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Background: Activin A is a potent negative regulator of muscle mass elevated in critical illness. It is unclear whether muscle strength and physical function in critically ill humans are associated with elevated activin A levels., Objectives: The objective of this study was to investigate the relationship between serum activin A levels, muscle strength, and physical function at discharge from the intensive care unit (ICU) and hospital., Methods: Thirty-six participants were recruited from two tertiary ICUs in Melbourne, Australia. Participants were included if they were mechanically ventilated for >48 h and expected to have a total ICU stay of >5 days. The primary outcome measure was the Six-Minute Walk Test distance at hospital discharge. Secondary outcome measures included handgrip strength, Medical Research Council Sum Score, Physical Function ICU Test Scored, Six-Minute Walk Test, and Timed Up and Go Test assessed throughout the hospital admission. Total serum activin A levels were measured daily in the ICU., Results: High peak activin A was associated with worse Six-Minute Walk Test distance at hospital discharge (linear regression coefficient, 95% confidence interval, p-value: -91.3, -154.2 to -28.4, p = 0.007, respectively). Peak activin A concentration was not associated with the secondary outcome measures., Conclusions: Higher peak activin A may be associated with the functional decline of critically ill patients. Further research is indicated to examine its potential as a therapeutic target and a prospective predictor for muscle wasting in critical illness., Study Registration: ACTRN12615000047594., (Copyright © 2022 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Women with PCOS have substantially greater symptoms of depression and anxiety, and a lower health-related quality of life (HRQoL) compared to women without PCOS. The aim of this study was to determine if high-intensity interval training (HIIT) could provide greater improvements in mental health outcomes than standard moderate-intensity continuous training (MICT). Twenty-nine overweight women with PCOS aged 18-45 years were randomly assigned to 12 weeks of either MICT (60-75% HR peak , N = 15) or HIIT (> 90% HR peak , N = 14). Outcome measures included symptoms of depression, anxiety and stress (DASS-21), general HRQoL (SF-36) and PCOS specific HRQoL (PCOSQ) collected at baseline and post-intervention. Reductions in depression (Δ - 1.7, P = 0.005), anxiety (Δ - 3.4, P < 0.001) and stress (Δ - 2.4, P = 0.003) scores were observed in the HIIT group, while MICT only resulted in a reduction in stress scores (Δ - 2.9, P = 0.001). Reductions in anxiety scores were significantly higher in the HIIT group compared to the MICT group (β = - 2.24, P = 0.020). Both HIIT and MICT significantly improved multiple domain scores from the SF-36 and PCOSQ. This study highlights the potential of HIIT for improving mental health and HRQoL in overweight women with PCOS. HIIT may be a viable strategy to reduce symptoms of depression and anxiety in women with PCOS, however, large-scale studies are required to confirm these findings.Trial registration number: ACTRN12615000242527., (© 2023. The Author(s).)

Background: Women with polycystic ovary syndrome (PCOS) experience general and PCOS-specific barriers that limit their engagement with exercise and contribute to high attrition from exercise programs, hindering the potential benefits of exercise to address their increased cardio-metabolic risk. A positive remembered affective response can predict future intentions and adherence to exercise prescription., Objectives: To compare the longitudinal changes in remembered affect to high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) in women with PCOS and to determine whether longitudinal changes in remembered affect are correlated with changes in fitness, body mass index, adherence and exercise enjoyment., Methods: Physically inactive, overweight women with PCOS were randomly assigned to 12 weeks of either HIIT (n = 15) or MICT (n = 14) (3 sessions per week). Remembered affective valence (Feeling Scale) was collected after each exercise session. Cardiorespiratory fitness (VO 2peak ) was assessed at baseline and post-intervention. Exercise enjoyment was assessed post-intervention., Results: The longitudinal changes in the remembered affect were more positive in the HIIT group compared to MICT (β = 0.017, p = 0.047). HIIT was also considered more enjoyable than MICT (p = 0.002). Adherence was high in both groups (>90%). We found a moderate correlation with longitudinal changes between the remembered affect and change in fitness (r s  = 0.398) and exercise enjoyment (r s  = 0.376) using the combined group, however, these were not statistically significant (p = 0.054 and p = 0.064, respectively)., Conclusions: HIIT demonstrated a more positive longitudinal remembered affective response and greater exercise enjoyment compared to MICT in overweight women with PCOS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a common endocrine condition characterised by a range of reproductive, endocrine, metabolic and psychological abnormalities. Reports estimate that around 10% of women of reproductive age are affected by PCOS, representing a significant prevalence worldwide, which poses a high economic health burden. As the origin of PCOS remains largely unknown, there is neither a cure nor mechanism-based treatments leaving patient management suboptimal and focused solely on symptomatic treatment. However, if the underlying mechanisms underpinning the development of PCOS were uncovered then this would pave the way for the development of new interventions for PCOS. Recently, there have been significant advances in our understanding of the underlying pathways likely involved in PCOS pathogenesis. Key insights include the potential involvement of androgens, insulin, anti-Müllerian hormone and transforming growth factor beta in the development of PCOS. This review will summarise the significant scientific discoveries on these factors that have enhanced our knowledge of the mechanisms involved in the development of PCOS and discuss the impact these insights may have in shaping the future development of effective strategies for women with PCOS.

