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Introduction: Polycystic ovarian syndrome (PCOS) is the commonest endocrine condition affecting reproductive age women. Many biomarkers may aid assessment and management, however evidence is limited on their utility in clinical practice. We conducted a review of systematic reviews to identify the most useful biomarkers in the clinical management of PCOS. Methods: We searched MEDLINE, EMBASE, CENTRAL and HTA until August 2023 for reviews evaluating biomarkers in PCOS women compared to healthy controls. Methodological quality was assessed using the AMSTAR2 tool. We reported pooled evidence for each biomarker with 95% confidence intervals from the most recent, up‐to‐date, and best quality review. Results: From 3360 citations, we included 75 systematic reviews (88 biomarkers, 191,792 women). Most reviews (50/75, 67%) were moderate quality, but reported high heterogeneity (66/75, 88%). We identified 63 abnormal biomarkers in women with PCOS versus healthy controls. Of these, 22 core biomarkers could help evaluate the multisystemic impact of PCOS and inform patient management and surveillance: dehydroepiandrosterone, prolactin, sex hormone‐binding globulin, total and free testosterone, anti‐Mullerian hormone, systolic and diastolic blood pressure, c‐reactive protein, fibrinogen, oral glucose tolerance test, homoeostatic model assessment‐insulin resistance index, fasting insulin, total cholesterol, triglycerides, lipoprotein(a), HDL, LDL, non‐HDL‐cholesterol, ferritin, iron, and 25‐hydroxy‐vitamin D. Conclusion: We identified 22 core biomarkers assessing the multisystemic impact of PCOS and inform its clinical management. Future research is required to establish validated healthcare pathways. [ABSTRACT FROM AUTHOR]

Background and Objective: Functional magnetic resonance imaging, in conjunction with models of peripheral and/or central sensitization, has been used to assess analgesic efficacy in healthy humans. This review aims to summarize the use of these techniques to characterize brain mechanisms of hyperalgesia/allodynia and to evaluate the efficacy of analgesics. Databases and Data Treatment: Searches were performed (PubMed‐Medline, Cochrane, Web of Science and Clinicaltrials.gov) to identify and review studies. A co‐ordinate based meta‐analysis (CBMA) was conducted to quantify neural activity that was reported across multiple independent studies in the hyperalgesic condition compared to control, using GingerALE software. Results: Of 217 publications, 30 studies met the inclusion criteria. They studied nine different models of hyperalgesia/allodynia assessed in the primary (14) or secondary hyperalgesia zone (16). Twenty‐three studies focused on neural correlates of hyperalgesic conditions and showed consistent changes in the somatosensory cortex, prefrontal cortices, insular cortex, anterior cingulate cortex, thalamus and brainstem. The CBMA on 12 studies that reported activation coordinates for a contrast comparing the hyperalgesic state to control produced six activation clusters (significant at false discovery rate of 0.05) with more peaks for secondary (17.7) than primary zones (7.3). Seven studies showed modulation of brain activity by analgesics in five of the clusters but also in four additional regions. Conclusions: This meta‐analysis revealed substantial but incomplete overlap between brain areas related to neural mechanisms of hyperalgesia and those reflecting the efficacy of analgesic drugs. Studies testing in the secondary zone were more sensitive to evaluate analgesic efficacy on central sensitization at brainstem or thalamocortical levels. Significance: Experimental pain models that provide a surrogate for features of pathological pain conditions in healthy humans and functional imaging techniques are both highly valuable research tools. This review shows that when used together, they provide a wealth of information about brain activity during pain states and analgesia. These tools are promising candidates to help bridge the gap between animal and human studies, to improve translatability and provide opportunities for identification of new targets for back‐translation to animal studies. [ABSTRACT FROM AUTHOR]

Objective: Many women with Turner syndrome (TS) will consider fertility options and pregnancy. We wished to examine the fertility and pregnancy outcomes in women with TS undergoing oocyte donation (OD) treatment or spontaneous pregnancy in a large single‐centre cohort. General population reference data or data from those with idiopathic premature ovarian insufficiency were used as comparators. Design: A retrospective single‐centre cross‐sectional study. Patients and Measurements: Seventy‐four women with TS underwent OD treatment with a total of 105 pregnancies, and 31 women with TS had 71 spontaneous conceptions. Fertility outcomes included clinical pregnancy and live birth rate. Pregnancy outcomes included miscarriage rate, prevalence of hypertension, gestational diabetes, lower segment caesarean section (LSCS), small for gestational age (SGA), prematurity and vertical transmission of TS. Results: In those with TS, OD pregnancies were associated with increased rates of LSCS and SGA compared to spontaneous pregnancies; LSCS (OR: 4.19, 95% CI: 1.6−10.8, p =.003) and SGA (OR: 2.92, 95% CI: 1.02−8.38, p =.04). There were no recorded cardiac events but 5 (17.2%) cases of vertical transmissions of TS in daughters were identified. OD in those with TS was associated with a lower live birth rate per cycle started (OR: 0.53, 95% CI: 0.34−0.84, p =.008) and a higher rate of miscarriage compared to women with POI (40% vs. 26.2%, p =.04). Conclusions: We show that pregnancy in women with TS, whether OD or spontaneously conceived, carries obstetric risks, and therefore, women with TS, considering pregnancy, should receive comprehensive pre‐pregnancy counselling and optimal obstetric care. [ABSTRACT FROM AUTHOR]

