An empowerment model for managing menopause.

Menopause eventually happens to all people with typically functioning ovaries, and almost one billion women worldwide are postmenopausal. Although the biology of typical menopause is ubiquitous, the experience varies substantially. Factors contributing to the experience include not only individual factors, such as the nature and severity of symptoms, but also psychological, social, and contextual considerations, many of which are modifiable. In this first paper in the Lancet Series on menopause, we argue for a new approach that goes beyond the treatment of specific symptoms, to encompass a broad model to support women transitioning this life stage, using the model of empowerment. WHO defines empowerment as an active process of gaining knowledge, confidence, and self-determination to self-manage health and make informed decisions about care. Rather than focusing on menopause as an endocrine deficiency, we propose an empowerment model that recognises factors modifying the experience, in which the patient is an expert in their own condition and the health-care worker supports the patient to become an equal and active partner in managing their own care.

Optimising health after early menopause.

The typical age at menopause is 50-51 years in high-income countries. However, early menopause is common, with around 8% of women in high-income countries and 12% of women globally experiencing menopause between the ages of 40 years and 44 years. Menopause before age 40 years (premature ovarian insufficiency) affects an additional 2-4% of women. Both early menopause and premature ovarian insufficiency can herald an increased risk of chronic disease, including osteoporosis and cardiovascular disease. People who enter menopause at younger ages might also experience distress and feel less supported than those who reach menopause at the average age. Clinical practice guidelines are available for the diagnosis and management of premature ovarian insufficiency, but there is a gap in clinical guidance for early menopause. We argue that instead of distinct age thresholds being applied, early menopause should be seen on a spectrum between premature ovarian insufficiency and menopause at the average age. This Series paper presents evidence for the short-term and long-term consequences of early menopause. We offer a practical framework for clinicians to guide diagnosis and management of early menopause, which considers the nature and severity of symptoms, age and medical history, and the individual's wishes and priorities to optimise their quality of life and short-term and long-term health. We conclude with recommendations for future research to address key gaps in the current evidence.

Promoting good mental health over the menopause transition.

The potential risk for mental health conditions over the menopause transition shapes women's expectations and informs putative physiological mechanisms regulating women's mental health. We review evidence from prospective studies reporting on associations between mental health conditions and the menopause transition. Major depressive disorder and the more prevalent subthreshold depressive symptoms are the most common conditions studied. We reviewed 12 prospective studies reporting depressive symptoms, major depressive disorder, or both over the menopause transition and found no compelling evidence for a universal increased risk for either condition. However, specific subgroups of participants, primarily defined by menopause-related risk factors (ie, vasomotor symptoms that are severe or disturb sleep, a long duration of the transition, or reproductive hormone dynamics) and psychosocial risk factors (eg, stressful life events), were vulnerable to depressive symptoms. The increased risk of major depressive disorder over the menopause transition appears predominantly in individuals with previous major depressive disorder. Greater focus on recognising risk factors in primary care is warranted. On the basis of scarce data, we found no compelling evidence that risk of anxiety, bipolar disorder, or psychosis is universally elevated over the menopause transition. Potential misattribution of psychological distress and psychiatric disorders to menopause could harm women by delaying accurate diagnosis and the initiation of effective psychotropic treatments, and by creating negative expectations for people approaching menopause. A paradigm shift is needed. We conclude with recommendations for the detection and treatment of depressive symptoms or major depressive disorder and strategies to promote good mental health over the menopause transition, while responsibly preparing and supporting those at risk.

Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose-response associations from the Prospective Physical Activity, Sitting and Sleep Consortium.

AIMS/HYPOTHESIS: The aim of this study was to examine the dose-response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. METHODS: We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. RESULTS: We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] -0.14 [-0.25, -0.02]) and 5 min/day stair climbing (-0.14 [-0.24, -0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose-response associations for any activity type or standing. There was an inverse dose-response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose-response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. CONCLUSIONS/INTERPRETATION: In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent CVD and medication use. Our findings on cardiometabolic health and durations of different activities of daily living and posture may guide future interventions involving lifestyle modification.

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.

The association between preconception cannabis use and gestational diabetes mellitus: The Preconception Period Analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.

