Bone health in women with premature ovarian insufficiency/early menopause: a 23-year longitudinal analysis.

STUDY QUESTION: What is the frequency of, and predictors for, osteoporosis, fractures, and osteoporosis management (investigation, treatment) in women with premature ovarian insufficiency (POI; menopause <40 years) and early menopause (EM; menopause 40-44years)? SUMMARY ANSWER: Over the 23-year follow-up duration, at a mean age of 68 years, women with POI/EM had higher osteoporosis/fracture risk and prevalence, higher osteoporosis screening and anti-osteoporosis medication use compared to women with usual age menopause; increasing age was predictive of increased risk of osteoporosis/fracture and menopause hormone therapy (MHT) prior to or at study entry (aged 45-50 years) was protective. WHAT IS KNOWN ALREADY: Women with POI/EM have increased risk of osteoporosis and fractures with limited data regarding risk factors for reduced bone density and fractures. Clinical guidelines recommend screening with dual X-ray absorptiometry (DXA) and treatment with MHT for most women with POI/EM to reduce osteoporosis and fracture risk; however, studies indicate gaps in osteoporosis knowledge, guideline uptake, and management adherence by clinicians and women. STUDY DESIGN, SIZE, DURATION: The Australian Longitudinal Study on Women's Health is a prospective longitudinal study of Australian women. This study uses the cohort of women born between 1946 and 1951, surveyed nine times between 1996 and 2019. Data from the Australian administrative health records, including hospital admissions data (fractures, osteoporosis), Medicare Benefits Schedule (DXA), and the Pharmaceutical Benefits Scheme (PBS; MHT, anti-osteoporosis medication, available only from 2002) were linked to survey data. PARTICIPANTS/MATERIALS, SETTING, METHODS: Survey respondents with self-reported age of menopause were included. POI/EM was defined as menopause <45 years. T-test or chi-square were used for comparisons at baseline (P < 0.05 indicates significance). Generalized estimating equations for panel data explored predictors for the longitudinal outcomes of osteoporosis, fractures, DXA rates, MHT use, and anti-osteoporosis medication (in women with osteoporosis/fracture, from Survey 4 onwards only). Univariable regression was performed, and variables retained where P < 0.2, to form the multivariable model, and bootstrapping with 100 repetitions at 95% sampling of the original dataset to ensure robustness of results. MAIN RESULTS AND THE ROLE OF CHANCE: Eight thousand six hundred and three women were included: 610 (7.1%) with POI/EM. Mean (SD) baseline age was 47.6 (1.45) years in the entire cohort and mean (SD) age of menopause was 38.2 (7.95) and 51.3 (3.04) years in women with POI/EM and usual age menopause, respectively (P < 0.001). Over the 23 years, of women with POI/EM, 303 (49.7%) had osteoporosis/fractures, 421 (69.0%) had DXA screening, 474 ever used MHT (77.7%), and 116 (39.1%) of those with osteoporosis/fractures used anti-osteoporosis medication. Of women with usual age menopause, 2929 (36.6%) had osteoporosis/fractures, 4920 (61.6%) had DXA screening, 4014 (50.2%) used MHT, and 964 (33.0%) of those with osteoporosis/fractures used anti-osteoporosis medication. Compared to women with menopause at age ≥45 years and after adjusting for other risk factors, women with POI/EM had increased risk of osteoporosis (odds ratio [OR] 1.37; 95% CI 1.07-1.77), fractures (OR 1.45; 1.15-1.81), DXA testing (OR 1.64; 1.42-1.90), MHT use (OR 6.87; 5.68-8.30), and anti-osteoporosis medication use (OR 1.50; 1.14-1.98). In women with POI/EM women, increasing age was associated with greater risk of osteoporosis/fracture (OR 1.09; 1.08-1.11), and MHT prior to or at study entry (aged 45-50 years), was protective (OR 0.65, 0.45-0.96). In women with POI/EM, age (OR 1.11; 1.10-1.12), fractures (OR 1.80, 1.38-2.34), current smoking (OR 0.60; 0.43-0.86), and inner (OR 0.68; 0.53-0.88) or outer regional (OR 0.63; 0.46-0.87) residential location were associated with DXA screening. In women with POI/EM, increasing age (OR 1.02; 1.01-1.02), and currently consuming alcohol (OR 1.17; 1.06-1.28), was associated with having ever used MHT. In the 299 women with POI/EM and osteoporosis/fractures, only 39.1% ever received treatment with an anti-osteoporosis medication. Increasing age (OR 1.07; 1.04-1.09) and lower BMI (OR 0.95; 0.92-0.98) were associated with greater likelihood of treatment with anti-osteoporosis medication. LIMITATIONS, REASONS FOR CAUTION: Survey data including age of menopause were self-reported by participants; fracture questions were not included in the 2001 survey, and location or level of trauma of self-reported fractures was not asked. Additional risk/protective factors such as vitamin D status, calcium intake, and exercise were not able to be included. Due to sample size, POI and EM were combined for all analyses, and we were unable to differentiate between causes of POI/EM. PBS data were only available from 2004, and hospital admissions data were state-based, with all of Australia were only available from 2007. WIDER IMPLICATIONS OF THE FINDINGS: This study supports previous literature indicating increased risk of osteoporosis and fractures in women with POI, and adds evidence for women with POI/EM, where there was a relative paucity of data. This is the first study to analyse a variety of clinical and demographic risk factors for osteoporosis and fractures in women with POI/EM, as well as analysing investigation and treatment rates. In these women, using MHT prior to or at study entry, aged 45-50 years, was protective for osteoporosis/fractures; however, having ever used MHT was not, highlighting the importance of early treatment with MHT in these women to preserve bone strength. Although women with POI/EM and osteoporosis or fractures were more likely to use anti-osteoporosis medications than those with usual age menopause, overall treatment rates are low at <40%, demonstrating a significant treatment gap that should be addressed to reduce future fracture risk. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Australian NHMRC Centre of Research Excellence Women's Health in Reproductive Life (CRE-WHIRL, project number APP1171592). A.R.J. is the recipient of a National Health and Medical Research Council post-graduate research scholarship (grant number 1169192). P.R.E. is supported by a National Health and Medical Research Council grant 1197958. P.R.E. reports grants paid to their institution from Amgen, Sanofi, and Alexion, honoraria from Amgen paid to their institution, and honoraria from Alexion and Kyowa-Kirin. TRIAL REGISTRATION NUMBER: N/A.