Objective: Polycystic ovary syndrome (PCOS) is a chronic lifelong condition affecting up to 20% of women worldwide. There is limited input from affected women to guide the provision of healthcare services and future research needs. Our objective was to scope the healthcare and research priorities of women with PCOS in the United Kingdom. Design: A three‐staged modified Delphi method, consisting of two questionnaires and a consensus meeting involving lay representatives and healthcare professionals. Patients and Measurements: Lay patient representatives of women with PCOS. Participants were asked to identify and rank healthcare and research priorities for their importance. Results: Six hundred and twenty‐four lay participants took part in our Delphi method. Over 98% were diagnosed with PCOS (614/624, 98.4%). More than half experienced difficulties to receive a PCOS diagnosis (375/624, 60%), and the majority found it difficult to access specialised PCOS health services in the NHS (594/624, 95%). The top two healthcare priorities included better education for health professionals on the diagnosis and management of PCOS (238/273, 87.1%) and the need to set up specialist PCOS services (234/273, 85.7%). The top two research priorities focused on identifying better treatments for irregular periods (233/273, 85.3%) followed by better tests for early PCOS diagnosis (230/273, 84.2%). Conclusions: We identified 13 healthcare and 14 research priorities that reflect the current health needs of women with PCOS in the United Kingdom. Adopting these priorities in future healthcare and research planning will help to optimise the health of women with PCOS and increase patient satisfaction. [ABSTRACT FROM AUTHOR]

Based on our previous work, in which acute intravenous hormone infusion reduced food intake in healthy men,[11] a sample size of 16 people would have 90% power (at a significance level of 0.05) to detect a clinically significant reduction in food intake of 2.3 ± 1.3 kcal/kg. This is the first study to report on the effect of kisspeptin on appetite, food intake, glucose and insulin levels in women, and in people who are overweight or have obesity. Keywords: appetite control; experimental pharmacology; randomized trial; weight control EN appetite control experimental pharmacology randomized trial weight control 2393 2397 5 07/04/23 20230801 NES 230801 BACKGROUND Kisspeptin is recognized to have a critical role in the control of reproductive function[[1]]; however, as reproductive processes require adequate energy stores, there is increasing focus on its interaction with metabolic processes. (B) Luteinizing hormone (LH) levels were higher during kisspeptin infusion compared with vehicle infusion (**p < .01). gl Serum insulin, plasma glucose, serum luteinizing hormone (LH) and serum oestradiol were measured in the Clinical Chemistry Laboratory of Imperial College Healthcare NHS Trust. [Extracted from the article]

** denotes P <= 0.01 gl C-peptide levels and pre-existing diabetes C-peptide values at follow-up at least 3 months after initial presentation with COVID-19 compared with those without (median [IQR] C-peptide [pmol/L]: pre-existing diabetes 1550 [1285, 2638], no diabetes 1239 [675, 1622], I P i = .008) (Figure 1B). C-peptide and COVID-19 disease severity and management C-peptide levels were higher in those who had severe or critical disease compared with those with mild disease (median [IQR] C-peptide mild: 762 [510, 1289] pmol/L, severe/critical: 1538 [1143, 2906] pmol/L, I P i = .004) (Figure 1C). Hyperglycaemia1 and new diagnoses of diabetes (including autoantibody-negative type 1 diabetes2) have been reported in patients with coronavirus disease 2019 (COVID-19).1 Moreover, 77% of patients with COVID-19 and ketoacidosis (a condition typically associated with type 1 diabetes or pancreatic destruction) had type 2 diabetes.3 The receptor necessary for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, ACE2, and its permissive protein, TMPRSS2, are present in the pancreatic microvasculature4 and, at postmortem, SARS-CoV-2 viral RNA has been detected in pancreatic beta cells.5 In islets infected with SARS-CoV-2, in vitro insulin secretion, particularly glucose-stimulated insulin secretion, is attenuated.6 Given this, it has been speculated that insulin secretory capacity may be curtailed by direct cytopathic action of SARS-CoV-2 on beta cells. C-peptide is preserved at follow-up at >=3 months following presentation with COVID-19 At the study visit appointment, which took place at least 3 months after initial presentation with COVID-19, median (IQR) C-peptide was 1319 (849, 1905) pmol/L and no patients had undetectable C-peptide levels (<3.3 pmol/L). [Extracted from the article]

Given that long COVID is a complex, multi-system disorder, that remains little understood, larger long-term studies comparing patients diagnosed with COVID-19 and persistent symptoms, to those without, as well as healthy controls, might provide interesting insights into the prevalence of subtle perturbations in adrenal function. Keywords: adrenal cortex hormones; adrenal insufficiency; COVID-19; mineralocorticoids EN adrenal cortex hormones adrenal insufficiency COVID-19 mineralocorticoids 270 272 3 01/03/23 20230201 NES 230201 It is widely recognised that the effects of COVID-19 extend beyond the respiratory system. Letter to the editor of clinical endocrinology: Assessment of adrenal function in patients who survive COVID-19. [Extracted from the article]

