Transition between cardiometabolic conditions and body weight among women: which paths increase the risk of diabetes and cardiovascular diseases?

Previous studies investigated the association of body weight and hypertension with risk of incident cardiometabolic multimorbidity. Our aim was to estimate the risk of diabetes and cardiovascular disease later in life for subjects with different progression patterns of overweight, obesity, and hypertension in mid-life. This was a prospective cohort study in which data from 12,784 participants in the Australian Longitudinal Study on Women's Health were used. Multistate model was used to study the progression pattern of overweight, obesity, hypertension, diabetes, and cardiovascular disease over the life course. The cumulative incidence of diabetes and cardiovascular disease up to the age of 73 was estimated for women with different patterns of other conditions. The six most common paths and corresponding cumulative incidences for diabetes were overweight 5.1%, obesity 11.5%, hypertension 6.9%, progression from overweight to obesity 8.2%, overweight and hypertension 12.1%, and obesity and hypertension 36.8%. For women with diabetes and other conditions, the cumulative incidence of cardiovascular disease (heart disease or stroke) as the next immediate condition was 22.4%. The corresponding figure for women who only had a report of diabetes but did not have high body weight or hypertension was 8.3%. The higher risk of transition from healthy state to a cardiometabolic condition was associated with low education, income stress, smoking, not drinking alcohol (compared to low drinkers), physical inactivity, and high perceived stress. Women with obesity and hypertension in middle-age had a substantially higher risk of developing diabetes and cardiovascular disease than women without these potentially preventable conditions.

Association of infertility and recurrent pregnancy loss with the risk of dementia.

Emerging evidence has shown the association between female reproductive histories (e.g., menarche age, parity, premature and early menopause) and the risk of dementia. However, little attention has been given to infertility and pregnancy loss. To examine the associations of infertility, recurrent miscarriages, and stillbirth with the risk of dementia, this study used data from four cohorts in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events. Women with data on at least one of the reproductive exposures of interest, dementia, and all covariates were included. Histories of infertility, miscarriage, and stillbirth were self-reported. Dementia (including Alzheimer's disease) was identified through surveys, aged care, pharmaceutical, hospital, and death registry data. Cause-specific Cox regression models were used to estimate the hazard ratios of dementia, accounting for well-established risk factors of dementia, study variability, and within-study correlation. Overall, 291,055 women were included at a median (interquartile range) age of 55.0 (47.0-62.0) at baseline. During the median (interquartile range) follow-up period of 13.0 (12.0-14.0) years, 3334 (1.2%) women developed dementia. Compared to women without stillbirth, a history of recurrent stillbirths (≥ 2) was associated with 64% higher risk of dementia (adjusted hazard ratio = 1.64, 95% confidence interval: 1.46-1.85). Compared to women without miscarriage, women with recurrent miscarriages (≥ 3) were at 22% higher risk of dementia (adjusted hazard ratio = 1.22, 95% confidence interval: 1.19-1.25). These findings suggest that recurrent stillbirths is a risk factor for dementia and may need to be considered in risk assessment of dementia in women.

Female reproductive histories and the risk of chronic obstructive pulmonary disease.

BACKGROUND: Female reproductive factors may influence the development of chronic obstructive pulmonary disease (COPD) through the female hormonal environment, but studies on this topic are limited. This study aimed to assess whether age at menarche, number of children, infertility, miscarriage, stillbirth and age at natural menopause were associated with the risk of COPD. METHODS: Women from three cohorts with data on reproductive factors, COPD and covariates were included. Cause specific Cox regression models were adjusted for birth year, race, educational level, body mass index and pack years of smoking, stratified by asthma, and incorporating interaction between birth year and time. Between cohort differences and within cohort correlations were taken into account. RESULTS: Overall, 2 83 070 women were included and 10 737 (3.8%) developed COPD after a median follow-up of 11 (IQR 10-12) years. Analyses revealed a U shaped association between age at menarche and COPD (≤11 vs 13: HR 1.17, 95% CI 1.11 to 1.23; ≥16 vs 13: HR 1.24, 95% CI 1.21 to 1.27). Women with three or more children (3 vs 2: HR 1.14, 95% CI 1.12 to 1.17; ≥4 vs 2: HR 1.34, 95% CI 1.28 to 1.40), multiple miscarriages (2 vs 0: HR 1.28, 95% CI 1.24 to 1.32; ≥3 vs 0: HR 1.36, 95% CI 1.30 to 1.43) or stillbirth (1 vs 0: HR 1.38, 95% CI 1.25 to 1.53; ≥2 vs 0: HR 1.67, 95% CI 1.32 to 2.10) were at a higher risk of COPD. Among postmenopausal women, earlier age at natural menopause was associated with an increased risk of COPD (<40 vs 50-51: HR 1.69, 95% CI 1.63 to 1.75; 40-44 vs 50-51: HR 1.42, 95% CI 1.38 to 1.47). CONCLUSIONS: Multiple female reproductive factors, including age at menarche, number of children, miscarriage, stillbirth, and age at natural menopause were associated with the risk of COPD.

