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.

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.

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.

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.

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.

Inositol treatment of anovulation in women with polycystic ovary syndrome: a meta-analysis of randomised trials.

Polycystic ovary syndrome is a common cause of anovulation and infertility, and a risk factor for development of metabolic syndrome and endometrial cancer. Systematic review and meta-analysis of randomised controlled trials (RCT) that evaluated the effects of inositol as an ovulation induction agent. We searched MEDLINE, EMBASE, Cochrane and ISI conference proceedings, Register and Meta-register for RCT and WHO trials' search portal. We included studies that compared inositol with placebo or other ovulation induction agents. Quality of studies was assessed for risk of bias. Results were pooled using random effects meta-analysis and findings were reported as relative risk or standardised mean differences. We included ten randomised trials. A total of 362 women were on inositol (257 on myo-inositol; 105 on di-chiro-inositol), 179 were on placebo and 60 were on metformin. Inositol was associated with significantly improved ovulation rate (RR 2.3; 95% CI 1.1-4.7; I2 = 75%) and increased frequency of menstrual cycles (RR 6.8; 95% CI 2.8-16.6; I2 = 0%) compared with placebo. One study reported on clinical pregnancy rate with inositol compared with placebo (RR 3.3; 95% CI 0.4-27.1), and one study compared with metformin (RR 1.5; 95% CI 0.7-3.1). No studies evaluated live birth and miscarriage rates. Inositol appears to regulate menstrual cycles, improve ovulation and induce metabolic changes in polycystic ovary syndrome; however, evidence is lacking for pregnancy, miscarriage or live birth. A further, well-designed multicentre trial to address this issue to provide robust evidence of benefit is warranted. TWEETABLE ABSTRACT: Inositols improve menstrual cycles, ovulation and metabolic changes in polycystic ovary syndrome.

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.

The association of the lipidomic profile with features of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI >20 kg/m2; n = 92 with PCOS, n = 64 without PCOS). Outcomes included the association between the plasma lipidomic profile (325 lipid species (24 classes) using liquid chromatography mass spectrometry) and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex hormone-binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes (4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely (trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions.

Knowledge and attitudes of health professionals regarding menopausal hormone therapies.

OBJECTIVE: To evaluate the knowledge and attitudes of Australian health professionals (HPs) including general practitioners (GPs), gynecologists and endocrinologists, to menopausal hormone therapy (MHT). METHODS: Participants were recruited from medical societies/colleges and a national GP conference. An online survey containing devised and previously published questions was used. Data analysis included frequencies, ANOVA, χ2 and regression analysis. RESULTS: A total of 745/888 responses were analyzed. Fewer HPs (52%) reported being knowledgeable regarding non-hormonal therapies compared with menopause physiology or MHT (72%), with no significant knowledge differences between specialties. Most HPs (91%) would offer MHT to symptomatic menopausal women. The combined oral contraceptive pill (52%) was preferred for women with premature menopause. Transdermal MHT was preferred for women >50 years, although differences were observed between specialties (p = 0.005). HPs varied regarding duration of MHT for women with premature menopause (p = 0.009) and women over 50 years (p = 0.001). Menopause society members were more likely to prescribe MHT and for longer duration (p < 0.05). Consumer concern regarding breast cancer was considered the main barrier in prescribing MHT. CONCLUSIONS: Although most HPs will recommend MHT, when indicated, for symptomatic menopausal women, variations exist between specialties in prescribing practices. HPs' knowledge gaps and perceived consumer concerns are barriers to prescribing MHT.

Gaps and barriers in health-care provision for co-morbid diabetes and chronic kidney disease: a cross-sectional study.

BACKGROUND: Patients with diabetes and chronic kidney disease (CKD) are a complex subset of the growing number of patients with diabetes, due to multi-morbidity. Gaps between recommended and received care for diabetes and chronic kidney disease (CKD) are evident despite promulgation of guidelines. Here, we document gaps in tertiary health-care, and the commonest patient-reported barriers to health-care, before exploring the association between these gaps and barriers. METHODS: This cross-sectional study recruited patients with diabetes and CKD (eGFR < 60 mL/min/1.73 m2) across 4 large hospitals. For each patient, questionnaires were completed examining clinical data, recommended care, and patient-reported barriers limiting health-care. Descriptive statistics, subgroup analyses by CKD stage and hospital, and analyses examining the relationship between health-care gaps and barriers were performed. RESULTS: 308 patients, of mean age 66.9 (SD 11.0) years, and mostly male (69.5%) and having type 2 diabetes (88.0%), participated. 49.1% had stage 3, 24.7% stage 4 and 26.3% stage 5 CKD. Gaps between recommended versus received care were evident: 31.9% of patients had an HbA1c ≥ 8%, and 39.3% had a measured blood pressure ≥ 140/90 mmHg. The commonest barriers were poor continuity of care (49.3%), inadequate understanding/education about CKD (43.5%), and feeling unwell (42.6%). However, barriers associated with a failure to receive items of recommended care were inadequate support from family and friends, conflicting advice from and poor communication amongst specialists, the effect of co-morbidities on self-management and feeling unmotivated (all p < 0.05). CONCLUSIONS: Barriers to health-care varied across CKD stages and hospitals. Barriers associated with a deviation from recommended care were different for different items of care, suggesting that specific interventions targeting each item of care are required.

