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.

Recommended measurement instruments for genitourinary symptoms associated with menopause: the COMMA (Core outcomes in menopause) consortium.

OBJECTIVE: The aim of the study is to identify appropriate definitions and patient-reported outcome measures (PROMs) for each of the eight core outcomes previously selected for genitourinary symptoms associated with menopause: pain with sex, vulvovaginal dryness, vulvovaginal discomfort or irritation, discomfort or pain when urinating, change in most bothersome symptom, distress, bother or interference of genitourinary symptoms, satisfaction with treatment, and side effects. METHODS: We conducted a systematic review to identify possible definitions and PROMs, including their measurement properties. Identified definitions and relevant PROMs with acceptable measurement properties were entered into an international consensus process involving 28 participants from 10 countries to achieve final recommendations for each core outcome. RESULTS: A total of 87 publications reporting on 34 PROMs were identified from 21,207 publications screened. Of these 34 PROMs, 29 were not considered to sufficiently map onto the core outcomes, and 26 of these also had insufficient measurement properties. Therefore, only five PROMs corresponding to two core outcomes were considered for recommendation. We recommend the PROMIS Scale v2.0 - Sexual Function and Satisfaction: Vaginal Discomfort with Sexual Activity to measure the outcome of "pain with sexual activity" and the Day-to-Day Impact of Vaginal Aging (DIVA) Questionnaire to measure "distress, bother or interference" from genitourinary symptoms. Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events in study participants, which is a requirement of Good Clinical Practice. CONCLUSIONS: Suitable PROMs and definitions were identified to measure three of eight core outcomes. Because of the lack of existing measures, which align with the core outcomes and have evidence of high-quality measurement properties, future work will focus on developing or validating PROMs for the remaining five core outcomes.

Associations between factors in childhood and young adulthood and childlessness among women in their 40s: A national prospective cohort study.

BACKGROUND: While the risk factors for infertility are well-established, research on factors associated with voluntary childlessness is limited and mainly focused on adulthood factors. Thus, we examined the associations between factors in childhood and young adulthood and different types of childlessness. METHODS: The analysis included 4653 women from the Australian Longitudinal Study on Women's Health from 1996 to 2021. Childlessness was categorised as: voluntary, due to infertility issues, or due to other reasons. The associations between factors in childhood and young adulthood and childlessness were assessed using multinomial logistic regression models. RESULTS: In their 40s, 4.8 % of women were voluntarily childless, 6.7 % were childless due to infertility issues, and 7.8 % were childless due to other reasons. Regardless of types of childlessness, being childless was associated with poorer self-rated health during childhood and having been unpartnered and obese in young adulthood. Ex-smokers in young adulthood had lower odds of childlessness. Childhood physical abuse was associated with childlessness due to infertility issues and other reasons. Voluntary childlessness and childlessness due to infertility issues were associated with having identified as non-exclusively heterosexual in early adulthood. Lower social support in early adulthood was associated with voluntary childlessness and childlessness due to other reasons. LIMITATIONS: The direction of the associations could not be determined and using self-reported data may introduce recall bias. CONCLUSIONS: Factors in childhood and young adulthood were associated with different types of childlessness, highlighting the importance of adopting a life course perspective when studying childlessness.

Recommended measurement instruments for menopausal vasomotor symptoms: the COMMA (Core Outcomes in Menopause) consortium.

OBJECTIVE: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects. METHODS: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome. RESULTS: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice. CONCLUSIONS: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.

Risk of Iron Deficiency in Women With Endometriosis: A Population-Based Prospective Cohort Study.

BACKGROUND: Endometriosis may be linked to the risk of iron deficiency through chronic systemic inflammation or heavy menstrual bleeding. No longitudinal studies, however, have examined the relationship between endometriosis and the risk of iron deficiency. METHODS: This study included 3,294 participants born from 1973 to 1978 and followed as part of the Australian Longitudinal Study on Women's Health from 2000 to 2018. Participants with endometriosis were identified using self-reported longitudinal surveys linked to administrative health records. During each survey, participants were also asked to report the diagnosis of iron deficiency, and we validated diagnoses using an administrative health database. Generalized estimating equations for binary responses with an autoregressive correlation matrix were used to examine the association between endometriosis and the risk of iron deficiency over the seven time points. FINDINGS: We found that women with endometriosis had a significantly higher risk of iron deficiency than those without endometriosis after adjusting for sociodemographic, lifestyle, reproductive, and nutrition factors (adjusted odds ratio [aOR] = 1.46; 95% confidence interval [CI] [1.29, 1.66]; p < .0001). Women with a surgically confirmed diagnosis and those with clinically suspected endometriosis had a higher risk of iron deficiency (aOR = 1.38; 95% CI [1.17, 1.64] and aOR = 1.53; 95% CI [1.30, 1.81]), respectively. These associations, however, were slightly attenuated (by 8%) when adjusted for the presence of heavy menstrual bleeding. CONCLUSIONS: Women with endometriosis are at a higher risk of developing iron deficiency than those without endometriosis. The findings suggest that iron deficiency should be concomitantly addressed during initial diagnosis and successive management of endometriosis.

