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.

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.

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).

Performance of mass spectrometry steroid profiling for diagnosis of polycystic ovary syndrome.

STUDY QUESTION: How well does multi-analyte steroid mass spectrometry (MS) profiling classify women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Our liquid chromatography MS (LC-MS) steroid profiling only minimally improves discrimination of women with and without PCOS compared with a direct testosterone immunoassay (T_IA) and the free androgen index (FAI). WHAT IS KNOWN ALREADY: Blood testosterone measured by direct (non-extraction) immunoassay overlaps between women with and without PCOS. Multi-analyte MS provides greater specificity and accuracy for steroid measurement so might improve the classification. STUDY DESIGN, SIZE, DURATION: An observational, cross-sectional study of women with PCOS (n = 152) defined by Rotterdam criteria and matched non-PCOS (n = 45) control women was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum steroid profiles of testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione (A4), estradiol (E2), estrone (E1), 17 hydroxy progesterone (17OHP4), progesterone (P4) and cortisol were measured by LC-MS; T_IA and sex hormone binding globulin were measured by immunoassay; and FAI, calculated free testosterone (cFT) and total androgen index (TAI) were calculated. Classification was based on logistic regression with corresponding univariate and multivariate C-statistics. MAIN RESULTS AND THE ROLE OF CHANCE: Serum testosterone by immunoassay demonstrated levels more than 100% higher than that measured by LC-MS. Compared with the controls, women with PCOS had higher serum T, DHEA, A4, TAI, T_IA, cFT, FAI and E2 but not serum DHT, E1, P4, 17OHP4 or cortisol. Univariate C-statistics were highest for FAI (0.89) and T_IA (0.82) compared with other androgens (T [0.72], DHT [0.40]), pro-androgens (A4 [0.74], DHEA[0.71]) or derivatives (cFT [0.75], TAI [0.60]). For all multivariate models, the overall correct predictions (81-86%) featured high sensitivity (92-96%) but low specificity (28-43%). and substituting LC-MS steroid measurements for T_IA and FAI produced only minimal improvements in classification. LIMITATIONS REASONS FOR CAUTION: The study cohort is limited in size and only unconjugated steroids were measured. WIDER IMPLICATIONS OF THE FINDINGS: Multi-analyte steroid profiling of unconjugated circulating steroids provides only limited improvement on direct T_IA in classifying women with and without PCOS. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

Systematic review and meta-analysis of the impact of preconception lifestyle interventions on fertility, obstetric, fetal, anthropometric and metabolic outcomes in men and women.