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.

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.

Young women's psychological distress after a diagnosis of polycystic ovary syndrome or endometriosis.

STUDY QUESTION: Do young women with polycystic ovary syndrome (PCOS) or endometriosis report more psychological distress than their peers without a history of these conditions? SUMMARY ANSWER: Young women (aged 18-23 years) with PCOS or endometriosis had a greater risk of moderate to severe psychological distress than women without a history of these conditions. WHAT IS KNOWN ALREADY: Psychological distress appears common among women with PCOS and endometriosis. However, population-based studies that examine the psychological outcomes for adolescents and young women are generally absent from the literature. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of data collected from 17 015 young, Australian women participating in a national, longitudinal cohort study. Women were first surveyed in 2012-2013 when they were aged 18-23 years. In 2014, women completed the second survey when they were aged 19-24 years and 11324 (67%) women responded. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analysed data from 11 238 women who participated in both Surveys 1 and 2 and who responded to questions about PCOS and endometriosis. Using logistic regression, we compared the odds of moderate to severe psychological distress at Surveys 1 and 2 for women reporting a recent diagnosis (within the last 12 months) of PCOS or endometriosis and women with a pre-existing diagnosis, with that for women without a history of these conditions. MAIN RESULTS AND THE ROLE OF CHANCE: At Survey 2, around 60% of women reporting a diagnosis of PCOS or endometriosis had moderate to severe levels of psychological distress. Compared to women without a history of these conditions, the odds of moderate to severe psychological distress at Survey 2 were significantly higher for women recently diagnosed with PCOS [Adjusted Odds Ratio (AOR) = 1.62, 95% CI = 1.21-2.18] or endometriosis (AOR= 1.77; 95% CI = 1.20-2.63) and for women with a pre-existing diagnosis of PCOS (AOR = 1.57, 95% CI = 1.30-1.89) or endometriosis (AOR = 1.61; 95% CI = 1.26-2.06). Women recently diagnosed with PCOS or endometriosis also had a greater likelihood of moderate to severe distress in the year prior to their diagnosis. The association between PCOS and psychological distress was attenuated when adjusting for BMI, but hormonal contraceptive use did not attenuate the risk of distress among the women with PCOS or endometriosis. LIMITATIONS, REASONS FOR CAUTION: All data were self-reported and, therefore, the diagnoses of PCOS or endometriosis were not confirmed by a medical practitioner. WIDER IMPLICATIONS OF THE FINDINGS: Health professionals should be aware of the potential psychosocial and healthcare needs among young women with these conditions, particularly women with PCOS who are obese. While hormonal contraceptives may help to regulate the hormonal aspects of these conditions, they do not appear to reduce women's psychological distress. Because psychological distress among the young women in this study remained elevated even after diagnosis, this supports the need for multidisciplinary health care to help women adjust to their diagnosis and treatment regimens and facilitate positive, long-term mental health outcomes. Future research that examines medical and psychosocial sources of distress for young women with PCOS and endometriosis is needed. STUDY FUNDING/COMPETING INTERESTS: I.J.R. was supported by an Australian National Health and Medical Research Council Centre for Research Excellence (grant number: APP1000986). G.D.M. is funded by the Australian Research Council Future Fellowship (FT120100812). The Australian Longitudinal Study on Women's Health is funded by the Australian Government Department of Health. H.T. is supported by an Australian National Health and Medical Research Council Practitioner Fellowship. The authors declare that no competing interests exist. TRIAL REGISTRATION NUMBER: N/A.

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.

Vitamin D and cardiometabolic risk factors and diseases.

Obesity, type 2 diabetes, and cardiovascular disease (CVD) are the most common preventable causes of morbidity and mortality worldwide. Insulin resistance, which is a shared feature in these conditions, is also strongly linked to the development of polycystic ovary syndrome (PCOS), which is the most common endocrine disease in women of reproductive age and a major cause of infertility. Vitamin D deficiency has reached epidemic proportions worldwide, primarily due to the shift to sedentary, indoor lifestyles and sun avoidance behaviours to protect against skin cancer. In recent years, vitamin D deficiency has been implicated in the aetiology of type 2 diabetes, PCOS and CVD, and has been shown to be associated with their risk factors including obesity, insulin resistance, hypertension, as well as chronic low-grade inflammation. Treating vitamin D deficiency may offer a feasible and cost-effective means of reducing cardiometabolic risk factors at a population level in order to prevent the development of type 2 diabetes and CVD. However, not all intervention studies show that vitamin D supplementation alleviates these risk factors. Importantly, there is significant heterogeneity in existing studies with regards to doses and drug regimens used, populations studied (i.e. vitamin D deficient or sufficient), and the lengths of supplementation, and only few studies have directly examined the effect of vitamin D on insulin secretion and resistance with the use of clamp methods. Therefore, there is a need for well-designed large scale trials to clarify the role of vitamin D supplementation in the prevention of type 2 diabetes, PCOS, and CVD.

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.

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.