Reducing antibiotic prescribing in general practice in Australia: a cluster randomised controlled trial of a multimodal intervention.

BACKGROUND: The health and economic burden of antimicrobial resistance (in Australia is significant. Interventions that help guide and improve appropriate prescribing for acute respiratory tract infections in the community represent an opportunity to slow the spread of resistant bacteria. Clinicians who work in primary care are potentially the most influential health care professionals to address the problem of antimicrobial resistance, because this is where most antibiotics are prescribed. METHODS: A cluster randomised trial was conducted comparing two parallel groups of 27 urban general practices in Queensland, Australia: 13 intervention and 14 control practices, with 56 and 54 general practitioners (GPs), respectively. This study evaluated an integrated, multifaceted evidence-based package of interventions implemented over a 6-month period. The evaluation included quantitative and qualitative components, and an economic analysis. RESULTS: A multimodal package of interventions resulted in a reduction of 3.81 prescriptions per GP per month. This equates to 1280.16 prescriptions for the 56GPs in the intervention practices over the 6-month period. The cost per prescription avoided was A$148. The qualitative feedback showed that the interventions were well received by the GPs and did not impact on consultation time. Providing GPs with a choice of tools might enhance their uptake and support for antimicrobial stewardship in the community. CONCLUSIONS: A multimodal package of interventions to enhance rational prescribing of antibiotics is effective, feasible and acceptable in general practice. Investment in antimicrobial stewardship strategies in primary care may ultimately provide the important returns for public health into the future.

Ethnic Differences in the Association Between Age at Natural Menopause and Risk of Type 2 Diabetes Among Postmenopausal Women: A Pooled Analysis of Individual Data From 13 Cohort Studies.

OBJECTIVE: To investigate associations between age at natural menopause, particularly premature ovarian insufficiency (POI) (natural menopause before age 40 years), and incident type 2 diabetes (T2D) and identify any variations by ethnicity. RESEARCH DESIGN AND METHODS: We pooled individual-level data of 338,059 women from 13 cohort studies without T2D before menopause from six ethnic groups: White (n = 177,674), Chinese (n = 146,008), Japanese (n = 9,061), South/Southeast Asian (n = 2,228), Black (n = 1,838), and mixed/other (n = 1,250). Hazard ratios (HRs) of T2D associated with age at menopause were estimated in the overall sample and by ethnicity, with study as a random effect. For each ethnic group, we further stratified the association by birth year, education level, and BMI. RESULTS: Over 9 years of follow-up, 20,064 (5.9%) women developed T2D. Overall, POI (vs. menopause at age 50-51 years) was associated with an increased risk of T2D (HR 1.31; 95% CI 1.20-1.44), and there was an interaction between age at menopause and ethnicity (P < 0.0001). T2D risk associated with POI was higher in White (1.53; 1.36-1.73), Japanese (4.04; 1.97-8.27), and Chinese women born in 1950 or later (2.79; 2.11-3.70); although less precise, the risk estimates were consistent in women of South/Southeast Asian (1.46; 0.89-2.40), Black (1.72; 0.95-3.12), and mixed/other (2.16; 0.83-5.57) ethnic groups. A similar pattern, but with a smaller increased risk of T2D, was observed with early menopause overall (1.16; 1.10-1.23) and for White, Japanese, and Chinese women born in 1950 or later. CONCLUSIONS: POI and early menopause are risk factors for T2D in postmenopausal women, with considerable variation across ethnic groups, and may need to be considered in risk assessments of T2D among women.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

What can death records tell us about multimorbidity?