Learning health systems and evidence ecosystems: a perspective on the future of evidence-based medicine and evidence-based guideline development.

Despite forming the cornerstone of modern clinical practice for decades, implementation of evidence-based medicine at scale remains a crucial challenge for health systems. As a result, there has been a growing need for conceptual models to better contextualise and pragmatize the use of evidence-based medicine, particularly in tandem with patient-centred care. In this commentary, we highlight the emergence of the learning health system as one such model and analyse its potential role in pragmatizing both evidence-based medicine and patient-centred care. We apply the learning health system lens to contextualise the key activity of evidence-based guideline development and implementation, and highlight how current inefficiencies and bottlenecks in the evidence synthesis phase of evidence-based guideline development threaten downstream adherence. Lastly, we introduce the evidence ecosystem as a complementary model to learning health systems, and propose how innovative developments from the evidence ecosystem may be integrated with learning health systems to better enable health impact at speed and scale.

Polycystic ovary syndrome: associations with cardiovascular disease.

Polycystic ovary syndrome (PCOS), characterized by abnormal menstrual periods, elevated androgen levels and polycystic ovary morphology on ultrasound, is the most common endocrine disorder among females. PCOS is associated with cardiovascular disease (CVD) risk factors including diabetes, obesity, metabolic syndrome, adverse pregnancy outcomes such as pre-eclampsia and psychosocial distress including depression. Previous evidence on the association between PCOS and CVD is inconclusive but the latest 2023 International Evidence-Based PCOS Guideline identifies PCOS as a risk factor for CVD. This review will discuss the relationship between PCOS and CVD along with current direction for CVD screening and prevention among individuals with PCOS.

