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The impact of the humanitarian crisis in Venezuela on care for noncommunicable diseases (NCDs) such as diabetes is unknown. This study aims to document health system performance for diabetes management in Venezuela during the humanitarian crisis. This longitudinal study on NCDs is nationally representative at baseline (2014-2017) and has follow-up (2018-2020) data on 35% of participants. Separate analyses of the baseline population with diabetes (n = 585) and the longitudinal population with diabetes (n = 210) were conducted. Baseline analyses constructed a weighted care continuum: all diabetes; diagnosed; treated; achieved glycaemic control; achieved blood pressure, cholesterol, and glycaemic control; and achieved aforementioned control plus non-smoking. Weighted multinomial regression models controlling for region were used to estimate the association between socio-demographic characteristics and care continuum stage. Longitudinal analyses constructed an unweighted care continuum: all diabetes; diagnosed; treated; and achieved glycaemic control. Unweighted multinomial regression models controlling for region were used to estimate the association between socio-demographic characteristics and changes in care continuum stage. Among 585 participants with diabetes at baseline, 71% were diagnosed, 51% were on treatment, and 32% had achieved glycaemic control. Among 210 participants with diabetes in the longitudinal population, 50 (24%) participants' diabetes management worsened, while 40 (19%) participants improved. Specifically, the proportion of those treated decreased (60% in 2014-2017 to 51% in 2018-2020), while the proportion of participants achieving glycaemic control did not change. Although treatment rates have declined substantially among people with diabetes in Venezuela, management changed less than expected during the crisis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Goodman-Palmer provides scientific consultations through Epidemiologic Research & Methods, LLC (ERM); none of her consulting through ERM is related to the topic of the current study. All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Context: The association between women's stress and pregnancy glucose levels remain unclear, specifically when considering the preconception period as a sensitive window of exposure., Objective: We investigated whether preconception perceived stress was associated with glucose levels during pregnancy among women attending a fertility center (2004-2019)., Methods: Before conception, women completed a psychological stress survey using the short version of the validated Perceived Stress Scale 4 (PSS-4), and blood glucose was measured using a 50-gram glucose load test during late pregnancy as a part of screening for gestational diabetes. Linear and log-binomial regression models were used to assess associations of total PSS-4 scores with mean glucose levels and abnormal glucose levels ( ≥ 140 mg/dL), adjusting for age, body mass index, race, smoking, education, physical activity, primary infertility diagnosis, number of babies, and mode of conception., Results: Psychological stress was positively associated with mean abnormal glucose levels. The adjusted marginal means (95% CI) of mean glucose levels for women in the first, second, and third tertiles of psychological stress were 115 (110, 119), 119 (115, 123), and 124 (119, 128), and mg/dL, respectively ( P for trend = .007). Also, women in the second and third tertiles of psychological stress had 4% and 13% higher probabilities of having abnormal glucose compared with women in the first tertile of psychological stress ( P trend = .01)., Conclusion: These results highlight the importance of considering preconception when evaluating the relationship between women's stress and pregnancy glucose levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Importance: Fertility status is a marker for future health, and infertility has been associated with risk for later cancer and diabetes, but associations with midlife cardiovascular health (CVH) in female individuals remain understudied., Objective: To evaluate the association of infertility history with CVH at midlife (approximately age 50 years) among parous individuals., Design, Setting, and Participants: Project Viva is a prospective cohort study of pregnant participants enrolled between 1999 and 2002 who delivered a singleton live birth in the greater Boston, Massachusetts, area. Infertility history was collected at a midlife visit between 2017 and 2021, approximately 18 years after enrollment. Data analysis was performed from January to June 2023., Exposures: The primary exposure was any lifetime history of infertility identified by self-report, medical record, diagnosis, or claims for infertility treatment., Main Outcomes and Measures: The American Heart Association's Life's Essential 8 (LE8) is a construct for ranking CVH that includes scores from 0 to 100 (higher scores denote better health status) in 4 behavioral (diet, physical activity, sleep, and smoking status) and 4 biomedical (body mass index, blood pressure, blood lipids, and glycemia) domains to form an overall assessment of CVH. Associations of a history of infertility (yes or no) with mean LE8 total, behavioral, biomedical, and blood biomarker (lipids and glycemia) scores were examined, adjusting for age at outcome (midlife visit), race and ethnicity, education, household income, age at menarche, and perceived body size at age 10 years., Results: Of 468 included participants (mean [SD] age at the midlife visit, 50.6 [5.3] years) with exposure and outcome data, 160 (34.2%) experienced any infertility. Mean (SD) LE8 scores were 76.3 (12.2) overall, 76.5 (13.4) for the behavioral domain, 76.0 (17.5) for the biomedical domain, and 78.9 (19.2) for the blood biomarkers subdomain. In adjusted models, the estimated overall LE8 score at midlife was 2.94 points lower (95% CI, -5.13 to -0.74 points), the biomedical score was 4.07 points lower (95% CI, -7.33 to -0.78 points), and the blood subdomain score was 5.98 points lower (95% CI, -9.71 to -2.26 points) among those with vs without history of infertility. The point estimate also was lower for the behavioral domain score (β = -1.81; 95% CI, -4.28 to 0.66), although the result was not statistically significant., Conclusions and Relevance: This cohort study of parous individuals found evidence for an association between a history of infertility and lower overall and biomedical CVH scores. Future study of enhanced cardiovascular preventive strategies among those who experience infertility is warranted.