BACKGROUND: Multimorbidity has been measured from many data sources which show that prevalence increases with age and is usually greater among women than men and in more recent periods. Analyses of multiple cause of death data have shown different patterns of multimorbidity associated with demographic and other characteristics. METHODS: Deaths in Australia among over 1.7 million decedents aged 55+ were stratified into three types: medically certified deaths, coroner-referred deaths with natural underlying causes and coroner-referred deaths with external underlying causes. Multimorbidity was measured by prevalence of ≥2 causes and analysed over three periods based on administrative changes: 2006-2012, 2013-2016 and 2017-2018. Poisson regression was used to examine the influence of gender, age and period. RESULTS: The prevalence of deaths with multimorbidity was 81.0% for medically certified deaths, 61.1% for coroner-referred deaths with natural underlying causes and 82.4% for coroner-referred deaths with external underlying causes. For medically certified deaths, multimorbidity increased with age: incidence rate ratio (IRR 1.070, 95% CI 1.068, 1.072) was lower for women than men (0.954, 95% CI 0.952, 0.956) and changed little over time. For coroner-referred deaths with natural underlying causes, multimorbidity showed the expected pattern increasing with age (1.066, 95% CI 1.062, 1.070) and being higher for women than men (1.025, 95% CI 1.015, 1.035) and in more recent periods. For coroner-referred deaths with external underlying causes, there were marked increases over time that differed by age group due to changes in coding processes. CONCLUSION: Death records can be used to examine multimorbidity in national populations but, like other data sources, how the data were collected and coded impacts the conclusions.

A new data driven method for summarising multiple cause of death data.

BACKGROUND: National mortality statistics are based on a single underlying cause of death. This practice does not adequately represent the impact of the range of conditions experienced in an ageing population in which multimorbidity is common. METHODS: We propose a new method for weighting the percentages of deaths attributed to different causes that takes account of the patterns of associations among underlying and contributing causes of death. It is driven by the data and unlike previously proposed methods does not rely on arbitrary choices of weights which can over-emphasise the contribution of some causes of death. The method is illustrated using Australian mortality data for people aged 60 years or more. RESULTS: Compared to the usual method based only on the underlying cause of death the new method attributes higher percentages of deaths to conditions like diabetes and dementia that are frequently mentioned as contributing causes of death, rather than underlying causes, and lower percentages to conditions to which they are closely related such as ischaemic heart disease and cerebrovascular disease. For some causes, notably cancers, which are usually recorded as underlying causes with few if any contributing causes the new method produces similar percentages to the usual method. These different patterns among groups of related conditions are not apparent if arbitrary weights are used. CONCLUSION: The new method could be used by national statistical agencies to produce additional mortality tables to complement the current tables based only on underlying causes of death.

Is there a link between infertility, miscarriage, stillbirth, and premature or early menopause? Results from pooled analyses of 9 cohort studies.

BACKGROUND: Some reproductive factors (such as age at menarche and parity) have been shown to be associated with age at natural menopause, but there has been little quantitative analysis of the association between infertility, miscarriage, stillbirth, and premature (<40 years) or early menopause (40-44 years). In addition, it has been unknown whether the association differs between Asian and non-Asian women, although the age at natural menopause is younger among Asian women. OBJECTIVE: This study aimed to investigate the association of infertility, miscarriage, and stillbirth with age at natural menopause, and whether the association differed by race (Asian and non-Asian). STUDY DESIGN: This was a pooled individual participant data analysis from 9 observational studies contributing to the InterLACE consortium. Naturally postmenopausal women with data on at least 1 of the reproductive factors (ie, infertility, miscarriage, and stillbirth), age at menopause, and confounders (ie, race, education level, age at menarche, body mass index, and smoking status) were included. A multinomial logistic regression model was used to estimate relative risk ratios and 95% confidence intervals for the association of infertility, miscarriage, and stillbirth with premature or early menopause, adjusting for confounders. Between-study difference and within-study correlation were taken into account by including study as a fixed effect and indicating study as a cluster variable. We also examined the association with number of miscarriages (0, 1, 2, ≥3) and stillbirths (0, 1, ≥2), and tested whether the strength of association differed between Asian and non-Asian women. RESULTS: A total of 303,594 postmenopausal women were included. Their median age at natural menopause was 50.0 years (interquartile range, 47.0-52.0). The percentages of women with premature and early menopause were 2.1% and 8.4%, respectively. The relative risk ratios (95% confidence intervals) of premature and early menopause were 2.72 (1.77-4.17) and 1.42 (1.15-1.74) for women with infertility; 1.31 (1.08-1.59) and 1.37 (1.14-1.65) for women with recurrent miscarriages; and 1.54 (1.52-1.56) and 1.39 (1.35-1.43) for women with recurrent stillbirths. Asian women with infertility, recurrent miscarriages (≥3), or recurrent stillbirths (≥2) had higher risk of premature and early menopause compared with non-Asian women with the same reproductive history. CONCLUSION: Histories of infertility and recurrent miscarriages and stillbirths were associated with higher risk of premature and early menopause, and the associations differed by race, with stronger associations for Asian women with such reproductive history.