STUDY QUESTION: What is the impact of preconception lifestyle interventions on live birth, birth weight and pregnancy rate? SUMMARY ANSWER: Lifestyle interventions showed benefits for weight loss and increased natural pregnancy rate, but not for live birth or birth weight. WHAT IS KNOWN ALREADY: Evidence on the practice and content of preconception counseling and interventions is variable and limited. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis (MA). Main search terms were those related to preconception lifestyle. Database searched were Ovid MEDLINE(R), EBM Reviews, PsycINFO, EMBASE and CINAHL Plus. No language restriction was placed on the published articles. The final search was performed on 10 January 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were non-pregnant women of childbearing age intent on conceiving or their male partners. Exclusion criteria include participants with BMI < 18 kg/m2, animal trials, hereditary disorder in one or both partners and trials focusing solely on alcohol or smoking cessation/reduction, micronutrient supplementation, or diabetes control. Anthropometric, fertility, obstetric and fetal outcomes were assessed. Bias and quality assessments were performed. MAIN RESULTS AND THE ROLE OF CHANCE: The search returned 1802 articles and eight studies were included for analysis. Populations targeted were primarily overweight or obese subfertile women seeking reproductive assistance, with few community-based studies and none including men. MA showed greater reduction in weight (n = 3, P < 0.00001, mean difference: -3.48 kg, 95% CI: -4.29, -2.67, I2 = 0%) and BMI (n = 2, P < 0.00001, mean difference: -1.40 kg/m2, 95% CI: -1.95, -0.84, I2 = 24%) with intervention. The only significant fertility outcome was an increased natural pregnancy rate (n = 2, P = 0.003, odds ratio: 1.87, CI: 1.24, 2.81, I2 = 0%). No differences were observed for ART adverse events, clinical pregnancy, pregnancy complications, delivery complications, live birth, premature birth, birth weight, neonatal mortality or anxiety. Risk of bias were high for three studies, moderate for three studies and low for two studies, Attrition bias was moderate or high in majority of studies. LIMITATIONS, REASONS FOR CAUTION: Results were limited to subfertile or infertile women who were overweight or obese undergoing ART with no studies in men. The heterogeneous nature of the interventions in terms of duration and regimen means no conclusions could be made regarding the method or components of optimal lifestyle intervention. Attrition bias itself is an important factor that could affect efficacy of interventions. WIDER IMPLICATIONS OF THE FINDINGS: Existing preconception lifestyle interventions primarily targeted overweight and obese subfertile women undergoing ART with a focus on weight loss. It is important to note that natural conception increased with lifestyle intervention. This emphasizes the need for further research exploring optimal components of preconception lifestyle interventions in the broader population and on the optimal nature, intensity and timing of interventions. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest declared. C.L.H. is a National Heart Foundation Postdoctoral Research Fellow. B.H. is funded by an Alfred Deakin Postdoctoral Research Fellowship. H.J.T. and B.W.M. hold NHMRC Practitioner fellowships. L.J.M. is supported by a SACVRDP Fellowship; a program collaboratively funded by the NHF, the South Australian Department of Health and the South Australian Health and Medical Research Institute. PROSPERO REGISTRATION NUMBER: CRD42015023952.

Weight management practices associated with PCOS and their relationships with diet and physical activity.

STUDY QUESTION: Do weight management practices differ in women with and without PCOS? SUMMARY ANSWER: Women in the general population with self-reported PCOS are more likely to be using healthy weight management practices and alternative non-lifestyle measures for weight management than women without PCOS. WHAT IS KNOWN ALREADY: Lifestyle management is the first-line treatment in PCOS. However, the specific weight management practices used by women with PCOS and their effect on diet and physical activity are unclear. STUDY DESIGN, SIZE, DURATION: The study was a population-based observational cross-sectional study involving women in the 1973-1978 cohort (n = 7767 total; n = 556 with PCOS, n = 7211 without PCOS). PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with and without self-reported PCOS were included. Self-reported outcome measures included healthy lifestyle-related or alternative non-lifestyle-related (e.g. laxatives or smoking) weight management practices, dietary intake and physical activity. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS were more likely to be following both healthy [reducing meal or snack size (odds ratio (OR) 1.50, 95% CI 1.14, 1.96, P = 0.004) and reducing fat or sugar intake (OR 1.32, 95% CI 1.03, 1.69, P = 0.027) or following a low glycaemic index diet (OR 2.88, 95% CI 2.30, 3.59, P < 0.001)] and alternative [smoking (OR 1.60, 95% CI 1.02, 2.52, P = 0.043) or use of laxative, diet pills, fasting or diuretics (OR 1.45, 95% CI 1.07, 1.97, P = 0.017)] weight management practices than women without PCOS. In PCOS, the use of a range of healthy weight management practices was associated with increases in physical activity (P < 0.001), diet quality (P < 0.001), percentage protein intake (P < 0.001) and decreases in glycaemic index (P < 0.001), and percentages of fat (P = 0.001), saturated fat (P < 0.001) or fibre (P = 0.003). Use of alternative weight management practices was associated with decreases in diet quality. LIMITATIONS, REASONS FOR CAUTION: Limitations include the use of self-reported data for PCOS, height, weight, diet, physical activity and weight management behaviours. WIDER IMPLICATIONS OF THE FINDINGS: In PCOS, we should focus on improving healthy weight practices across both diet quality and quantity, and on assessing alternative weight practices and their potential adverse effect on dietary intake. STUDY FUNDING/COMPETING INTEREST(S): L.M. is supported by a South Australian Cardiovascular Research Development Program Fellowship (ID AC11S374); a program collaboratively funded by the National Heart Foundation, the South Australian Department of Health and the South Australian Health and Medical Research Institute. H.T. is supported by the NHMRC. S.A.M. is supported by an NHMRC Career Development Fellowship Level 2, ID1104636 and was previously supported by an ARC Future Fellowship (2011-2015, FT100100581). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