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., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Modifiable factors, such as environmental exposures, can impact human fertility. The objective of this review is to summarize the potential effects of exposure to important endocrine-disrupting chemicals on male reproductive health. Most experimental and animal data demonstrate strong evidence for the negative effects of exposure to phenols, phthalates, pesticides, and perfluoroalkyl and polyfluoroalkyl substances on male reproductive health. Although evidence of negative associations in humans was overall strong for phthalates and pesticides, limited and inconclusive relationships were found for the other examined chemical biomarkers. Reasons for the discrepancies in results include but are not limited to, differences in study populations, exposure concentrations, number of samples collected, sample sizes, study design, and residual confounding. Additional studies are needed, particularly for newer phenols and perfluoroalkyl and polyfluoroalkyl substances, given the scarce literature on the topic and increasing exposures over time., Competing Interests: Declaration of interests L.M.A. has nothing to disclose. A.J.G. has nothing to disclose. J.D.M. has nothing to disclose. J.M.B. was financially compensated for serving as an expert witness for plaintiffs in litigation related to tobacco smoke exposures and received an honorarium for serving on an advisory board for Quest Diagnostics. J.M.B.’s institution was financially compensated for his services as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water; these funds were not paid to JMB directly. J.E.C. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Many women experience sleep problems during midlife. Associations of adverse lifetime experiences-more common among women-with sleep outcomes are understudied., Methods: We studied 476 women enrolled in Project Viva 1999-2002. At enrollment, participants reported any lifetime history of abuse and/or financial hardship. At midlife follow-up ∼20 years later, they reported a history of up to 10 adverse childhood experiences (ACEs); 7-day sleep quality (patient-reported outcomes measurement information system sleep disturbance and sleep-related impairment T-scores); and past month average sleep duration. We examined associations of adverse experiences with sleep outcomes, adjusted for childhood sociodemographic variables. We also explored mediation by current depression and anxiety symptoms, hot flash severity, general health, and body mass index., Results: ACEs were common: 301 women (63%) reported one or more. Each additional ACE was associated with higher midlife sleep disturbance (adjusted β = 0.65 points, 95% confidence interval [CI]: 0.27, 1.02) and sleep-related impairment (0.98, 95% CI: 0.54, 1.41) T-scores, and with sleep duration <6 hour/night (odds ratio 1.19, 95% CI: 1.00, 1.42), but not with continuous sleep duration (-2 minutes, 95% CI: -5, 1). Adverse experiences in adulthood were less consistently associated with sleep quality but were associated with sleep duration, for example, financial hardship during the index pregnancy was associated with 75 minutes (95% CI: -120, -29) shorter sleep duration 2 decades later. Associations of ACEs with sleep disturbance and sleep-related impairment were mediated by midlife depression anxiety and physical health but not by hot flash severity or body mass index., Conclusions: Adverse lifetime experiences have deleterious associations with sleep duration and quality in midlife women., Competing Interests: Declaration of conflicts of interest Dr. Klerman reports consulting income from the American Academy of Sleep Medicine Foundation, Circadian Therapeutics, National Sleep Foundation, and the Sleep Research Society Foundation; she has received travel support from the European Biological Rhythms Society and the Sleep Research Society; she is an unpaid member of the Scientific Advisory Board of Chronsulting; and her partner is founder, director, and chief scientific officer for Chronsulting. Dr. Joffe reports grants from NIH during the conduct of the study; grants from Pfizer, grants and personal fees from Merck, personal fees from