Hypertension medication from guidelines to practice: A cohort study in western Iran.

PURPOSE: Hypertension (HTN) is one of the most common risk factors for non-communicable chronic diseases. The aim of the current study is to evaluate the prescribing patterns of antihypertensive medications in Kermanshah Province, west of Iran. METHODS: The Ravansar Non-Communicable Diseases (RaNCD) cohort study is the first Kurdish community-based study; subjects' age ranged from 35 to 65 years. In order to examine the use of medications to control blood pressure, participants were asked to bring all prescribed medications to the study center. Treatments were compared with 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) Guidelines for the management of arterial HTN. RESULTS: From a total of 10 040 participants in RaNCD cohort, 1575 (15.7%) individuals were hypertensive, of whom, 1271 (80.7%) people were aware of their condition. From 1153 (73.20%) people under treatment, 840 (72.8%) had their HTN properly controlled. The most common medications used to treat HTN were losartan (27.5%), metoprolol (14.3%), and captopril (11.9%). Regardless of type of treatment, 49.3% of all patients have received the medication for l 6 ≥ years. The most commonly used drugs were ß-blockers and angiotension receptor blockers as 620 (31.0%) and 612 (30.6%), respectively. Multivariable analysis showed that female gender, those receive ≥3 antihypertensive agents, and using preferred combinations were associated with a better blood pressure control. In addition, the probability of hypertension control was less likely with increasing duration of treatment (i.e >6 years) and in obese patients with ≥35 kg/m2 . CONCLUSIONS: Even though adherence to the international guidelines was acceptable, improvements can be made for better control of HTN. Therefore, it is imperative to educate healthcare professionals on improving their selection of antihypertensive medications and combination therapy for hypertensive patients.

Symptom patterns and health service use of women in early adulthood: a latent class analysis from the Australian Longitudinal Study on Women's Health.

BACKGROUND: Symptoms can be strong drivers for initiating interaction with the health system, especially when they are frequent, severe or impact on daily activities. Research on symptoms often use counts of symptoms as a proxy for symptom burden, however simple counts don't provide information on whether groups of symptoms are likely to occur together or whether such groups are associated with different types and levels of healthcare use. Women have a higher symptom burden than men; however studies of symptom patterns in young women are lacking. We aimed to characterise subgroups of women in early adulthood who experienced different symptom patterns and to compare women's use of different types of health care across the different symptom subgroups. METHODS: Survey and linked administrative data from 7 797 women aged 22-27 years in 2017 from the 1989-95 cohort of the Australian Longitudinal Study on Women's Health were analysed. A latent class analysis was conducted to identify subgroups of women based on the frequency of 16 symptom variables. To estimate the associations between the latent classes and health service use, we used the "Bolck, Croon and Hagenaars" (BCH) approach that takes account of classification error in the assignment of women to latent classes. RESULTS: Four latent classes were identified, characterised by 1) low prevalence of most symptoms (36.6%), 2) high prevalence of menstrual symptoms but low prevalence of mood symptoms (21.9%), 3) high prevalence of mood symptoms but low prevalence of menstrual symptoms, (26.2%), and high prevalence of many symptoms (15.3%). Compared to the other three classes, women in the high prevalence of many symptoms class were more likely to visit general practitioners and specialists, use more medications, and more likely to have had a hospital admission. CONCLUSIONS: Women in young adulthood experience substantially different symptom burdens. A sizeable proportion of women experience many co-occurring symptoms across both physical and psychological domains and this high symptom burden is associated with a high level of health service use. Further follow-up of the women in our study as they enter their late 20 s and early 30 s will allow us to examine the stability of the classes of symptoms and their associations with general health and health service use. Similar studies in other populations are needed to assess the generalisability of the findings.