The association between Polycystic Ovary Syndrome (PCOS) and metabolic syndrome: a statistical modelling approach.

OBJECTIVE: Polycystic ovary syndrome (PCOS) affects 12-21% of women. Women with PCOS exhibit clustering of metabolic features. We applied rigorous statistical methods to further understand the interplay between PCOS and metabolic features including insulin resistance, obesity and androgen status. DESIGN: Retrospective cross-sectional analysis. PATIENTS: Women with PCOS attending reproductive endocrine clinics in South Australia for the treatment of PCOS (n = 172). Women without PCOS (controls) in the same Australian region (n = 335) from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), a national population-based study (age- and BMI-matched within one standard deviation of the PCOS cohort). MEASUREMENTS: The factor structure for metabolic syndrome for women with PCOS and control groups was examined, specifically, the contribution of individual factors to metabolic syndrome and the association of hyperandrogenism with other metabolic factors. RESULTS: Women with PCOS demonstrated clustering of metabolic features that was not observed in the control group. Metabolic syndrome in the PCOS cohort was strongly represented by obesity (standardized factor loading = 0·95, P < 0·001) and insulin resistance factors (loading = 0·92, P < 0·001) and moderately by blood pressure (loading = 0·62, P < 0·001) and lipid factors (loading = 0·67, P = 0·002). On further analysis, the insulin resistance factor strongly correlated with the obesity (r = 0·70, P < 0·001) and lipid factors (r = 0·68, P < 0·001) and moderately with the blood pressure factor (loading = 0·43, P = 0·002). The hyperandrogenism factor was moderately correlated with the insulin resistance factor (r = 0·38, P < 0·003), but did not correlate with any other metabolic factors. CONCLUSIONS: PCOS women are more likely to display metabolic clustering in comparison with age- and BMI-matched control women. Obesity and insulin resistance, but not androgens, are independently and most strongly associated with metabolic syndrome in PCOS.

Obesity and polycystic ovary syndrome.

Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles.

Vitamin D is independently associated with depression in overweight women with and without PCOS.

BACKGROUND: Depression, anxiety, and inflammation are common in polycystic ovary syndrome (PCOS). Inflammation may adversely impact on mood and vitamin D has been associated with both mood disorders and inflammation in the general population, but these relationships have not been studied in PCOS. The aim of this study was to investigate the association among 25 hydroxy-Vitamin D (25OHVD) status, anxiety, depression, and inflammation in women with and without PCOS. METHODS: Cross-sectional study in overweight or obese premenopausal women with (n = 50) and without (n = 23) PCOS. Primary outcome measures were 25OHVD, mood (Hospital Anxiety and Depression questionnaire), and inflammation (highly sensitive C-reactive protein (hsCRP)). RESULTS: Vitamin D deficiency (25OHVD<50 nmol/L) (46% versus 39%, p = 0.311) and 25OHVD (50.4 ± 22.2 nmol/L versus 51.6 ± 19.0 nmol/L, p = 0.828) were not significantly different in women with and without PCOS. For all women combined, 25OHVD was the only significant independent predictor of depression (ß = -0.063 ± 0.021, p = 0.005) and hsCRP (ß = -0.041 ± 0.015, p = 0.010). CONCLUSIONS: Vitamin D deficiency is common in both women with and without PCOS with no differences between the groups. Vitamin D is independently associated with depression and inflammation in overweight women both with and without PCOS. Further investigation to clarify the interrelationship among vitamin D, inflammation and depression is required to identify optimal prevention and treatment strategies for psychological and metabolic dysfunction in PCOS.