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.

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.

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol.

INTRODUCTION: Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management. METHODS AND ANALYSIS: The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used. ETHICS AND DISSEMINATION: Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings. TRIAL REGISTRATION NUMBER: NCT05972785.

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.

Sustained Hypothetical Interventions on Midlife Alcohol Consumption in Relation to All-Cause and Cancer Mortality: The Australian Longitudinal Study on Women's Health.

No randomized controlled trial has evaluated the effect of long-term alcohol interventions on mortality. Results reported in existing observational studies may be subject to selection bias and time-varying confounding. Using data from the Australian Longitudinal Study on Women's Health 1946-1951 birth cohort, collected regularly from 1996-2016, we estimated all-cause and cancer mortality had women been assigned various alcohol interventions (in categories ranging from 0 to >30 g/day ethanol, or reduced to ≤20 g/day if higher) at baseline, and had they maintained these levels of consumption. The cumulative risks for all-cause and cancer mortality were 5.6% (10,118 women followed for 20 years) and 2.9% (18 years), respectively. For all-cause and cancer mortality, baseline ethanol up to 30 g/day showed lower risk and >30 g/day showed higher risk relative to abstention. Had women sustainedly followed the interventions, a similar relationship was observed for all-cause mortality. However, the negative association observed for intakes ≤30 g/day and positive association for intakes >30 g/day was not evident for cancer mortality. Our findings suggest that all-cause mortality could have been lower than observed if this cohort of women had consumed some alcohol (no more than 30 g/day) rather than no consumption, but cancer mortality might not.

Examination of Physical Activity, Organized Sport, and Sitting Time Among Women and Mothers From Culturally and Linguistically Diverse Backgrounds.

BACKGROUND: Little evidence is available from culturally and linguistically diverse (CALD) communities on the association between motherhood and physical activity (PA). This study aimed to examine independent and joint associations of cultural background and motherhood with meeting PA guidelines, participation in organized sports, and high sitting time (>8 h/d). METHODS: We used self-reported cross-sectional data from survey 8 of the 1973-1978 cohort of the Australian Longitudinal Study on Women's Health. PA was measured using the Active Australia Survey while organized sport and sitting time were measured using single items. CALD was defined as being born in a non-English speaking country or primarily speaking a non-English language at home. Multivariable-adjusted logistic regression analyses were used to examine independent and joint associations. RESULTS: Data from 5967 women (mean age 42.4 [SD 1.5] y, 6.9% CALD, 81.2% mothers) were analyzed. Women of CALD background had lower odds of meeting PA guidelines (odds ratio; 95% confidence interval: 0.80; 0.64-0.98) and participation in organized sports (0.68; 0.54-0.86), but no statistically significant association with sitting time (0.90; 0.72-1.14). Mothers had lower odds of meeting PA guidelines (0.75; 0.64-0.87) and high sitting time (0.42; 0.36-0.49). Compared with non-CALD women without children, mothers (irrespective of cultural background) were less likely to meet PA guidelines and have high sitting time. The association of "cultural background and motherhood" with organized sports participation was only significant for CALD mothers. CONCLUSIONS: Increased efforts and investments are needed to ensure that sports and other PA promotion interventions are culturally sensitive and engaging for CALD women and those with children.

Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium.