BACKGROUND: The metabolic changes that ultimately lead to gestational diabetes mellitus (GDM) likely begin before pregnancy. Cannabis use might increase the risk of GDM by increasing appetite or promoting fat deposition and adipogenesis. OBJECTIVES: We aimed to assess the association between preconception cannabis use and GDM incidence. METHODS: We analysed individual-level data from eight prospective cohort studies. We identified the first, or index, pregnancy (lasting ≥20 weeks of gestation with GDM status) after cannabis use. In analyses of pooled individual-level data, we used logistic regression to estimate study-type-specific odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders using random effect meta-analysis to combine study-type-specific ORs and 95% CIs. Stratified analyses assessed potential effect modification by preconception tobacco use and pre-pregnancy body mass index (BMI). RESULTS: Of 17,880 participants with an index pregnancy, 1198 (6.7%) were diagnosed with GDM. Before the index pregnancy, 12.5% of participants used cannabis in the past year. Overall, there was no association between preconception cannabis use in the past year and GDM (OR 0.97, 95% CI 0.79, 1.18). Among participants who never used tobacco, however, those who used cannabis more than weekly had a higher risk of developing GDM than those who did not use cannabis in the past year (OR 2.65, 95% CI 1.15, 6.09). This association was not present among former or current tobacco users. Results were similar across all preconception BMI groups. CONCLUSIONS: In this pooled analysis of preconception cohort studies, preconception cannabis use was associated with a higher risk of developing GDM among individuals who never used tobacco but not among individuals who formerly or currently used tobacco. Future studies with more detailed measurements are needed to investigate the influence of preconception cannabis use on pregnancy complications.

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.

Large-Scale Data Harmonization Across Prospective Studies.

The Preconception Period Analysis of Risks and Exposures Influencing Health and Development (PrePARED) Consortium creates a novel resource for addressing preconception health by merging data from numerous cohort studies. In this paper, we describe our data harmonization methods and results. Individual-level data from 12 prospective studies were pooled. The crosswalk-cataloging-harmonization procedure was used. The index pregnancy was defined as the first postbaseline pregnancy lasting more than 20 weeks. We assessed heterogeneity across studies by comparing preconception characteristics in different types of studies. The pooled data set included 114,762 women, and 25,531 (22%) reported at least 1 pregnancy of more than 20 weeks' gestation during the study period. Babies from the index pregnancies were delivered between 1976 and 2021 (median, 2008), at a mean maternal age of 29.7 (standard deviation, 4.6) years. Before the index pregnancy, 60% of women were nulligravid, 58% had a college degree or more, and 37% were overweight or obese. Other harmonized variables included race/ethnicity, household income, substance use, chronic conditions, and perinatal outcomes. Participants from pregnancy-planning studies had more education and were healthier. The prevalence of preexisting medical conditions did not vary substantially based on whether studies relied on self-reported data. Use of harmonized data presents opportunities to study uncommon preconception risk factors and pregnancy-related events. This harmonization effort laid the groundwork for future analyses and additional data harmonization.

Is being childless associated with a woman's risk of overweight and obesity? Results from a national longitudinal study.

AIM: To examine the association between motherhood status (mothers, voluntarily childless, involuntarily childless) and overweight and obesity over 22 years. METHODS: A total of 4092 women aged 18-23 years were followed from 1996 to 2018. Motherhood status was defined by women's reports on their fertility, attempts to conceive, use of in vitro fertilisation and fertility hormones, and number of biological children. Associations between motherhood status and overweight and obesity were examined using generalised estimating equations models, adjusting for socio-demographic characteristics, lifestyle factors, depressive symptoms, early life factors, and polycystic ovary syndrome (PCOS). RESULTS: At age 40-45 years, 12% of women were voluntarily childless and 5% were involuntarily childless. The prevalence of overweight and obesity increased with age and women who were voluntarily or involuntarily childless had higher prevalence of obesity than mothers in all surveys. After adjusting for covariates, compared with mothers, women who were voluntarily childless had higher odds of being overweight (odds ratio [OR], 95% confidence interval [CI]: 1.29, 1.09-1.52) and obese (OR, 95% CI: 1.65, 1.29-2.12). Involuntary childlessness was not associated with being overweight (OR, 95% CI: 1.05, 0.82-1.33), and its association with obesity was attenuated after adjusting for PCOS in the final model (OR, 95% CI: 1.40, 0.99-1.98). CONCLUSIONS: Around one in nine Australian women remained voluntarily childless by their late reproductive years. On average, they had higher odds of being overweight and obese than mothers, suggesting that overweight and obesity prevention programs should consider tailoring their advice by motherhood status.

Associations between endometriosis and common symptoms: findings from the Australian Longitudinal Study on Women's Health.