Polycystic ovary syndrome (PCOS) is characterised by a hormonal imbalance affecting the reproductive and metabolic health of reproductive-aged women. Exercise is recommended as a first-line therapy for women with PCOS to improve their overall health; however, women with PCOS are resistant to the metabolic benefits of exercise training. Here, we aimed to gain insight into the mechanisms responsible for such resistance to exercise in PCOS. We employed an in vitro approach with electrical pulse stimulation (EPS) of cultured skeletal muscle cells to explore whether myotubes from women with PCOS have an altered gene expression signature in response to contraction. Following EPS, 4719 genes were differentially expressed (false discovery rate <0.05) in myotubes from women with PCOS compared to 173 in healthy women. Both groups included genes involved in skeletal muscle contraction. We also determined the effect of two transforming growth factor β (TGFβ) ligands that are elevated in plasma of women with PCOS, TGFβ1 and anti-Müllerian hormone (AMH), alone and on the EPS-induced response. While AMH (30 ng/ml) had no effect, TGFβ1 (5 ng/ml) induced the expression of extracellular matrix genes and impaired the exercise-like transcriptional signature in myotubes from women with and without PCOS in response to EPS by interfering with key processes related to muscle contraction, calcium transport and actin filament. Our findings suggest that while the fundamental gene expression responses of skeletal muscle to contraction is intact in PCOS, circulating factors like TGFβ1 may be responsible for the impaired adaptation to exercise in women with PCOS. KEY POINTS: Gene expression responses to in vitro contraction (electrical pulse stimulation, EPS) are altered in myotubes from women with polycystic ovary syndrome (PCOS) compared to healthy controls, with an increased expression of genes related to pro-inflammatory pathways. Transforming growth factor β1 (TGFβ1) upregulates genes related to extracellular matrix remodelling and reduces the expression of contractile genes in myotubes, regardless of the donor's health status. TGFβ1 alters the gene expression response to EPS, providing a possible mechanism for the impaired exercise adaptations in women with PCOS., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Study Question: Does 12 weeks of high-intensity interval training (HIIT) result in greater improvements in cardio-metabolic and reproductive outcomes compared to standard moderate-intensity continuous training (MICT) in women with polycystic ovary syndrome (PCOS)?, Summary Answer: HIIT offers greater improvements in aerobic capacity, insulin sensitivity and menstrual cyclicity, and larger reductions in hyperandrogenism compared to MICT., What Is Known Already: Exercise training is recognized to improve clinical outcomes in women with PCOS, but little is known about whether HIIT results in greater health outcomes compared to standard MICT., Study Design, Size, Duration: This was a two-armed randomized clinical trial enrolling a total of 29 overweight women with PCOS between May 2016 and November 2019., Participants/materials, Setting, Methods: Women with PCOS aged 18-45 years were randomly assigned to 12 weeks of either MICT (60-75% peak heart rate, N = 14) or HIIT (>90% peak heart rate, N = 15), each completed three times per week. The primary clinical outcomes were aerobic capacity (VO2peak) and insulin sensitivity (euglycaemic-hyperinsulinaemic clamp). Secondary outcomes included hormonal profiles, menstrual cyclicity and body composition., Main Results and the Role of Chance: Both HIIT and MICT improved VO2peak (HIIT; Δ 5.8 ± 2.6 ml/kg/min, P < 0.001 and MICT; Δ 3.2 ± 2 ml/kg/min, P < 0.001), however, the HIIT group had a greater improvement in aerobic capacity compared to MICT (β = 2.73 ml/kg/min, P = 0.015). HIIT increased the insulin sensitivity index compared to baseline (Δ 2.3 ± 4.4 AU, P = 0.007) and MICT (β = 0.36 AU, P = 0.030), and caused higher increases in sex hormone-binding globulin compared to MICT (β = 0.25 nmol/l, P = 0.002). HIIT participants were 7.8 times more likely to report improved menstrual cyclicity than those in the MICT group (odds ratio 7.8, P = 0.04)., Limitations, Reasons for Caution: This study has a small sample size and the findings of the effect of the exercise interventions are limited to overweight reproductive-aged women, who do not have any co-existing co-morbidities that require medication., Wider Implications of the Findings: Exercise, regardless of intensity, has clear health benefits for women with PCOS. HIIT appears to be a more beneficial strategy and should be considered for promoting health and reducing cardio-metabolic risk in overweight women with PCOS., Study Funding/competing Interest(s): This work was supported by a Project Support Grant from the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in PCOS. The authors have no conflicts of interest to disclose., Trial Registration Number: ACTRN12615000242527., Trial Registration Date: 19 February 2015., Date of First Patient’s Enrolment: 27 May 2016., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Polycystic ovary syndrome (PCOS) is a complex condition, impacting cardio-metabolic and reproductive health, mental health and health-related quality of life. The physical health benefits of exercise for women with PCOS are well-established and exercise is increasingly being recognised as efficacious for improving psychological wellbeing. The aim of this review was to summarise the evidence regarding the effectiveness of exercise interventions on mental health outcomes in women with PCOS., Methods: A systematic search of electronic databases was conducted in March of 2020. Trials that evaluated the effect of an exercise intervention on mental health or health-related quality of life outcomes in reproductive aged women with diagnosed PCOS were included. Methodological quality was assessed using the modified Downs and Black checklist. Primary outcomes included symptoms of depression and anxiety, and health-related quality of life., Results: Fifteen articles from 11 trials were identified and deemed eligible for inclusion. Exercise demonstrated positive improvements in health-related quality of life in all of the included studies. Half of included studies also reported significant improvements in depression and anxiety symptoms. There was large variation in methodological quality of included studies and in the interventions utilised., Conclusions: The available evidence indicates that exercise is effective for improving health-related quality of life and PCOS symptom distress. Exercise also shows some efficacy for improving symptoms and/or prevalence of depression and anxiety in women with PCOS. However, due to large heterogeneity of included studies, conclusions could not be made regarding the impact of exercise intervention characteristics. High-quality trials with well reported exercise intervention characteristics and outcomes are required in order to determine effective exercise protocols for women with PCOS and facilitate translation into practice., (© 2021. The Author(s).)