Acceptability of delivery modes for lifestyle advice in a large scale randomised controlled obesity prevention trial.

BACKGROUND: Preventing obesity is an international health priority and women living in rural communities are at an increased risk of weight gain. Lifestyle programs are needed as part of a comprehensive approach to prevent obesity. Evaluation provides a unique opportunity to investigate and inform improvements in lifestyle program implementation strategies. The Healthy Lifestyle Program for rural women (HeLP-her Rural) is a large scale, cluster randomized control trial, targeting the prevention of weight gain. This program utilises multiple delivery modes for simple lifestyle advice (group sessions, phone coaching, text messages, and an interactive program manual). Here, we describe the acceptability of these various delivery modes. METHODS: A mixed-method process evaluation was undertaken measuring program fidelity, recruitment strategies, dose delivered, program acceptability and contextual factors influencing program implementation. Data collection methodologies included qualitative semi-structured interviews for a sub-group of intervention participants [n = 28] via thematic analysis and quantitative methods (program checklists and questionnaires [n = 190]) analysed via chi square and t-tests. RESULTS: We recruited 649 women from 41 rural townships into the HeLP-her Rural program with high levels of program fidelity, dose delivered and acceptability. Participants were from low socioeconomic townships and no differences were detected between socioeconomic characteristics and the number of participants recruited across the towns (p = 0.15). A face-to-face group session was the most commonly reported preferred delivery mode for receiving lifestyle advice, followed by text messages and phone coaching. Multiple sub-themes emerged to support the value of group sessions which included: promoting of a sense of belonging, mutual support and a forum to share ideas. The value of various delivery modes was influenced by participant's various needs and learning styles. CONCLUSION: This comprehensive evaluation reveals strong implementation fidelity and high levels of dose delivery. We demonstrate reach to women from relatively low income rural townships and highlight the acceptability of low intensity healthy lifestyle programs with mixed face-to-face and remote delivery modes in this population. Group education sessions were the most highly valued component of the intervention, with at least one face-to-face session critical to successful program implementation. However, lifestyle advice via multiple delivery modes is recommended to optimise program acceptability and ultimately effectiveness. TRIAL REGISTRY: Australia & New Zealand Clinical Trial Registry. Trial number ACTRN12612000115831, date of registration 24/01/2012.

Contraception use and pregnancy outcomes in women with polycystic ovary syndrome: data from the Australian Longitudinal Study on Women's Health.