Background: Secondary oligo/amenorrhoea occurs in 3%–5% of women of reproductive age. The two most common causes are polycystic ovary syndrome (PCOS) (2%–13%) and functional hypothalamic amenorrhoea (FHA) (1%–2%). Whilst both conditions have distinct pathophysiology and their diagnosis is supported by guidelines, in practice, differentiating these two common causes of menstrual disturbance is challenging. Moreover, both diagnoses are qualified by the need to first exclude other causes of menstrual disturbance. Aim: To review clinical, biochemical and radiological parameters that could aid the clinician in distinguishing PCOS and FHA as a cause of menstrual disturbance. Results: FHA is uncommon in women with BMI > 24 kg/m2, whereas both PCOS and FHA can occur in women with lower BMIs. AMH levels are markedly elevated in PCOS; however, milder increases may also be observed in FHA. Likewise, polycystic ovarian morphology (PCOM) is more frequently observed in FHA than in healthy women. Features that are differentially altered between PCOS and FHA include LH, androgen, insulin, AMH and SHBG levels, endometrial thickness and cortisol response to CRH. Other promising diagnostic tests with the potential to distinguish these two conditions pending further study include assessment of 5‐alpha‐reductase activity, leptin, INSL3, kisspeptin and inhibin B levels. Conclusion: Further data directly comparing the discriminatory potential of these markers to differentiate PCOS and FHA in women with secondary amenorrhoea would be of value in defining an objective probability for PCOS or FHA diagnosis. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans. Materials and methods: In 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m−2), we compared the effects of 1 nmol kg−1 h−1 kisspeptin versus vehicle administration on glucose‐stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose‐stimulated insulin secretion in vitro in human pancreatic islets and a human β‐cell line (EndoC‐βH1 cells). Results: Kisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose‐stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men. Conclusions: Collectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin‐based therapies for reproductive and potentially metabolic conditions. [ABSTRACT FROM AUTHOR]

Objective Anaemia is frequently found in patients with diabetes, in whom it is associated with increased morbidity and mortality. Low testosterone levels are also common in men with type 2 diabetes. We hypothesized that low testosterone levels are also associated with anaemia in men with type 2 diabetes, over the effects of chronic kidney disease. Design Cross-sectional cohort study, performed in 2005 in a tertiary diabetes clinic. Patients 464 men with type 2 diabetes. Main outcome measure Anaemia (haemoglobin (Hb) < 13·7 g/dl in men aged < 60, or < 13·2 g/dl in men aged 60 and older). Results About 24% of study participants had anaemia, which was associated with the presence and severity of chronic kidney disease, systemic inflammation, increased age, and reduced iron availability. In addition, testosterone levels were independently associated with reduced Hb levels, determining between 6 and 8% of the total variability in raw Hb levels in this population after adjusting for these other factors. Individuals with total testosterone level < 10 nmol/l (43% of the cohort) were more likely to have anaemia (adjusted odds ratio 1·7; 95% CI 1·1–2·8). Similarly, anaemia was twice as common in individuals with a calculated free testosterone of < 0·23 nmol/l (adjusted odds ratio 2·0, 95% CI 1·2–3·1). Conclusions These findings suggest that testosterone deficiency may contribute to the increased frequency of anaemia in men with type 2 diabetes. However, the appropriate clinical response to testosterone deficiency in anaemic patients remains to be established by prospective clinical trials. [ABSTRACT FROM AUTHOR]

Learning health systems (LHS) use digital health and care data to improve care, shorten the timeframe of improvement projects, and ensure these are based on real‐world data. In the United Kingdom, policymakers are depending on digital innovation, driven by better use of data about current health service performance, to enable service transformation and a more sustainable health system. This paper examines what would be needed to develop LHS in the United Kingdom, considering national policy implications and actions, which local organisations and health systems could take. The paper draws on a seminar attended by academics, policymakers, and practitioners, a brief literature review, and feedback from policy experts and National Health Service (NHS) stakeholders. Although there are examples of some aspects of LHS in the UK NHS, it is hard to find examples where there is a continuous cycle of improvement driven by information and where analysis of data and implementing improvements is part of usual ways of working. The seminar and literature identified a number of barriers. Incentives and capacity to develop LHS are limited, and requires a shift in analytic capacity from regulation and performance, to quality improvement and transformation. The balance in priority given to research compared with implementation also needs to change. Policy initiatives are underway which address some barriers, including building analytical capacity, developing infrastructure, and data standards. The NHS and research partners are investing in infrastructure which could support LHS, although clinical buy in is needed to bring about improvement or address operational challenges. We identify a number of opportunities for local NHS organisations and systems to make better use of health data, and for ways that national policy could promote the collaboration and greater use of analytics which underpin the LHS concept. [ABSTRACT FROM AUTHOR]