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance and impaired energy metabolism in skeletal muscle, the aetiology of which is currently unclear. Here, we mapped the gene expression profile of skeletal muscle from women with PCOS and determined if cultured primary myotubes retain the gene expression signature of PCOS in vivo. Transcriptomic analysis of vastus lateralis biopsies collected from PCOS women showed lower expression of genes associated with mitochondrial function, while the expression of genes associated with the extracellular matrix was higher compared to controls. Altered skeletal muscle mRNA expression of mitochondrial-associated genes in PCOS was associated with lower protein expression of mitochondrial complex II-V, but not complex I, with no difference in mitochondrial DNA content. Transcriptomic analysis of primary myotube cultures established from biopsies did not display any differentially expressed genes between controls and PCOS. Comparison of gene expression profiles in skeletal muscle biopsies and primary myotube cultures showed lower expression of mitochondrial and energy metabolism-related genes in vitro, irrespective of the group. Together, our results show that the altered mitochondrial-associated gene expression in skeletal muscle in PCOS is not preserved in cultured myotubes, indicating that the in vivo extracellular milieu, rather than genetic or epigenetic factors, may drive this alteration. Dysregulation of mitochondrial-associated genes in skeletal muscle by extracellular factors may contribute to the impaired energy metabolism associated with PCOS.