STUDY QUESTION: Do contraception use, pregnancy outcome and number of children differ in women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Women with PCOS were less likely to report use of contraception and more likely to report a miscarriage, whilst number of children was similar between groups. WHAT IS KNOWN ALREADY: The oral contraceptive pill is used in the management of PCOS, but the patterns of contraception use in women with PCOS is not known. In women with PCOS who undergo assisted reproduction, the risk of pregnancy loss appears higher, yet pregnancy loss and family size among community-based women with PCOS is not known. STUDY DESIGN, SIZE AND DURATION: This is a cross-sectional analysis of a longitudinal cohort study. Mailed survey data were collected at five time points (years 1996, 2000, 2003, 2006 and 2009). Data from respondents to Survey 4 (2006), aged 28-33 (n = 9145, 62% of the original cohort aged 18-23 years) were analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted in a general community setting. Data from participants who responded to the questions on PCOS, contraception and pregnancy outcome were analysed. The main outcome measures were self-reported PCOS, body mass index (BMI), contraception use, pregnancy loss and number of children. MAIN RESULTS AND THE ROLE OF CHANCE: In women aged 28-33 years, women with PCOS were less likely to be using contraception (61 versus 79%, P < 0.001) and more likely to be trying to conceive (56 versus 45%, P < 0.001), compared with women not reporting PCOS. A greater proportion of women with PCOS reported pregnancy loss (20 versus 15%, P = 0.003). PCOS was not independently associated with pregnancy loss; however, BMI was independently associated with pregnancy loss in the overweight and obese groups (OR 1.2, 95% CI 1.04-1.4, P = 0.02 and OR 1.4, 95% CI 1.1-1.6, P = 0.001, respectively). Fertility treatment use was also independently associated with pregnancy loss (adjusted OR 3.2, 95% CI 2.4-4.2, P < 0.001). There was no significant difference in number of children between women with and without PCOS. LIMITATIONS, REASON FOR CAUTION: PCOS, contraception use and pregnancy outcome data were self-reported. Attrition occurred, but is reasonable compared with similar longitudinal cohort studies. WIDER IMPLICATIONS OF THE FINDINGS: This community-based cohort aged 28-33 years provides insights into the contraceptive use, pregnancy loss and family size of a large cohort of unselected women. Women reporting PCOS had lower rates of contraception use and were more likely to be currently trying to conceive, suggesting that they may be aware of potential fertility challenges, yet in those not planning to conceive, contraceptive use was low and further education may be required. Despite prior reports of higher rates of pregnancy loss in PCOS, usually from infertility services, in this community-based population, PCOS was not independently associated with pregnancy loss, yet independent risk factors for pregnancy loss included higher BMI, were higher in PCOS. The number of children per woman was similar in the both groups, albeit with more infertility treatment in PCOS. This may reassure women with PCOS that with access to fertility treatment, family sizes appear similar to women not reporting PCOS.

Sleep difficulty mediates effects of vasomotor symptoms on mood in younger breast cancer survivors.

OBJECTIVE: Treatment-induced early menopause occurs in > 80% of premenopausal women diagnosed with breast cancer. This study explored the relationship between vasomotor symptoms (VMS), sleep and mood in women aged 40-51 years with non-metastatic breast cancer. METHODS: Cross-sectional study using validated questionnaires (Greene Climacteric scale and Hospital Anxiety and Depression Scale, HADS). Women (n = 114) were recruited from the community and hospital outpatient clinics. Frequency determination and structural equation modeling (SEMod) were used to examine the relationship between the latent variables: VMS, anxiety, and depression, and the indicator variable: difficulty sleeping. RESULTS: Participants' mean age was 47 years and 94% became menopausal after breast cancer diagnosis. Difficulty sleeping was reported by 82% of women with 46% reporting (Likert scale) 'quite a bit/extremely'. Most women reported night sweats (77% of women: 47% reporting 'quite a bit/extremely') and hot flushes (84% of women: 50% reporting 'quite a bit/extremely'). HADS scores indicated clinically relevant depression and anxiety in 98% and 99% of women, respectively. SEMod revealed that VMS contributed to difficulty sleeping (standardized coefficient = 0.54; p < 0.001) and difficulty sleeping mediated the relationship between VMS and anxiety (standardized coefficient = 0.34; p = 0.03). However, difficulty sleeping did not have a significant direct impact on depression (standardized coefficient = -0.03; p = 0.8), although anxiety was a strong predictor of depression (standardized coefficient = 0.83; p = 0.015). CONCLUSIONS: VMS, sleep and mood disturbance are commonly experienced by younger women with breast cancer. Using SEMod, we demonstrate for the first time that VMS may directly influence sleep in these women. VMS may have an indirect effect on mood, partly mediated by sleep difficulty.

The contribution of diet, physical activity and sedentary behaviour to body mass index in women with and without polycystic ovary syndrome.