BACKGROUND: Endometriosis has been linked to higher rates of a variety of symptoms; however, the findings from longitudinal studies are scarce and inconsistent. OBJECTIVE: This study aimed to examine the association between endometriosis and common symptoms in a prospective cohort study. STUDY DESIGN: This study included 7606 women born from 1973 to 1978 using data from the Australian Longitudinal Study on Women's Health that were collected every 3 years from 2009 to 2018. We identified women with endometriosis based on self-reported incidence from each survey and linked administrative health data. At each survey, women also completed a checklist on the presence of 24 symptoms. Generalized estimating equations for multinomial responses were used for analyses. RESULTS: Women with endometriosis had significantly more menstrual symptoms than those without endometriosis with an adjusted odds ratio (95% confidence interval) of 3.61 (3.11-4.19) for severe period pain, 2.40 (2.10-2.74) for heavy menstrual bleeding, 1.76 (1.52-2.03) for irregular bleeding, and 1.52 (1.32-1.76) for premenstrual tension. They also had higher odds of mental health problems with adjusted odds ratios of 1.67 (1.39-2.01) for depression and 1.59 (1.24-2.03) for anxiety and higher odds of allergies and nonspecific symptoms with adjusted odds of 1.62 (1.40-1.89) for allergies or hay fever or sinusitis, 1.79 (1.56-2.05) for severe tiredness, 1.56 (1.35-1.81) for sleep difficulty, and 1.77 (1.37-2.18) for palpitations. There was also a strong association with other forms of pain with an adjusted odds ratio of 1.76 (1.53-2.04) for backpain, 1.50 (1.29-1.74) for headaches or migraines, and 1.65 (1.41-1.93) for stiff or painful joints. Women with endometriosis also had increased odds of developing bowel and urinary symptoms with an adjusted odds ratio (95% confidence interval) of 1.67 (1.35-2.08) for constipation, 1.46 (1.12-1.90) for hemorrhoids or piles, 1.25 (1.03-1.52) for indigestion or heartburn, 2.80 (1.71-4.58) for urine burn or stings, and 1.37 (1.03-1.82) for vaginal discharge or irritation. The association between each symptom and endometriosis was similar whether endometriosis was surgically confirmed or clinically suspected. No association was found between endometriosis and the risk for skin problems, leaking urine, or breathing difficulty. CONCLUSION: This study suggests that women with endometriosis are more likely to report not only menstrual symptoms but are also at an increased risk for mental health problems, other pain symptoms, bowel and urinary symptoms, and nonspecific symptoms, such as severe tiredness and difficulty sleeping.

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.

Associations of changes in physical activity and diet with incident obesity and changes in adiposity: Longitudinal findings from the UK Biobank.

We examined the association of changes in physical activity and diet with obesity development and changes in body fat percentage, body mass index, and waist circumference. 31,344 adults without obesity at baseline (age = 56.0 ± 7.5 years; female = 49.1%) from the UK Biobank were included. Physical activity was categorised based on public health guidelines as: inactive; insufficient; and sufficient. Diet category was assigned based on an established composited score that included consumption of fruits, vegetables, fish, red meat (unprocessed), and processed meat. Diet was categorised as: poor; reasonable; and good. Physical activity and diet changes were categorised based on changes in category: worsened; stable; increased (physical activity)/improved (diet). During a mean follow up of 6.8 (SD = ±2.3) years, 1354 (4.3%) participants developed obesity. Compared to stable physical activity-diet, increasing physical activity was associated with the lowest obesity odds, across diet changes (e.g., OR [95%CI]: diet worsened (0.89 [0.69, 1.15]); diet improved (0.65 [0.48, 0.89])). Increasing physical activity with improved diet was associated with the largest difference in body fat percentage (ß:-0.62 [-0.82, -0.41]), body mass index (-0.37 [-0.47, -0.28]), and waist circumference (-1.21 [-1.63, -0.79]). Excluding adults with a history of smoking, or major illness, lowered obesity odds among participants with increased physical activity by an additional 11%-21%. In those who decreased physical activity obesity was attenuated when combined with diet improvement. Improvements in physical activity or diet mutually attenuated the deleterious associations of the other behaviour's deterioration. In most analyses, increases in physical activity conferred consistent positive associations against the development of obesity, across dietary change groups.

Excess healthcare costs of psychological distress in young women: Evidence from linked national Medicare claims data.