Women with polycystic ovary syndrome (PCOS), commonly have profound skeletal muscle insulin resistance which can worsen other clinical features. The heterogeneity of the condition has made it challenging to identify the precise mechanisms that cause this insulin resistance. A possible explanation for the underlying insulin resistance may be the dysregulation of Transforming Growth Factor-beta (TGFβ) signalling. TGFβ signalling contributes to the remodelling of reproductive and hepatic tissues in women with PCOS. Given the systemic nature of TGFβ signalling and its role in skeletal muscle homeostasis, it may be possible that these adverse effects extend to other peripheral tissues. We aimed to determine if TGFβ1 could negatively regulate glucose uptake and insulin signalling in skeletal muscle of women with PCOS. We show that both myotubes from women with PCOS and healthy women displayed an increase in glucose uptake, independent of changes in insulin signalling, following short term (16 hr) TGFβ1 treatment. This increase occurred despite pro-fibrotic signalling increasing via SMAD3 and connective tissue growth factor in both groups following treatment with TGFβ1. Collectively, our findings show that short-term treatment with TGFβ1 does not appear to influence insulin signalling or promote insulin resistance in myotubes. These findings suggest that aberrant TGFβ signalling is unlikely to directly contribute to skeletal muscle insulin resistance in women with PCOS in the short term but does not rule out indirect or longer-term effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 McIlvenna, Patten, McAinch, Rodgers, Stepto and Moreno-Asso.)

Exercise can improve mental health; however many tertiary students do not reach recommended levels of weekly engagement. Short-term exercise may be more achievable for tertiary students to engage in to promote mental health, particularly during times of high stress. The current scoping review aimed to provide an overview of controlled trials testing the effect of short-term (single bout and up to 3 weeks) exercise across mental health domains, both at rest and in response to an experimentally manipulated laboratory stress task, in tertiary students. The search was conducted using 'Evidence Finder,' a database of published and systematic reviews and controlled trials of interventions in the youth mental health field. A total of 14 trials meet inclusion criteria, six measured mental health symptoms in response to an experimentally manipulated laboratory stress task and the remaining eight measured mental health symptoms. We found that short-term exercise interventions appeared to reduce anxiety like symptoms and anxiety sensitivity and buffered against a drop in mood following an experimentally manipulated laboratory stress task. There was limited available evidence testing the impacts of exercise on depression like symptoms and other mental health mental health domains, suggesting further work is required. Universities should consider implementing methods to increase student knowledge about the relationship between physical exercise and mental health and student access to exercise facilities., (© 2021. The Author(s).)

Aim: To describe the quality and completeness of the description and reporting of physical activity and exercise interventions delivered to young people to promote mental health or treat mental illness., Methods: We conducted a series of scoping reviews identifying 64 controlled trials of physical activity and exercise interventions delivered to young people. We extracted: intervention characteristics, personnel and delivery format, the intensity, duration, frequency and type of physical activity or exercise., Results: There was limited reporting of intervention details across studies; 52% did not provide information to confidently assess intervention intensity, 29% did not state who delivered the intervention, and 44% did not specify the intervention delivery format., Conclusions: We recommend that authors adhere to the CONSORT reporting requirements and its intervention reporting extensions, (a) the Template for Intervention Description and Replication, (b) Consensus for Exercise Reporting Template and (c) as part of this, detail the frequency, intensity, time and type of physical activity recommendations and prescriptions. Without this, future trials are unable to replicate and extend previous work to support or disconfirm existing knowledge, leading to research waste and diminishing translation and implementation potential., (© 2020 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Aim: We investigated whether acute carbohydrate ingestion reduced arterial potassium concentration ([K + ]) during and after intense exercise and delayed fatigue., Methods: In a randomized, double-blind crossover design, eight males ingested 300 ml water containing 75 g glucose (CHO) or placebo (CON); rested for 60 min, then performed high-intensity intermittent cycling (HIIC) at 130% V ˙ O 2peak , comprising three 45-s exercise bouts (EB), then a fourth EB until fatigue. Radial arterial (a) and antecubital venous (v) blood was sampled at rest, before, during and after HIIC and analyzed for plasma ions and metabolites, with forearm arteriovenous differences (a-v diff) calculated to assess inactive forearm muscle effects., Results: Glucose ingestion elevated [glucose] a and [insulin] a above CON (p = .001), being, respectively, ~2- and ~5-fold higher during CHO at 60 min after ingestion (p = .001). Plasma [K + ] a rose during and declined following each exercise bout in HIIC (p = .001), falling below baseline at 5 min post-exercise (p = .007). Both [K + ] a and [K + ] v were lower during CHO (p = .036, p = .001, respectively, treatment main effect). The [K + ] a-v diff across the forearm widened during exercise (p = .001), returned to baseline during recovery, and was greater in CHO than CON during EB1, EB2 (p = .001) and EB3 (p = .005). Time to fatigue did not differ between trials., Conclusion: Acute oral glucose ingestion, as used in a glucose tolerance test, induced a small, systemic K + -lowering effect before, during, and after HIIC, that was detectable in both arterial and venous plasma. This likely reflects insulin-mediated, increased Na + ,K + -ATPase induced K + uptake into non-contracting muscles. However, glucose ingestion did not delay fatigue., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Lifestyle is fundamental in chronic disease prevention and management, and it has been recommended as a first-line treatment in the Australian polycystic ovary syndrome (PCOS) guideline 2011. The first international evidence-based guideline on PCOS was developed in 2018, which expanded the scope and evidence in the Australian guideline. This paper summarizes the lifestyle recommendations and evidence summaries from the guideline. International multidisciplinary guideline development groups delivered the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2018. The process followed the Appraisal of Guidelines for Research and Evaluation II and The Grading of Recommendations, Assessment, Development and Evaluation framework. Extensive communication and meetings addressed six prioritized clinical questions through five reviews. Evidence-based recommendations were formulated before consensus voting within the panel. Evidence shows the benefits of multicomponent lifestyle intervention, efficacy of exercise and weight gain prevention with no specific diet recommended. Lifestyle management is the first-line management in the intervention hierarchy in PCOS. Multicomponent lifestyle intervention including diet, exercise and behavioural strategies is central to PCOS management with a focus on weight and healthy lifestyle behaviours. The translation programme optimizes reach and dissemination for health professionals and consumers., (© 2020 World Obesity Federation.)