BACKGROUND AND AIMS: Physical inactivity, sedentary behaviour (SB), and inadequate sleep are key behavioural risk factors of cardiometabolic diseases. Each behaviour is mainly considered in isolation, despite clear behavioural and biological interdependencies. The aim of this study was to investigate associations of five-part movement compositions with adiposity and cardiometabolic biomarkers. METHODS: Cross-sectional data from six studies (n = 15 253 participants; five countries) from the Prospective Physical Activity, Sitting and Sleep consortium were analysed. Device-measured time spent in sleep, SB, standing, light-intensity physical activity (LIPA), and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included body mass index (BMI), waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, and glycated haemoglobin (HbA1c). Compositional linear regression examined associations between compositions and outcomes, including modelling time reallocation between behaviours. RESULTS: The average daily composition of the sample (age: 53.7 ± 9.7 years; 54.7% female) was 7.7 h sleeping, 10.4 h sedentary, 3.1 h standing, 1.5 h LIPA, and 1.3 h MVPA. A greater MVPA proportion and smaller SB proportion were associated with better outcomes. Reallocating time from SB, standing, LIPA, or sleep into MVPA resulted in better scores across all outcomes. For example, replacing 30 min of SB, sleep, standing, or LIPA with MVPA was associated with -0.63 (95% confidence interval -0.48, -0.79), -0.43 (-0.25, -0.59), -0.40 (-0.25, -0.56), and -0.15 (0.05, -0.34) kg/m2 lower BMI, respectively. Greater relative standing time was beneficial, whereas sleep had a detrimental association when replacing LIPA/MVPA and positive association when replacing SB. The minimal displacement of any behaviour into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day. CONCLUSIONS: Compositional data analyses revealed a distinct hierarchy of behaviours. Moderate-vigorous physical activity demonstrated the strongest, most time-efficient protective associations with cardiometabolic outcomes. Theoretical benefits from reallocating SB into sleep, standing, or LIPA required substantial changes in daily activity.

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.

Fertility treatment pathways and births for women with and without polycystic ovary syndrome-a retrospective population linked data study.

OBJECTIVE: To study the fertility treatment pathways used by women with and without polycystic ovary syndrome (PCOS) and which pathways were more likely to result in a birth. DESIGN: This retrospective national community-based cohort study used longitudinal self-report survey data (collected 1996-2022; aged 18-49 years) from women born in 1973-1978 who are participants in the Australian Longitudinal Study on Women's Health. The study also used linked administrative data on fertility treatments (1996-2021). PATIENTS: Of the 8,463 eligible women, 1,109 accessed fertility treatment and were included. EXPOSURE: Polycystic ovary syndrome diagnosis was self-reported. MAIN OUTCOME MEASURE: use of ovulation induction (OI), intrauterine insemination, and/or in vitro fertilization (IVF) was established through linked administrative data. Births were self-reported. RESULTS: One in 10 of the eligible participants had PCOS (783/7,987, 10%) and 1 in 4 of the women who used fertility treatment had PCOS (274/1,109, 25%). Women with PCOS were 3 years younger on average at first fertility treatment (M = 31.4 years, SD = 4.18) than women without PCOS (M = 34.2 years, SD = 4.56). Seven treatment pathways were identified and use differed by PCOS status. Women with PCOS were more likely to start with OI (71%; odds ratio [OR] 4.20, 95% confidence interval [CI]: 2.91, 6.07) than women without PCOS (36%). Of the women with PCOS who started with OI, 46% required additional types of treatment. More women without PCOS ended up in IVF (72% vs. 51%). Overall, 63% (701/1,109) had an attributed birth, and in adjusted regressions births did not vary by last type of treatment (IVF: 67%, reference; intrauterine insemination: 67%, OR 0.94 95% CI: 0.56, 1.58; OI: 61%, OR 0.71, 95% CI: 0.52, 0.98), or by PCOS status (OR 1.27, 95% CI: 0.91, 1.77). By age, 74% of women under 35 years (471/639) and 49% of women 35 years or older had a birth. CONCLUSION: More women with PCOS used fertility treatment but births were equivalent to women without PCOS. Most women followed clinical recommendations. Births did not differ between pathways, so there was no disadvantage in starting with less invasive treatments (although there may be financial or emotional disadvantages).

Evidence of shared genetic factors in the etiology of gastrointestinal disorders and endometriosis and clinical implications for disease management.

In clinical practice, the co-existence of endometriosis and gastrointestinal symptoms is often observed. Using large-scale datasets, we report a genetic correlation between endometriosis and irritable bowel syndrome (IBS), peptic ulcer disease (PUD), gastro-esophageal reflux disease (GORD), and a combined GORD/PUD medicated (GPM) phenotype. Mendelian randomization analyses support a causal relationship between genetic predisposition to endometriosis and IBS and GPM. Identification of shared risk loci highlights biological pathways that may contribute to the pathogenesis of both diseases, including estrogen regulation and inflammation, and potential therapeutic drug targets (CCKBR; PDE4B). Higher use of IBS, GORD, and PUD medications in women with endometriosis and higher use of hormone therapies in women with IBS, GORD, and PUD, support the co-occurrence of these conditions and highlight the potential for drug repositioning and drug contraindications. Our results provide evidence of shared disease etiology and have important clinical implications for diagnostic and treatment decisions for both diseases.