Externally validated prediction models for pre-eclampsia: systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the performance of existing externally validated prediction models for pre-eclampsia (specifically for any- early- late-onset and preterm pre-eclampsia). METHODS: A systematic search was conducted in five databases (MEDLINE, Embase, Emcare, CINAHL, and Maternity and Infant Care Database) to identify studies based on Population, Index model, Comparator, Outcome, Timing, and Setting (PICOTS) approach until May 20, 2023. We extracted data using the CHARMS checklist and appraised risk of bias using PROBAST tool. Discrimination and calibration performance were meta-analysed when appropriate. RESULTS: Twenty-three publications reported 52 externally validated prediction models on pre-eclampsia (twenty any-onset, seventeen early-onset, fourteen late-onset, and one preterm pre-eclampsia). No model had the same set of predictors. Fifteen, two, and three any-onset pre-eclampsia models were externally validated once, twice, and thrice, respectively, and the Fetal Medicine Foundation (FMF) preterm model was widely validated in sixteen different settings. The most common predictors were maternal characteristics (pre-pregnancy BMI, prior pre-eclampsia, family history of pre-eclampsia, chronic medical conditions, and ethnicity) and biomarkers (uterine artery pulsatility index and pregnancy-associated plasma protein-A). The model for preterm pre-eclampsia (triple test FMF) had the best performances with a pooled area under the receiver operating characteristics curve (AUROC) of 0.90 (95% prediction interval (PI) 0.76 - 0.96) and was well-calibrated. The other models generally had poor to fair discrimination performance (AUROC median 0.66, range 0.53 to 0.77) and were overfitted in calibration after external validation. Apart from the FMF model, only the two most validated models in any-onset pre-eclampsia using isolated maternal characteristics, produced reasonable pooled AUROCs of 0.71 (95% PI 0.66 - 0.76) and 0.73 (0.55 - 0.86). CONCLUSION: Existing externally validated prediction models for any-, early-, and late-onset pre-eclampsia have limited discrimination and calibration performance with inconsistent input variables. The triple test FMF model had excellent discrimination performance in predicting preterm pre-eclampsia in numerous settings, but the inclusion of specialised biomarkers may limit feasibility and implementation outside of high-resource settings. This article is protected by copyright. All rights reserved.

Development, women-centricity and psychometric properties of maternity patient-reported outcome measures (PROMs): A systematic review.

BACKGROUND: Measuring maternity care outcomes based on what women value is critical to promoting woman-centred maternity care. Patient-reported outcome measures (PROMs) are instruments that enable service users to assess healthcare service and system performance. AIM: To identify and critically appraise the risk of bias, woman-centricity (content validity) and psychometric properties of maternity PROMs published in the scientific literature. METHODS: MEDLINE, CINAHL Plus, PsycINFO and Embase were systematically searched for relevant records between 01/01/2010 and 07/10/2021. Included articles underwent risk of bias, content validity and psychometric properties assessments in line with COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidance. PROM results were summarised according to language subgroups and an overall recommendation for use was determined. FINDINGS: Forty-four studies reported on the development and psychometric evaluation of 9 maternity PROMs, grouped into 32 language subgroups. Risk of bias assessments for the PROM development and content validity showed inadequate or doubtful methodological quality. Internal consistency reliability, hypothesis testing (for construct validity), structural validity and test-retest reliability varied markedly in sufficiency and evidence quality. No PROMs received a level 'A' recommendation, required for real-world use. CONCLUSION: Maternity PROMs identified in this systematic review had poor quality evidence for their measurement properties and lacked sufficient content validity, indicating a lack of woman-centricity in instrument development. Future research should prioritise women's voices in deciding what is relevant, comprehensive and comprehensible to measure, as this will impact overall validity and reliability and facilitate real-world use.

Levels of physical activity and sitting time in women with infants, toddlers and preschoolers: a population-based cross-sectional study.