Background: Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with reproductive and metabolic manifestations. Exercise training has consistently been found to result in improved clinical outcomes in women with PCOS, but shortfalls with exercise prescription are evident. The aim of this systematic review and meta-analysis was to identify exercise intervention characteristics that provide favourable outcomes in women with PCOS. Methods: A systematic review of published literature was conducted using EBSCOhost and Ovid Medline up to May 2019. The review adheres to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines as per our PROSPERO protocol (CRD42018088367). Randomised controlled trials, non-randomised controlled trials, and uncontrolled trials that evaluated an exercise intervention of at least moderate intensity in women with PCOS were included. Meta-analyses were performed using general linear mixed modelling and Bayesian inferences about effect magnitudes. Results: Thirty-three articles were identified for systematic review of which 19 were meta-analysed. Intervention duration ranged from 6 to 26 weeks. A total number of 777 women were included in the meta-analysis. The meta-analysis found that improvements in health outcomes are more dependent on exercise intensity rather than dose. Fixed effects analysis reported a moderate increase in VO 2peak (24.2%; 90% CL, 18.5-30.1), and small reductions in HOMA-IR (-36.2%; 90% CL, -55.3 to -9.0), and waist circumference (-4.2%; 90% CL -6.0 to -2.3) as a result of vigorous intensity exercise. These results are confirmed in the predicted analysis which reported the greatest improvements in VO 2peak , BMI, and waist circumference after vigorous intensity exercise alone or when combined with diet, particularly for women with clinically adverse baseline values. Conclusions: Exercise training in the management of PCOS is becoming more common. Results from our analysis support the use of exercise and suggest that vigorous intensity exercise may have the greatest impact on cardiorespiratory fitness, body composition, and insulin resistance. Our results indicate that, a minimum of 120 min of vigorous intensity per week is needed to provide favourable health outcomes for women with PCOS with studies of longer duration required to evaluate outcomes with sustained exercise., (Copyright © 2020 Patten, Boyle, Moholdt, Kiel, Hopkins, Harrison and Stepto.)

