertensive disorders of pregnancy are the second most common cause of maternal deaths worldwide. Metabolic syndrome is recognized as one of the risk factors for pre-eclampsia. A recent study revealed a high prevalence of metabolic syndrome in the United Arab Emirates (UAE), particularly amongst Emirati women compared with global estimates. This finding raises the possibility that the prevalence of pre-eclampsia in the region may also be higher as research is increasingly demonstrating an association between pre-eclampsia and metabolic syndrome. We therefore conducted this scoping review of the literature to investigate the nature and extent of studies evaluating the prevalence of pre-eclampsia within the Middle East region to enable subsequent comparison of these findings with the global burden of pre-eclampsia, objectively identify gaps in the literature and inform the design of future studies to address these gaps. PubMed and Scopus were used to extract studies published over the last 20 years (2003-2023). The search terms used included ("Pre-eclampsia" AND "Prevalence") OR ("Hypertension in pregnancy" AND "Prevalence") OR ("Pregnancy" AND "Pre-eclampsia") OR ("Pre-eclampsia" AND "Epidemiology"). We limited our studies to those from the Middle East (ME). A total of 556 relevant articles were identified following which 11 were shortlisted for review. There were four studies from Iran, two from Saudi Arabia, two from Qatar, one from Jordan, and one from Bahrain. The remaining study included 29 countries from Africa, Asia, Latin America, and the Middle East of which data from Jordan, Lebanon, the Occupied Palestinian Territory, and Qatar were included. There were four retrospective, two cross-sectional, and two cohort studies, one prospective study, one meta-analysis, and one descriptive-analytical study. The prevalence of pre-eclampsia in the studies ranged from 0.17 to 5%. We did not find any study investigating the prevalence of pre-eclampsia in the United Arab Emirates. Based on our findings, we conclude that there is a significant scarcity of research in this area, especially within the Middle East, and notably an absence of studies specifically pertaining to the UAE. Consequently, we assert that there is a pressing requirement for additional research to evaluate the prevalence of pre-eclampsia in the region.

A common curriculum in obstetrics and gynecology for medical students globally.

OBJECTIVE: Global variations in women's health outcomes, increased international migration, and an increase in the number of medical schools underpin the need for global standardization in obstetrics and gynecology curricula for medical students. However, there are currently no recommendations regarding the content of a common curriculum. The aim of this project was to agree the objectives for a common curriculum in obstetrics and gynecology for medical students globally. METHODS: The curriculum was developed and agreed by an international taskforce of obstetricians and gynecologists. Published curricula for medical students in a variety of regions globally were reviewed and discussed, and the objectives for a common curriculum in obstetrics and gynecology for medical students were agreed by consensus. RESULTS: The content of the proposed curriculum is classified into three domains: clinical skills, professional behaviors, and knowledge. The recommended curriculum covers health conditions that affect women globally in different social and cultural contexts, and addresses important global health issues of relevance to obstetrics and gynecology. CONCLUSION: The methods and outcomes of a project by an international taskforce of obstetricians and gynecologists to develop a common curriculum in obstetrics and gynecology for medical students globally are presented. More work is required to identify ways in which the curriculum may be adapted to a minimum essential required curriculum in times of man-made or natural disasters. Achieving these will facilitate the intended long-term aims of this curriculum, to improve women's health outcomes globally.

Prevalence and Diagnosis of PCOS Using Electronic Health Records: A Scoping Review and a Database Analysis.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. It increases the risk of type 2 diabetes, cardiovascular disease, endometrial cancer, infertility, gestational diabetes, preeclampsia, and preterm birth. Accurately identifying predictors of these health risks is crucial. Electronic health records (EHRs) offer an affordable approach, however, the validity and reliability of EHRs for PCOS diagnosis are unclear. A scoping review of the literature on the prevalence and reliability of the diagnosis of PCOS using EHRs was performed. An analysis of the feasibility of obtaining diagnostic variables from a PCOS patient database was also carried out. Eight studies met the criteria. The prevalence of PCOS ranged from 0.27% to 5.8%. Reliability varied, with one study reporting a sensitivity of 50% and a specificity of 29%. Another study found a 74.4% agreement between international classification of disease (ICD) codes and clinical criteria. The database analysis found only 13.7%, 8%, and 7.5% of women had all the necessary variables for an objective diagnosis of PCOS using the Rotterdam, National Institutes of Health (NIH), and Androgen Excess and PCOS Society (AEPCOS) criteria, respectively. Using EHRs results in an underestimation of PCOS prevalence compared to other diagnostic criteria, and many women identified may not meet the complete diagnostic criteria. These findings have implications for future research studies on PCOS prevalence and related health risks.