OBJECTIVES: Insufficient physical activity (PA) and prolonged sitting time (ST) increase the risk of chronic disease and mortality. Caring for young children can potentially impact maternal PA and sedentary behaviours. The aims of this study were to explore the levels of PA and ST in women with young children (infants, toddlers and preschoolers) and sociodemographic and behavioural factors associated with these. STUDY DESIGN: This was a population-based cross-sectional study. METHODS: Survey 5 data collected in 2009 (n = 4290) of the 1973-1978 birth cohort of the Australian Longitudinal Study on Women's Health were used. Multiple linear and logistic regression models were used to examine associations. RESULTS: In adjusted models, compared with women with preschoolers, women whose youngest child was an infant aged 0-6 months, aged >6-12 months or toddler had lower PA (-321.3 MET.min/week [95% confidence interval (CI) -416.2, -226.4], -147.9 MET.min/week [95% CI -237.6, -58.1] and -106.4 MET.min/week [95% CI -172.3, -40.5]). ST was higher in women whose youngest child was an infant aged 0-6 months (0.48 h/day; 95% CI 0.19, 0.77) but lower with infants aged >6-12 months (-0.33 h/day; 95% CI -0.60, -0.05) and toddlers (-0.40 h/day; 95% CI -0.60, -0.20) than in those with preschoolers. The findings were similar in the logistic model. Sociodemographic and behavioural factors such as occupation and marital status also influenced PA and ST. CONCLUSIONS: Women with infants and toddlers have lower PA than women with preschoolers. Women are more likely to sit more in the first 6 months after childbirth. These findings can inform resources and intervention development to improve activity levels in women with young children through consideration of the age of the youngest child, sociodemographic and behavioural factors.

Increased mortality and non-cancer morbidity risk may be associated with early menopause and varies with aetiology: An exploratory population-based study using data-linkage.

OBJECTIVE: Iatrogenic early menopause (EM), that is, menopause before the age of 45 years due to surgery or chemotherapy or radiotherapy, is associated with negative health impacts. However, it is unclear how these vary according to the cause of EM. We investigated mortality and non-cancer morbidity in women with iatrogenic EM of different aetiologies. STUDY DESIGN: Population-based retrospective cohort study with 36-year follow-up using data-linkage with the Western Australia hospital morbidity database, cancer, birth and death registries, the midwives notification system and the mental health information system. The sample comprised women aged 20-44 years at index date with iatrogenic EM associated with breast or gynaecological cancer (n = 607), or benign bilateral oophorectomy (n = 414), and age-matched female controls (n = 16,998). Index date (breast, ovarian or uterine cancer diagnosis or oophorectomy procedure) ranged from 1982 to 1997, with follow-up until 2018. MAIN OUTCOME MEASURES: Mortality and hospitalisation for circulatory disorders, endocrine, psychological, respiratory, musculoskeletal and gastrointestinal morbidities. RESULTS: Significant differences in mortality were observed (% dead by follow-up: cancer, 53.0; oophorectomy, 10.9; and controls, 3.5; p < 0.001). Incidence rate ratios (IRRs) were increased for circulatory (1.23, 95 % CI 1.07-1.42) and endocrine disorders (1.31, 95%CI 1.08-1.56) and hip fracture (3.90, 95 % CI 1.83-7.40) in cancer survivors, compared with controls. IRRs for circulatory (0.62, 95 % CI 0.53-0.72) and endocrine disorders (0.62, 95 % CI 0.38-0.97) were reduced in the oophorectomy group, but were increased for psychological (8.53, 95 % CI 7.29-9.94) and gastrointestinal morbidities (1.43, 95%CI 1.21-1.67) compared with controls. CONCLUSION: Cancer-related or benign iatrogenic EM may be associated with increased mortality and morbidity, which vary with the cause of EM.

The diabetes-fracture association in women with type 1 and type 2 diabetes is partially mediated by falls: a 15-year longitudinal study.