Pattison, KJ, Drinkwater, EJ, Bishop, DJ, Stepto, NK, and Fyfe, JJ. Modulation of countermovement jump-derived markers of neuromuscular function with concurrent vs. single-mode resistance training. J Strength Cond Res 34(6): 1497-1502, 2020-This study assessed changes in countermovement jump (CMJ)-derived markers of neuromuscular function with concurrent training vs. resistance training (RT) alone and determined associations between changes in CMJ parameters and other neuromuscular adaptations (e.g., maximal strength gain). Twenty-three recreationally active men performed 8 weeks of RT alone (RT group, n = 8) or combined with either high-intensity interval training cycling (HIIT + RT group, n = 8) or moderate-intensity continuous cycling (MICT + RT group, n = 7). Maximal strength and CMJ performance were assessed before (PRE), after 4 weeks of training (MID), and >72 hours (maximal strength) or >5-7 days (CMJ performance) after (POST) the training intervention. Improvements in CMJ relative peak force from both PRE to MID and PRE to POST were attenuated for both HIIT + RT (effect size [ES]: -0.44; ±90% confidence limit, ±0.51 and ES: -0.72; ±0.61, respectively) and MICT + RT (ES: -0.74; ±0.49 and ES: -1.25; ±0.63, respectively). Compared with RT alone, the change in the flight time to contraction time ratio (FT:CT) was attenuated from PRE to MID for MICT + RT (ES: -0.38; ±0.42) and from PRE to POST for both MICT + RT (ES: -0.60; ±0.55) and HIIT + RT (ES: -0.75; ±0.30). PRE to POST changes in both CMJ relative peak force and flight time:contraction time (F:C) ratio were also associated with relative 1 repetition maximum leg press strength gain (r = 0.26 and 0.19, respectively). These findings highlight the utility of CMJ testing for monitoring interference to improvements in neuromuscular function with concurrent training.

Aims: This scoping review determines the breadth and outcomes of controlled trials testing the effect of physical activity/exercise interventions across mental health outcomes in young people with a mental disorder., Methods: The literature search was conducted using the open-access 'Evidence Finder', a comprehensive youth mental health-specific database that is systematically populated from MEDLINE, Embase, PsycINFO and Cochrane CENTRAL databases., Results: Sixteen publications were identified after meeting the following eligibility criteria: (1) participants were young people (mean age 12-25.9 years) with a mental disorder diagnosed by a trained clinician or by reaching a predefined cut score on a symptom measure, (2) interventions were exercise, (3) designs were randomised or non-randomised controlled trials, (4) outcomes were mental health related. Eight studies included young people with depression, three included people with psychosis/schizophrenia, three included people with eating disorders and two included people with anxiety. The available evidence suggests that moderate-to-vigorous-intensity exercise may be beneficial, particularly for reducing depression. The available evidence for other intervention intensities, and for other mental disorders, is mixed., Conclusions: Overall, the evidence regarding the impact of exercise interventions on a range of mental health outcomes in clinical populations of young people with various mental disorders looks promising but requires further development. Findings from this scoping review can inform the development of future exercise interventions in the youth mental health field., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways., Methods: A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training., Results: We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3., Conclusions: We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.

Context: Polycystic ovary syndrome (PCOS) is a chronic disease affecting reproductive function and whole-body metabolism. Although the etiology is unclear, emerging evidence indicates that the epigenetics may be a contributing factor., Objective: To determine the role of global and genome-wide epigenetic modifications in specific immune cells in PCOS compared with controls and whether these could be related to clinical features of PCOS., Design: Cross-sectional study., Participants: Women with (n = 17) or without PCOS (n = 17)., Setting: Recruited from the general community., Main Outcome Measures: Isolated peripheral blood mononuclear cells were analyzed using multicolor flow cytometry methods to determine global DNA methylation levels in a cell-specific fashion. Transcriptomic and genome-wide DNA methylation analyses were performed on T helper cells using RNA sequencing and reduced representation bisulfite sequencing., Results: Women with PCOS had lower global DNA methylation in monocytes (P = 0.006) and in T helper (P = 0.004), T cytotoxic (P = 0.004), and B cells (P = 0.03). Specific genome-wide DNA methylation analysis of T helper cells from women with PCOS identified 5581 differentially methylated CpG sites. Functional gene ontology enrichment analysis showed that genes located at the proximity of differentially methylated CpG sites belong to pathways related to reproductive function and immune cell function. However, these genes were not altered at the transcriptomic level., Conclusions: It was shown that PCOS is associated with global and gene-specific DNA methylation remodeling in a cell type-specific manner. Further investigation is warranted to determine whether epigenetic reprogramming of immune cells is important in determining the different phenotypes of PCOS., (Copyright © 2019 Endocrine Society.)

Context: Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle., Current Knowledge: PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle., Future Directions: Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies., Conclusion: Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions., (Copyright © 2019 Endocrine Society.)