The prevalence of mental health disorders in young adults is increasing, yet there is limited empirical evidence on its economic consequences. We contribute to the literature by estimating the healthcare costs of psychological distress using panel data of young women (aged 18-23 years with a 5-year follow-up) from the Australian Longitudinal Study on Women's Health and linked administrative data from Medicare Australia. Our empirical strategy is based on the classical two-part model of healthcare costs with individual specific fixed-effects. We complement our analysis with a test for selection on unobservables to address potential concerns of endogeneity. We find that young women with psychological distress have 15% higher annual healthcare costs (excluding hospital costs) than women with no psychological distress. A large proportion of these costs is driven by the use of antidepressants and the services of psychiatrists and psychologists. We further find that women with psychological distress have higher out-of-pocket costs on these mental health related services compared to non-mental health specific services. Additionally, we show that the effect of psychological distress on healthcare costs is highest during the first 6 months of onset, which gradually decreases afterwards. The findings justify the importance of policy initiatives towards early prevention and treatment of psychological distress, especially among young women.

Do mothers or females without children have better health-related quality of life across their reproductive years?

PURPOSE: To compare health-related quality of life (HRQoL) between mothers and females who were voluntarily or involuntarily childless, across their reproductive years. METHODS: 4100 females born in 1973-78 from the Australian Longitudinal Study on Women's Health were followed for 22 years. Motherhood status was defined by females' reports in Survey 8 (2018, 40-45 years) on their fertility, attempts to conceive, use of in vitro fertilization and fertility hormones, and number of children. HRQoL was assessed in each survey using the 36-Item Short Form Survey (SF-36). Linear mixed models were used to assess the associations between motherhood status and HRQoL. RESULTS: Over 22 years, compared with females who were voluntarily childless, mothers on average had better HRQoL (shown by scores 1.5 to 3.4 points higher on five of the eight SF-36 subscales), while females who were involuntarily childless scored 2.2 to 3.0 points lower on three of eight SF-36 subscales. Compared with females who were voluntarily childless, teen mothers (age at first birth < 20 years) scored lower on role limitations due to physical problems subscale (b = -5.5, 95% CI: -9.3, -1.6), while females with either two, or three or more children scored 1.6 to 4.8 points higher on seven of eight SF-36 subscales. CONCLUSIONS: Females who were childless had poorer HRQoL than mothers. Further research is needed to understand the underlying mechanisms, which could inform policymakers on how to reduce the health disparities and improve long-term health outcomes for females.

Symptoms of sleep problems and adherence to dietary guidelines in older women: evidence from the Australian Longitudinal Study on Women's Health.

OBJECTIVE: This study examined adherence to dietary guidelines and symptoms of sleep problems (e.g. taking a long time to fall sleep or waking up early) and their associations in a sample of older Australian women (68-73 years of age). DESIGN: This was a population-based cross-sectional study. Adherence to the dietary guidelines was measured using a validated FFQ and reported as a diet quality score. Symptoms of sleep problems were measured using five questions and a total score was derived. Multivariate linear regression was used to investigate the association between these outcomes, adjusted for the potential confounding influence of demographic (i.e. age and marital status) and lifestyle (i.e. physical activity, stress, alcohol intake, sleep medication use) variables. SETTING: Respondents from the 1946-1951 cohort of the Australian Longitudinal Study on Women's Health who completed Survey 9 were included. PARTICIPANTS: Data from n 7956 older women (mean age ± sd: 70·8 ± 1·5) were included. RESULTS: 70·2 % reported having at least one symptom and 20·5 % had between 3 and 5 symptoms of sleep problems (mean score ± sd: 1·4 ± 1·4, range 0-5). Adherence to dietary guidelines was poor with an average diet quality score of 56·9 ± 10·7 (range 0-100). Better adherence to dietary guidelines was associated with fewer sleep problem symptoms (ß: -0·065, 95 % CI: -0·012, -0·005) and remained significant after adjusting for confounding influences. CONCLUSIONS: These findings support the evidence that adherence to dietary guidelines is associated with symptoms of sleep problems in older women.

Association between device-measured stepping behaviors and cardiometabolic health markers in middle-aged women: The Australian Longitudinal Study on Women's Health.