This study evaluated mediators of fracture risk in postmenopausal women with type 1 (T1D) and type 2 diabetes (T2D), over a 15-year follow-up period. This study provides evidence that the increased fracture risk in women with T1D or T2D is partially explained by falls. Furthermore, a shorter reproductive lifespan in women with T1D contributes modestly to fracture risk in this cohort. PURPOSE: Skeletal fragility is associated with diabetes mellitus, while limited estrogen exposure during the reproductive years also predisposes to lower bone mass and higher fracture risk. We aimed to determine osteoporosis diagnosis, fall and fracture rates in women with type 1 (T1D) and type 2 (T2D) diabetes mellitus, and explore mediators of the diabetes-fracture relationship. METHODS: Prospective observational data drawn from the Australian Longitudinal Study in Women's Health (ALSWH) from 1996 to 2010. Women were randomly selected from the national health insurance database. Standardized data collection occurred at six survey time points, with main outcome measures being self-reported osteoporosis, incident fracture, falls, and reproductive lifespan. Mediation analyses were performed to elucidate relevant intermediaries in the diabetes-fracture relationship. RESULTS: Exactly 11,313 women were included at baseline (T1D, n = 107; T2D, n = 333; controls, n = 10,873). A total of 885 new cases of osteoporosis and 1099 incident fractures were reported over 15 years. Women with T1D or T2D reported more falls and fall-related injuries; additionally, women with T1D had a shorter reproductive lifespan. While fracture risk was increased in women with diabetes (T1D: OR 2.28, 95% CI 1.53-3.40; T2D: OR 2.40, 95% CI 1.90-3.03), compared with controls, adjustment for falls attenuated the risk of fracture by 10% and 6% in T1D and T2D, respectively. In women with T1D, reproductive lifespan modestly attenuated fracture risk by 4%. CONCLUSION: Women with T1D and T2D have an increased risk of fracture, which may be partially explained by increased falls, and to a lesser extent by shorter reproductive lifespan, in T1D.

Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis.

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 ß (TGFß)-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 TGFß 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 TGFß 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.

Women's perspectives of early menopause: development of a word cloud.

Objective: Early menopause (EM), menopause aged <45 years, occurs spontaneously or secondary to medical treatments and is associated with multiple health impacts. A word cloud is an image where the word size reflects the frequency of use. We aimed to assess the perspectives of women with EM using a word cloud.Methods: Women diagnosed with EM, recruited from clinics/community, completed a survey including the open-ended question 'What words do you associate with EM?'. Demographics and medical history were collected. Data analysis included descriptive statistics, identification of word themes/stems/synonyms, word frequency, and chi-square test. A word cloud was constructed from words used by two or more women using 'Wordle' (www.wordle.net).Results: Responses were obtained from 190/263 participants. The mean age was 54 ± 11 years, with EM diagnosed at age 38 ± 5 years. The cause of EM was unknown (30% of women), bilateral oophorectomy (27%), cancer therapy (25%), or autoimmune/genetic/metabolic (17%). The commonest words reported were hot flushes (36.8% of women), mood swings (20.5%), and infertility (16.8%), which varied with age and cause of EM. Few women reported neutral/positive words.Conclusion: Most words that women associate with EM have negative connotations and refer to symptoms. A word cloud is a novel way to illustrate women's perspectives.

Evidence summaries and recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome: assessment and treatment of infertility.

STUDY QUESTION: What is the recommended assessment and management of infertile women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertize and consumer preference? SUMMARY ANSWER: International evidence-based guidelines, including 44 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of infertile women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines on PCOS lacked rigorous evidence-based processes, failed to engage consumer and multidisciplinary perspectives or were outdated. The assessment and management of infertile women with PCOS are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. PARTICIPANTS/MATERIALS SETTING METHODS: Governance included a six continent international advisory and a project board, a multidisciplinary international guideline development group (GDG), consumer and translation committees. Extensive health professional and consumer engagement informed the guideline scope and priorities. The engaged international society-nominated panel included endocrinology, gynaecology, reproductive endocrinology, obstetrics, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Extensive online communication and two face-to-face meetings over 15 months addressed 19 prioritized clinical questions involving nine evidence-based reviews and 10 narrative reviews. Evidence-based recommendations (EBRs) were formulated prior to consensus voting within the guideline panel. STUDY DESIGN SIZE DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. A (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, desirable and undesirable consequences, feasibility, acceptability, cost, implementation and ultimately recommendation strength. The guideline was peer-reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREE II criteria and underwent methodological review. This guideline was approved by all members of the GDG and has been approved by the NHMRC. MAIN RESULTS AND THE ROLE OF CHANCE: The quality of evidence (QOE) for the EBRs in the assessment and management of infertility in PCOS included very low (n = 1), low (n = 9) and moderate (n = 4) quality with no EBRs based on high-quality evidence. The guideline provides 14 EBRs, 10 clinical consensus recommendations (CCRs) and 20 clinical practice points on the assessment and management of infertility in PCOS. Key changes in this guideline include emphasizing evidence-based fertility therapy, including cheaper and safer fertility management. LIMITATIONS REASONS FOR CAUTION: Overall evidence is generally of low to moderate quality, requiring significantly greater research in this neglected, yet common condition. Regional health systems vary and a process for adaptation of this guideline is provided. WIDER IMPLICATIONS OF THE FINDINGS: The international guideline for the assessment and management of infertility in PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTERESTS: The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine (ASRM). GDG members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Norman has declared a minor shareholder interest in the IVF unit Fertility SA, travel support from Merck and grants from Ferring. Prof. Norman also has scientific advisory board duties for Ferring. The remaining authors have no conflicts of interest to declare.This article was not externally peer-reviewed by Human Reproduction Open.