Polycystic Ovary Syndrome (PCOS) is a complex condition with mechanisms likely to involve the interaction between genetics and lifestyle. Familial clustering of PCOS symptoms is well documented, providing evidence for a genetic contribution to the condition. This overview aims firstly to systematically summarise the current literature surrounding genetics and PCOS, and secondly, to assess the methodological quality of current systematic reviews and identify limitations. Four databases were searched to identify candidate gene systematic reviews, and quality was assessed with the AMSTAR tool. Genome-wide association studies (GWAS) were identified by a semi structured literature search. Of the candidate gene systematic reviews, 17 were of high to moderate quality and four were of low quality. A total of 19 gene loci have been associated with risk of PCOS in GWAS, and 11 of these have been replicated across two different ancestries. Gene loci were located in the neuroendocrine, metabolic, and reproductive pathways. Overall, the gene loci with the most robust findings were THADA, FSHR, INS-VNTR , and DENND1A , that now require validation. This overview also identified limitations of the current literature and important methodological considerations for future genetic studies. Much work remains to identify causal variants and functional relevance of genes associated with PCOS., Competing Interests: Laven reports grants from Ferring BV, grants from PregLem/Gedeon Richter, personal fees from Danone, personal fees from Roche during the conduct of the study. Hiam, D., Moreno-Asso, A., Teede, H., Stepto, N.K., Moran, L.J., Gibson-Helm, M. declare no potential conflict of interest.

In this opinion piece, we summarize, discuss implications of implementation, and critically evaluate our 2018 evidence-based guideline recommendations for exercise and physical activity in women with polycystic ovary syndrome (PCOS). We developed recommendations as part of a larger international guideline development project. The overall guideline scope and priorities were informed by extensive health professional and consumer engagement. The lifestyle guideline development group responsible for the exercise recommendations included experts in endocrinology, exercise physiology, gynecology, dietetics, and obstetrics, alongside consumers. Extensive online communications and two face-to-face meetings addressed five prioritized clinical questions related to lifestyle, including the role of exercise as therapy for women with PCOS. The guideline recommendations were formulated based on one narrative and two evidence-based reviews, before consensus voting within the guideline panel. The development process was in accordance with the Appraisal of Guidelines for Research and Evaluation (AGREE) II, and used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework to assess evidence quality, desirable and undesirable consequences, feasibility, acceptability, cost, implementation, and recommendation strength. Given the evidence for exercise as therapy in PCOS being of low quality, a consensus recommendation was made based on current exercise guidelines for the general population. Women with PCOS and clinicians are forced to adopt generic approaches when recommending exercise therapy that perpetuates clinical management with pharmacological solutions. The current status of evidence highlights the need for greater international co-operation between researchers and funding agencies to address key clinical knowledge gaps around exercise therapy in PCOS to generate evidence for appropriate, scalable, and sustainable best practice approaches.

Polycystic ovary syndrome (PCOS) is a complex condition that involves metabolic, psychological and reproductive complications. Insulin resistance underlies much of the pathophysiology and symptomatology of the condition and contributes to long term complications including cardiovascular disease and diabetes. Women with PCOS are at increased risk of obesity which further compounds metabolic, reproductive and psychological risks. Lifestyle interventions including diet, exercise and behavioural management have been shown to improve PCOS presentations across the reproductive, metabolic and psychological spectrum and are recommended as first line treatment for any presentation of PCOS in women with excess weight by the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2018. However, there is a paucity of research on the implementation lifestyle management in women with PCOS by healthcare providers. Limited existing evidence indicates lifestyle management is not consistently provided and not meeting the needs of the patients. In this review, barriers and facilitators to the implementation of evidence-based lifestyle management in reference to PCOS are discussed in the context of a federally-funded health system. This review highlights the need for targeted research on the knowledge and practice of PCOS healthcare providers to best inform implementation strategies for the translation of the PCOS guidelines on lifestyle management in PCOS., Competing Interests: The authors declare no conflict of interest.