The associations between different types and contexts of stepping behaviors and cardiometabolic (CM) health markers are unclear. This study aimed to examine the associations of daily total, walking, stair, incidental and purposeful steps with cardiometabolic risk. A total of 943 women (mean age ± SD = 44.1 ± 1.6 years) from the Australian Longitudinal Study on Women's Health (ALSWH) were included in this cross-sectional study. Daily total, walking, stair, incidental, and purposeful steps were measured using thigh-worn accelerometry. Outcomes comprised of CM markers of adiposity, blood pressure, resting heart rate, lipids, glycaemia, and the composite CM score. We used generalized linear modeling and multiple linear regression to assess the associations. We observed that all stepping behaviors were beneficial to CM health, for example, compared to the lowest quartile (Q1), the change of the composite CM score across low to high quartile of purposeful steps was -0.12 (Q2, 95% CI: -0.41, 0.17), -0.16 (Q3, -0.46, 0.14), and -0.36 (Q4, -0.66, -0.05). Stair steps showed linear associations with blood pressure and adiposity biomarkers, for example, the change of quartile of waist circumference was -1.45 cm (Q2, -4.35, 1.44), -3.56 cm (Q3, -6.52, -0.60), and -7.08 cm (Q4, -10.31, -3.86). Peak 30-min walking intensity showed independent association with adiposity biomarkers (p linear < 0.001 and p = 0.002 for waist circumference and BMI, respectively). Our study showed that all stepping forms were beneficial to CM health. Higher stair steps and peak 30-min walking cadence were associated with a steep decline of adiposity biomarkers. Purposeful steps showed more consistent associations with CM biomarkers than incidental steps.

Maternal circulating leptin, tumor necrosis factor-alpha, and interleukine-6 in association with gestational diabetes mellitus: a systematic review and meta-analysis.

Background: Over the last decade, an emerging role of novel cytokines in the pathogenesis of gestational diabetes mellitus (GDM) has been proposed. The present study was implemented to provide a more accurate estimate of the effect size of the association between leptin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and the risk of GDM.Methods: Online databases were looked up to January 2023 using the search string: (leptin OR TNF-α OR IL-6) AND "gestational diabetes." Observational studies investigating the association of selected cytokines and GDM risk were included. Odds ratios and their 95% confidence intervals (CIs) were extracted and random-effects models were used to estimate the pooled effect.Results: Twenty-four studies were included in the meta-analysis. A significant association was found between higher circulating leptin and the risk of GDM and the pooled estimate was 1.16 (95%CI: 1.07, 1.27). Higher circulating levels of IL-6 and TNF-α were associated with increased risk of GDM, and the pooled estimates were 1.35 (95%CI: 1.05, 1.73) and 1.28 (95%CI: 1.01, 1.62), respectively.Conclusions: The studied cytokines could be implicated in the GDM pathogenesis and used as potential biomarkers for assessing the GDM risk. Additional longitudinal studies with large sample sizes are needed for a further evaluation of these findings.

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.

Infertility, Miscarriage, Stillbirth, and the Risk of Stroke Among Women: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Stroke is one of the leading causes of mortality, and women are impacted more from stroke than men in terms of their absolute number and in having worse outcomes. A growing number of studies have explored the association between pregnancy complications, pregnancy outcomes, and stroke. Limited studies, however, have investigated links involving infertility, miscarriage, and stillbirth, which could plausibly be associated via a background of endocrine conditions, endothelial dysfunction, and chronic systematic inflammation. This review aims to summarize current evidence and provide up-to-date information on the associations of infertility, miscarriage, and stillbirth, with stroke incidence. METHODS: A comprehensive literature search was conducted for cohort and case-control studies on associations between infertility, miscarriage, stillbirth, and stroke up to September 26, 2020. Seven databases were searched: PubMed, Embase, Cochrane, CINIHL, PsyclNFO, Wanfang, and CNKI. Random-effects models were used to estimate the pooled hazard ratios (HRs) and 95% CIs. RESULTS: Sixteen cohort studies and 2 case-control studies enrolling 7 808 521 women were included in this meta-analysis. Women who had experienced miscarriage or stillbirth were at higher risk of stroke (miscarriage: HR, 1.07 [95% CI, 1.00-1.14]; stillbirth: HR, 1.38 [95% CI, 1.11-1.71]) than other women. The HRs of stroke for each additional miscarriage and stillbirth were 1.13 (95% CI, 0.96-1.33) and 1.25 (95% CI, 1.06-1.49), respectively. In subgroup analysis, increased risk of stroke was associated with repeated miscarriages and stillbirths (miscarriage ≥3: HR, 1.42 [95% CI, 1.05-1.90]; stillbirth ≥2: HR, 1.14 [95% CI, 1.04-1.26]). Associations between infertility and stroke were inconsistent and inconclusive (HR, 1.07 [95% CI, 0.87-1.32]). CONCLUSIONS: Miscarriage and stillbirth are associated with increased risk of stroke among women, which could be used as a contributing risk factor to help identify women at higher risk of stroke.

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.