Associations of socioeconomic and health factors with dental non-attendance: A comparison of three cohorts of women.

OBJECTIVES: Most studies on factors influencing dental attendance are cross-sectional and focus on specific age groups. The associations between private ancillary health insurance, tobacco smoking, alcohol consumption and overweight/obesity with dental attendance were examined in three cohorts of Australian women of different ages using multiple waves of data over similar time periods. METHODS: Data from 10 233, 12 378 and 7892 women born in 1973-1978, 1946-1951 and 1921-1926 participating in the Australian Longitudinal Study on Women's Health were used. Poisson regression using generalized estimating equations was used to investigate factors associated with self-report of not visiting the dentist in the 12 months before completing each wave. RESULTS: The role of dental non-attendance was higher in women without insurance (versus those with insurance) in all cohorts with adjusted rate ratios (RR) of 1.52 95% CI 1.48-1.57, RR 1.45 95% CI 1.41-1.49 and RR 1.32 95% CI 1.28-1.36 in the 1973-78, 1946-51 and 1921-26 cohorts respectively. Current smokers at any intensity (versus never smokers) had a higher risk of non-attendance and the risk was strongest for women in the 1946-51 cohort who smoked ≥20 cigarettes/day (RR 1.35 95% CI 1.30-1.41). Compared with low-risk drinkers, non-drinkers were more likely to be non-attenders, but only in the two older cohorts. Women who were overweight or obese (versus healthy weight) were more likely to be non-attenders in all cohorts, with the risk of non-attendance higher with increasing BMI. CONCLUSIONS: This study emphasizes the continued need to address socioeconomic inequities in access to dental care, along with strategies to overcome barriers for those who are obese or smoke. In this study, barriers to access existed for women of all ages, indicating that interventions need to be appropriate across age groups.

Cohort profile: a prospective Australian cohort study of women's reproductive characteristics and risk of chronic disease from menarche to premenopause (M-PreM).

PURPOSE: Previous studies have identified associations between individual reproductive factors and chronic disease risk among postmenopausal women. However, few have investigated the association of different markers of reproductive function, their interactions and risk factors of chronic disease among women approaching menopause. The Menarche-to-PreMenopause (M-PreM) Study aims to examine the relationship between reproductive factors across the reproductive lifespan and risk indicators for chronic disease among women in their early-to-mid-40s. The purpose of this cohort profile paper is to describe the rationale, study design and participant characteristics of the M-PreM Study. PARTICIPANTS: Women born in 1973-1978 who participated in the Australian Longitudinal Study on Women's Health (ALSWH) were invited to undertake a clinical or self-administered assessment. A total of 1278 women were recruited from June 2019 to June 2021. FINDINGS TO DATE: The study measures included functional, cognitive and cardiometabolic tests, anthropometry, spirometry, respiratory health questionnaires, physical activity, sleep patterns, sex hormones, and cardiovascular and metabolic markers; whereas blood and saliva samples were used for the analysis of genetic variants of genes associated with reproductive characteristics and chronic disease. The mean age of the clinic and self-assessed participants was 44.6 and 45.3 years, respectively. The menopausal status of participants was similar between the two arms of the study: 38%-41% premenopausal, 20% perimenopausal, and 36% took oral contraception or hormone replacement therapy. Approximately 80% of women had at least one child and participants reported experiencing pregnancy complications: preterm birth (8%-13% of pregnancies), gestational diabetes (10%) and gestational hypertension (10%-15%). FUTURE PLANS: The biomedical data collected in the M-PreM Study will be linked to existing ALSWH survey data on sociodemographic factors, health behaviour, reproductive function, and early life factors collected over the past 20 years and health administrative data. The association between reproductive factors and risk indicators of chronic disease will be analysed.