Background: Clinical risk prediction tools for gestational diabetes (GDM) may be enhanced by measuring biomarkers in early pregnancy., Aim: To evaluate a two-step GDM risk prediction tool incorporating fasting glucose (FG) and serum biomarkers in early pregnancy., Materials and Methods: High molecular weight (HMW) adiponectin, omentin-1 and interleukin-6 (IL-6) were measured at 12-15 weeks gestation in women with high risk of GDM from a randomised trial using a clinical risk prediction tool. GDM diagnosis (24-28 weeks) was evaluated using 1998 Australian Diabetes in Pregnancy (ADIPS) criteria and newer International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Associations between biomarkers and development of GDM were examined using multivariable regression analysis. Area under the receiver-operator curve (AUC), sensitivity and specificity were calculated to determine classification ability of each model compared to FG and maternal characteristics., Results: HMW adiponectin improved prediction of ADIPS GDM (AUC 0.85, sensitivity 50%, specificity 96.2%, P = 0.04), compared to FG and maternal factors (0.78, 35% and, 98.1%, respectively). HMW adiponectin <1.53 μg/mL further improved the model (AUC 0.87, sensitivity 75%, specificity 88.2%, P = 0.01). HMW adiponectin did not improve prediction of IADPSG GDM (AUC 0.84, sensitivity 64%, specificity 97.9%, P = 0.22) compared to FG and maternal factors (0.79, 56%, 93.8%). Omentin-1 and IL-6 did not significantly improve classification ability for GDM., Conclusions: A two-step approach combining FG and HMW adiponectin to a validated clinical risk prediction tool improved sensitivity and predictive ability for ADIPS GDM. Further research is required to enhance GDM prediction using IADPSG criteria for application in clinical practice., (© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: Many complex diseases exhibit co-morbidities often requiring management by more than one health specialist. We examined cross-speciality issues that ultimately affect the health and wellbeing of patients with polycystic ovary syndrome (PCOS). PCOS was originally described as a reproductive condition but is now recognised to also be a metabolic and psychological condition affecting 8-13% of women of reproductive age. With a four-fold increased risk of type 2 diabetes (DM2), the Population Attributable Risk of DM2 that could be avoided if PCOS were eliminated is a substantial 19-28% of women of reproductive age. To determine the extent to which PCOS is an important consideration in diabetes development, we examined publications, funding, guidelines and predictors of risk of developing DM2., Results: We found that the topic of PCOS appeared in specialist diabetes journals at only 10% the rate seen in endocrinology journals - about 1 in 500 articles. We found research funding to be substantially less than for diabetes and found that diabetes guidelines and predictive tools for DM2 risk mostly ignore PCOS. This is surprising since insulin resistance in women with PCOS has a different aetiology and additionally women with PCOS are at increased risk of becoming overweight or obese - high risk factors for DM2., Conclusions: We consider the causes of these concerning anomalies and discuss current activities to address the co-morbidities of PCOS, including the recent development of international guidelines, an international PCOS awareness program and potentially changing the name of PCOS to better reflect its metabolic consequences.

Bone remodeling markers (BRMs) are suppressed following the consumption of a meal. Our findings indicate that a single session of continuous moderate-intensity exercise, but not low-volume high-intensity interval exercise, performed 1 h after a meal attenuates the postprandial suppression of BRMs., Introduction: Acute exercise transiently increases BRMs including osteocalcin (tOC) and the undercarboxylated form of osteocalcin (ucOC), a hormone that is implicated in glucose regulation. The effects of acute exercise and exercise-intensity on postprandial levels of tOC and ucOC are unknown., Methods: Twenty-seven adults that were overweight or obese (age 30 ± 1 years; BMI 30 ± 1 kg∙m -2 ; mean ± SEM) were randomly allocated to perform a single session of low-volume high-intensity interval exercise (LV-HIIE; nine females, five males) or continuous moderate-intensity exercise (CMIE; eightfemales, five males) 1 h after consumption of a standard breakfast. Serum tOC, ucOC, and ucOC/tOC were measured at baseline, 1 h, and 3 h after breakfast consumption on a rest day (no exercise) and the exercise day (exercise 1 h after breakfast)., Results: Compared to baseline, serum tOC and ucOC were suppressed 3 h after breakfast on the rest day (- 10 ± 1% and - 6 ± 2%, respectively; p < 0.05), whereas ucOC/tOC was elevated (2.5 ± 1%; p = 0.08). Compared to the rest day, CMIE attenuated the postprandial-induced suppression of tOC (rest day - 10 ± 2% versus CMIE - 5 ± 2%, p < 0.05) and ucOC (rest day - 6 ± 4% versus CMIE 11 ± 2%, p < 0.05), and increased postprandial ucOC/tOC (rest day 3 ± 2% versus CMIE 15 ± 1%, p < 0.05). In contrast, LV-HIIE did not alter postprandial tOC, ucOC, or ucOC/tOC (all p > 0.1)., Conclusions: Acute CMIE, but not LV-HIIE, attenuates the postprandial-induced suppression of tOC and ucOC. CMIE may be an effective tool to control the circulating levels of BRMs following meal consumption in overweight/obese adults.