STUDY QUESTION: What is the contribution of diet, physical activity and sedentary behaviour to body mass index (BMI) in women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: PCOS status, higher energy intake and glycaemic index and lower physical activity were independently associated with BMI. WHAT IS KNOWN ALREADY: Obesity worsens the clinical features of PCOS and women with PCOS have an elevated prevalence of overweight and obesity. It is not known whether there is a contribution of lifestyle factors such as dietary intake, physical activity or sedentary behaviour to the elevated prevalence of obesity in PCOS. STUDY DESIGN, SIZE, DURATION: This study is a population-based observational study with data currently collected at 13 year follow-up. The study commenced in 1996. For this analysis, data are analysed at one time point corresponding to the Survey 5 of the cohort in 2009. At this time 8200 participants remained (58% retention of baseline participants) of which 7466 replied to the questionnaire; 409 self-reported a diagnosis of PCOS and 7057 no diagnosis of PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Australian women born in 1973-1978 from the Australian Longitudinal Study on Women's Health. MAIN RESULTS AND THE ROLE OF CHANCE: Mean BMI was higher in women with PCOS compared with non-PCOS (29.3 ± 7.5 versus 25.6 ± 5.8 kg/m(2), P < 0.001). Women with PCOS reported a better dietary intake (elevated diet quality and micronutrient intake and lower saturated fat and glycaemic index intake) but increased energy intake, increased sitting time and no differences in total physical activity compared with non-PCOS. PCOS status, higher energy intake and glycaemic index and lower physical activity, as well as age, smoking, alcohol intake, occupation, education and country of birth, were independently associated with BMI. LIMITATIONS, REASONS FOR CAUTION: The weaknesses of this study include the self-reported diagnosis of PCOS, and the women not reporting PCOS not having their control status clinically verified which is likely to underrepresent the PCOS population. We are also unable to determine if lifestyle behaviours contributed to the PCOS diagnosis or were altered in response to diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: The strengths of this study include the community-based nature of the sample which minimizes selection bias to include women with a variety of clinical presentations. These results are therefore generalizable to a broader population than the majority of research in PCOS examining this research question which are performed in clinic-based populations. This study is in agreement with the literature that PCOS is independently associated with elevated BMI. We provide new insights that diet quality is subtly improved but that sedentary behaviour is elevated in PCOS and that PCOS status, higher energy intake and glycaemic index and lower physical activity are independently associated with BMI. STUDY FUNDING/COMPETING INTEREST(S): L.J.M. was supported by a South Australian Cardiovascular Research Development Program (SACVRDP) Fellowship (AC11S374); a program collaboratively funded by the National Heart Foundation of Australia, the South Australian Department of Health and the South Australian Health and Medical Research Institute, S.A.M. was funded by an Australian Research Council Future Fellowship (FT100100581), S.Z. was funded by a Heart Foundation Career Development Fellowship (ID CR10S5330) and H.J.T. was funded by an NHMRC fellowship (ID 545888). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Diabetes care provision: barriers, enablers and service needs of young adults with Type 1 diabetes from a region of social disadvantage.

AIMS: To determine the barriers to and enablers of engaging with specialist diabetes care and the service requirements of young adults with Type 1 diabetes mellitus from a low socio-economic, multicultural region. METHODS: A cross-sectional survey targeted 357 young adults with Type 1 diabetes, aged 18-30 years. Participants completed questions about barriers/enablers to accessing diabetes care and service preferences, self-reported HbA(1c), plus measures of diabetes-related distress (Problem Areas in Diabetes), depression/anxiety (Hospital Anxiety and Depression Scale), and illness perceptions (Brief Illness Perceptions Questionnaire). RESULTS: Eighty-six (24%) responses were received [55 (64%) female; mean ± sd age 24 ± 4 years; diabetes duration 12 ± 7 years; HbA(1c) 68 ± 16 mmol/mol (8.4 ± 1.5%)]. Logistical barriers to attending diabetes care were reported; for example, time constraints (30%), transportation (26%) and cost (21%). However, 'a previous unsatisfactory diabetes health experience' was cited as a barrier by 27%. Enablers were largely matched to overcoming these barriers. Over 90% preferred a multidisciplinary team environment, close to home, with after-hours appointment times. Forty per cent reported severe diabetes-related distress, 19% reported moderate-to-severe depressive symptoms and 50% reported moderate-to-severe anxiety. CONCLUSIONS: Among these young adults with Type 1 diabetes, glycaemic control was suboptimal and emotional distress common. They had identifiable logistical barriers to accessing and maintaining contact with diabetes care services, which can be addressed with flexible service provision. A substantial minority were discouraged by previous unsatisfactory experiences, suggesting health providers need to improve their interactions with young adults. This research will inform the design of life-stage-appropriate diabetes services targeting optimal engagement, access, attendance and ultimately improved healthcare outcomes in this vulnerable population.