Impact of different glycaemic treatment targets on pregnancy outcomes in gestational diabetes.

AIM: With no current randomized trials, we explored the impact of tight compared with standard treatment targets on pregnancy outcomes in gestational diabetes mellitus (GDM). METHODS: This cohort study of singleton births ≥ 28 weeks' gestation was conducted at two major Australian maternity services (2009-2013). Standardized maternal, neonatal and birth outcomes were examined using routine healthcare data and compared for women with GDM at Service One (n = 2885) and Service Two (n = 1887). Services applied different treatment targets: Service One (standard targets, reference group) fasting < 5.5 mmol/l, 2-h postprandial < 7.0 mmol/l; Service Two (tight targets) fasting < 5.0 mmol/l, 2-h postprandial < 6.7 mmol/l. Multivariable regression with propensity score adjustment was used to examine associations between targets and outcomes. RESULTS: GDM prevalence and insulin use were 7.9% and 31% at Service One, and 5.7% and 46% at Service Two. There were no differences in primary outcomes: birthweight > 90th centile [adjusted odds ratio (OR) 1.06, 95% confidence interval (CI) 0.87-1.30] and < 10th centile (OR 0.84, 95% CI 0.70-1.01), or secondary outcomes gestational hypertension, pre-eclampsia, shoulder dystocia or a perinatal composite. Service Two with tight targets had increased induction of labour (OR 3.63, 95% CI 3.17-4.16), elective Caesarean section (OR 1.75, 95% CI 1.37-2.23) and Apgar scores < 7 at 5 min (OR 1.54, 95% CI 1.05-2.25), decreased hypoglycaemia (OR 0.76, 95% CI 0.61-0.94]), jaundice (OR 0.47, 95% CI 0.35-0.63) and respiratory distress (OR 0.68, 95% CI 0.47-0.98). CONCLUSIONS: Tight GDM treatment targets were associated with greater insulin use and no difference in primary birthweight outcomes. The service with tight targets had higher obstetric intervention, lower rates of reported hypoglycaemia, jaundice, respiratory distress and lower Apgar scores. High-quality interventional data are required before tight treatment targets can be implemented.

A lifestyle intervention programme for the prevention of Type 2 diabetes mellitus among South Asian women with gestational diabetes mellitus [LIVING study]: protocol for a randomized trial.