The association between childhood sexual abuse and historical intimate partner violence with body mass index and diabetes: Evidence from the Australian Longitudinal Study on Women's Health.

The purpose of this study was to investigate the associations of childhood sexual abuse and historical intimate partner violence with body mass index and diabetes among mid-age women. Data from 5782 participants in the 1946-51 cohort of the Australian Longitudinal Study on Women's Health were used. The association of abuse reported to have occurred before 1996 with body mass index and incident diabetes during 20 years of follow-up were examined using longitudinal logistic regression. Women who experienced childhood sexual abuse only, historical intimate partner violence only, or both forms of abuse had higher risk of obesity compared to women who did not experience either form of abuse. The associations between experiencing childhood sexual abuse only, historical intimate partner violence only, or both forms of abuse and incident diabetes (adjusted odds ratios, AOR = 1.28, 95%CI = 1.00, 1.65, AOR = 1.27 (1.02, 1.58) and AOR = 1.74 (1.27, 2.38) respectively) were attenuated by adding body mass index and other variables in the model (AOR = 1.16, 95%CI = 0.90, AOR = 1.49, 1.17 (0.94, 1.46) and AOR = 1.41 (1.03, 1.95) respectively) compared with women who did not experience abuse. The clinical implication is that awareness of a woman's early life experience of abuse may provide insight into managing her weight and risk of diabetes.

History of pre-pregnancy maternal symptoms of binge eating and childhood behavioral problems in girls and boys.

OBJECTIVE: To explore whether children of mothers with pre-pregnancy binge eating (BE) symptoms have more behavioral difficulties compared with those without and whether associations are moderated by ED symptoms and other maternal health and social factors measured during childhood. METHOD: Pre-pregnancy BE symptoms were collected by the Australian Longitudinal Study on Women's Health at Survey 1 (in 1996) and/or at Survey 2 (in 2000) using questions mapped to DSM BE criterion 1. In 2016/7, 2180 women from the 1973-78 cohort provided data on externalizing and internalizing behavior, measured by Strengths and Difficulties Questionnaire, on 4054 of their children (2-12 years) in the Mothers and their Children's Health study. Covariates were markers of other ED symptoms, sociodemographic, social support, and mental health factors collected proximally to the child outcomes. Hierarchical multivariable regression models, using generalized estimating equations accounting for clustering of children within mothers, were used. RESULTS: Pre-pregnancy BE symptoms were associated with child behavior, with associations only moderated after adjustment for proximal markers of ED (girls internalizing behavior, b (95%CI) .30 (-.02, .61); boys externalizing behavior .34 (-.04, .73)) or social support (girls externalizing behavior 0.26 (-.08, .61)). Pre-pregnancy BE symptoms were not associated with boys internalizing behavior (-.27 (-.02, 0.57)). DISCUSSION: Studies with repeated ED measures should test hypotheses that these associations vary by timing of ED measurement. Identification of young women at risk of BE symptoms pre-pregnancy, as well as when children are older, may enable health services, treatment programs, and supports to minimize longer term effects on children. PUBLIC SIGNIFICANCE STATEMENT: A history of binge eating symptoms up to 10 years pre-pregnancy in mothers is associated with behavior problems in their girls and boys at average age of 7. However, the association is moderated by behaviors of eating disorders and social support in the mothers during childhood. Identification of ED symptoms prior to pregnancy, and then after childbirth, might enable health services to intervene to maximize child and mother outcomes.

Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: cohort study of UK Biobank participants.

STUDY QUESTION: What is the association between menopausal hormone therapy (MHT) and cause-specific mortality? SUMMARY ANSWER: Self-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes. WHAT IS KNOWN ALREADY: Evidence from the Women's Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality. STUDY DESIGN, SIZE, DURATION: Cohort study (the UK Biobank), 178 379 women, recruited in 2006-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Postmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50-52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45-49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6-20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74). LIMITATIONS, REASONS FOR CAUTION: Self-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT. WIDER IMPLICATIONS OF THE FINDINGS: The current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation. STUDY FUNDING/COMPETING INTEREST(S): This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.