Differences in clinician understanding and management of early menopause after breast cancer.

OBJECTIVE: Investigation of clinicians' understanding of early menopause diagnosis/management in women with breast cancer. METHODS: A cross-sectional study of 176 randomly recruited Australian clinicians (35 gynecologists, 35 endocrinologists, 36 oncologists, 35 breast surgeons and 35 general practitioners (GPs)) involved in the care of women with breast cancer. This questionnaire study utilized an index case to assess understanding of early menopause diagnosis and management. Analysis involved descriptive statistics, χ² tests and Student's t-test. RESULTS: Significant differences between clinician groups regarding diagnostic criteria for early menopause were observed; gynecologists, endocrinologists and GPs selected amenorrhea > 12 months, whereas oncologists and breast surgeons selected elevated serum follicle stimulating hormone level (p < 0.05). Non-hormonal treatment was preferred by most clinician groups. Complementary/alternative medicines were more commonly prescribed by breast surgeons (57%), gynecologists (54%) and endocrinologists (49%) compared to oncologists (28%) or GPs (9%) (p = 0.0001). Exercise (63%) and nutrition (66%) were selected by most gynecologists for treatment of hot flushes, whereas endocrinologists (91%), oncologists (94%), breast surgeons (69%) and GPs (63%) prescribed venlafaxine. Hormone therapy was mainly prescribed by breast surgeons (43%) compared to other groups (p = 0.001). Most clinicians reported that the main problem with menopausal therapies was failure to resolve hot flushes. Exercise, lifestyle and stress management were recommended by all clinician groups for treatment of anxiety/depression. CONCLUSION: This exploratory study demonstrated a lack of consensus between clinician groups in their investigation, diagnosis and management of early menopause in women with breast cancer, with implications for both diagnosis and treatment.

Sex hormone binding globulin, but not testosterone, is associated with the metabolic syndrome in overweight and obese women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and an increased risk of Type 2 diabetes and cardiovascular disease. Decreased SHBG and elevated testosterone are associated with metabolic syndrome and glucose intolerance in women. AIM: The aim of this study was to assess the relationship between SHBG and testosterone and metabolic syndrome and glucose intolerance in PCOS. MATERIAL/SUBJECTS AND METHODS: Cross-sectional study in overweight and obese premenopausal non-diabetic women with PCOS (no.=178: no.=55 metabolic syndrome, no.=16 glucose intolerance). Data were analyzed by multiple regression with metabolic syndrome, oral glucose tolerance test (OGTT) glucose or SHBG as dependent variables and reproductive hormones, insulin resistance, glucose tolerance, lipids or C-reactive protein as independent variables. RESULTS: Metabolic syndrome was independently associated with body mass index [odds ratio (OR) 1.084 95% confidence interval (CI) 1.034-1.170, p=0.015] and SHBG (OR 0.961 95% CI 0.932-0.995, p=0.018). Glucose tolerance was independently associated with OGTT insulin (ß=0.418, p<0.001), age (ß=0.154, p=0.033) and PRL (ß=-0.210, p=0.002). SHBG was independently associated with OGTT insulin (ß=-0.216, p=0.014) and PCOS diagnostic criteria (ß=0.197, p=0.010). CONCLUSIONS: SHBG, but not testosterone, is independently associated with metabolic syndrome in overweight women with PCOS and is associated with insulin resistance and PCOS diagnostic criteria.