AIM: This study aims to determine whether a resource- and culturally appropriate lifestyle intervention programme in South Asian countries, provided to women with gestational diabetes (GDM) after childbirth, will reduce the incidence of worsening of glycaemic status in a manner that is affordable, acceptable and scalable. METHODS: Women with GDM (diagnosed by oral glucose tolerance test using the International Association of the Diabetes and Pregnancy Study Groups criteria) will be recruited from 16 hospitals in India, Sri Lanka and Bangladesh. Participants will undergo a repeat oral glucose tolerance test at 6 ± 3 months postpartum and those without Type 2 diabetes, a total sample size of 1414, will be randomly allocated to the intervention or usual care. The intervention will consist of four group sessions, 84 SMS or voice messages and review phone calls over the first year. Participants requiring intensification of the intervention will receive two additional individual sessions over the latter half of the first year. Median follow-up will be 2 years. The primary outcome is the proportion of women with a change in glycaemic category, using the American Diabetes Association criteria: (i) normal glucose tolerance to impaired fasting glucose, or impaired glucose tolerance, or Type 2 diabetes; or (ii) impaired fasting glucose or impaired glucose tolerance to Type 2 diabetes. Process evaluation will explore barriers and facilitators of implementation of the intervention in each local context, while trial-based and modelled economic evaluations will assess cost-effectiveness. DISCUSSION: The study will generate important new evidence about a potential strategy to address the long-term sequelae of GDM, a major and growing problem among women in South Asia. (Clinical Trials Registry of India No: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry No: SLCTR/2017/001; and ClinicalTrials.gov Identifier No: NCT03305939).

Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression.

INTRODUCTION: Women with polycystic ovary syndrome (PCOS) have increased risk of metabolic syndrome. The relative contribution of clinical, demographic or biochemical factors to metabolic syndrome in PCOS is not known. A literature search was conducted in MEDLINE, CINAHL, EMBASE and clinical trial registries. Of 4530 studies reviewed, 59 were included in the systematic review and 27 in the meta-analysis and meta-regression. In good and fair quality studies, women with PCOS had an overall increased prevalence of metabolic syndrome (odds ratio, OR 3.35, 95% confidence interval, CI 2.44, 4.59). Increased prevalence of metabolic syndrome occurred in overweight or obese women with PCOS (OR 1.88, 95% 1.16, 3.04) but not in lean women (OR 1.45, 95% CI 0.35, 6.12). In meta-regression analyses, the markers of metabolic syndrome diagnostic criteria (waist circumference, high-density lipoprotein cholesterol, triglyceride, blood pressure), BMI, glucose tolerance (2-hr oral glucose tolerance test) and surrogate markers of insulin resistance (HOMA-IR) but not markers of reproductive dysfunction (sex hormone binding globulin, testosterone, PCOS phenotypes) contributed significantly to the heterogeneity in the prevalence of metabolic syndrome. Women with PCOS have increased risk of metabolic syndrome which was associated with obesity and metabolic features but not with indices of hyperandrogenism.

Cardiometabolic risks in PCOS: a review of the current state of knowledge.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting up to 18% women of reproductive age. It is associated with a range of metabolic, reproductive, and psychological features. Current evidence indicates a role of PCOS in the development of metabolic and increased cardiovascular risk factors (CVRF) with implications for compromised cardiovascular endpoint disease, which may have a considerable impact on health and health care costs. AREAS COVERED: Existing studies examining long-term cardiometabolic health in PCOS are heterogeneous with inconsistent findings. In the current review, we aim to explore and critically review retrospective, prospective, meta-analysis and review articles relating to PCOS on cardiometabolic risk factors and clinical consequences to summarize the evidence, note evidence gaps, and suggest implications for future research. EXPERT COMMENTARY: Although there is an established association between PCOS and metabolic health, implications on cardiac health are more uncertain with associations observed for CVRF and subclinical disease, yet limited and conflicting data on actual cardiovascular endpoints. There is a lack of population-based long-term studies examining cardiometabolic morbidity and mortality in PCOS with a need for further research to progress toward a better understanding of the long-term cardiometabolic impacts in women with PCOS.

Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression.

BACKGROUND: Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity. OBJECTIVE AND RATIONALE: We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS. SEARCH METHODS: We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis. OUTCOMES: We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for diagnosing diabetes. The ethnicity-related difference retained its significance for Asia and Europe in BMI-matched subgroups. Clear contributors to heterogeneity did not emerge in meta-regression. WIDER IMPLICATIONS: Our findings underscore the importance of PCOS as a cause of dysglycemia with a higher prevalence of IGT and T2DM. They support the relevance of ethnicity and obesity and emphasize the need for accurate diagnostic methods for diabetes. PROSPERO REGISTRATION NUMBER: CRD42017056524.