Effect of exercise training on insulin sensitivity, mitochondria and computed tomography muscle attenuation in overweight women with and without polycystic ovary syndrome.

AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is an insulin resistant (IR) state. Increased skeletal muscle lipid content and impaired mitochondrial biogenesis have been implicated in the pathogenesis of IR. We investigated whether differences in these variables explain the IR of women affected by PCOS and whether improvements in IR with exercise are reflected by changes in these variables. METHODS: Sixteen PCOS and 13 non-PCOS overweight women were assessed, and eight PCOS and seven non-PCOS women were reassessed after 12 weeks of moderate and vigorous exercise training. Outcomes included insulin sensitivity (glucose infusion rate [GIR]), skeletal muscle gene expression and protein abundance, enzyme activity of selected mitochondrial components, and computed tomography (CT) attenuation-estimated muscle lipid. RESULTS: GIR was lower in women with PCOS versus those without (p = 0.01) and increased with exercise in both groups. Baseline CT muscle attenuation suggested a trend to less muscle lipid in PCOS, which increased with exercise training, with a difference in the change in muscle lipid (p = 0.01, age-corrected), compared with non-PCOS women. GIR correlated with PGC1A gene expression across the whole group; skeletal muscle expression of mitochondrial biogenesis markers was not different between groups at baseline, or after training. Neither lipid changes nor mitochondrial changes correlated with changes in GIR. CONCLUSIONS/INTERPRETATION: Differences in IR in women with and without PCOS were not explained by differences in skeletal muscle lipid or mitochondrial parameters. Improvements in IR with exercise were dissociated from mitochondrial parameters. CT muscle attenuation suggested a differential capacity of PCOS muscle to store lipid compared with non-PCOS. TRIAL REGISTRATION: Clinicaltrials.gov ISRCTN84763265. FUNDING: National Health & Medical Research Council (Grant number 606553), Monash University and The Jean Hailes Foundation.

Psychological parameters in the reproductive phenotypes of polycystic ovary syndrome.

BACKGROUND: The aim of this study was to assess the psychological features in women with different polycystic ovary syndrome (PCOS) phenotypes [National Institute of Health (NIH) and non-NIH diagnostic criteria] and women without PCOS. METHODS: An observational, cross-sectional study compared overweight (BMI ≥ 25 kg/m(2)) premenopausal women with PCOS (n = 29 NIH and n = 25 non-NIH) and controls (n = 27). Anxiety and depression were compared between women with NIH or non-NIH PCOS and women without PCOS. Health-related quality of life (HRQoL) domains related to emotions, body hair, weight, infertility and menstrual problems were compared between women with NIH and non-NIH PCOS. RESULTS: Overall, women with PCOS had worse anxiety (P = 0.007) and depression (P = 0.048) compared with women without PCOS. Both women with NIH PCOS and non-NIH PCOS presented more often with moderate anxiety (P = 0.005 and P = 0.01, respectively) compared with women without PCOS. Women with NIH PCOS had worse HRQoL related to infertility (P = 0.012), emotions (P = 0.02) and weight (P = 0.016). No significant differences were observed between the two PCOS phenotypes for HRQoL domains related to body hair or menstrual problems. Both NIH (ß = 0.30, P = 0.024) and non-NIH (ß = 0.32, P = 0.016) PCOS status predicted anxiety, whereas age (ß = 0.35, P = 0.008) and free androgen index (ß = 0.31, P = 0.027) predicted depression. CONCLUSIONS: PCOS is associated with anxiety and depression. Non-NIH phenotypes present with similar psychological profiles to NIH PCOS, indicating increased psychological dysfunction in PCOS, even in milder reproductive phenotypes. However, women with NIH PCOS appear to have worse HRQoL in some areas than women with non-NIH PCOS. Psychological function and HRQoL should be considered in all women with PCOS.