Hello Therapeutics, personal fees from Bayer, outside the submitted work; and Spouse: Employee at Arsenal Biosciences; Equity at Merck Research Labs. Dr. Bertisch reports consulting fees from Idorsia Pharmaceuticals and ResMed. Other authors do not report any conflicts of interest., (Copyright © 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Endocrine disrupting chemicals (EDCs) can adversely affect human health and are ubiquitously found in everyday products. We examined temporal trends in urinary concentrations of EDCs and their replacements. Urinary concentrations of 11 environmental phenols, 15 phthalate metabolites, phthalate replacements such as two di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) metabolites, and triclocarban were quantified using isotope-dilution tandem mass spectrometry. This ecological study included 996 male and 819 female patients who were predominantly White/Caucasian (83 %) with an average age of 35 years and a BMI of 25.5 kg/m 2 seeking fertility treatment in Boston, MA, USA. Patients provided a total of 6483 urine samples (median = 2, range = 1-30 samples per patient) between 2000 and 2017. Over the study period, we observed significant decreases (% per year) in urinary concentrations of traditional phenols, parabens, and phthalates such as bisphenol A (β: -6.3, 95 % CI: -7.2, -5.4), benzophenone-3 (β: -6.5, 95 % CI: -1.1, -18.9), parabens ((β range:-5.4 to -14.2), triclosan (β: -18.8, 95 % CI: -24, -13.6), dichlorophenols (2.4-dichlorophenol β: -6.6, 95 % CI: -8.8, -4.3); 2,5-dichlorophenol β: -13.6, 95 % CI: -17, -10.3), di(2-ethylhexyl) phthalate metabolites (β range: -11.9 to -22.0), and other phthalate metabolites including mono-ethyl, mono-n-butyl, and mono-methyl phthalate (β range: -0.3 to -11.5). In contrast, we found significant increases in urinary concentrations of environmental phenol replacements including bisphenol S (β: 3.9, 95 % CI: 2.7, 7.6) and bisphenol F (β: 6, 95 % CI: 1.8, 10.3), DINCH metabolites (cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester [MHiNCH] β: 20, 95 % CI: 17.8, 22.2; monocarboxyisooctyl phthalate [MCOCH] β: 16.2, 95 % CI: 14, 18.4), and newer phthalate replacements such as mono-3-carboxypropyl phthalate, monobenzyl phthalate, mono-2-ethyl-5-carboxypentyl phthalate and di-isobutyl phthalate metabolites (β range = 5.3 to 45.1), over time. Urinary MHBP concentrations remained stable over the study period. While the majority of biomarkers measured declined over time, concentrations of several increased, particularly replacement chemicals that are studied., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Although prior studies have found associations of the ovarian reserve with urinary concentrations of some individual phenols and phthalate metabolites, little is known about the potential associations of these chemicals as a mixture with the ovarian reserve. We investigated whether mixtures of four urinary phenols (bisphenol A, butylparaben, methylparaben, propylparaben) and eight metabolites of five phthalate diesters including di(2-ethylhexyl) phthalate were associated with markers of the ovarian reserve among 271 women attending a fertility center who enrolled in the Environment and Reproductive Health study (2004-2017). The analysis was restricted to one outcome per study participant using the earliest outcome after the last exposure assessment. Ovarian reserve markers included lower antral follicle count (AFC) defined as AFC < 7, circulating serum levels of day 3 follicle stimulating hormone (FSH) assessed by immunoassays, and diminished ovarian reserve (DOR) defined as either AFC < 7, FSH > 10 UI/L or primary infertility diagnosis of DOR. We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation to estimate the joint associations and assess the interactions between chemical exposure biomarkers on the markers of the ovarian reserve while adjusting for confounders. Among all 271 women, 738 urine samples were collected. In quantile g-computation models, a quartile increase in the exposure biomarkers mixture was not significantly associated with lower AFC (OR = 1.10, 95 % CI = 0.52, 2.30), day 3 FSH levels (Beta = 0.30, 95 % CI = -0.32, 0.93) or DOR (OR = 1.02, 95 % CI = 0.52, 2.05). Similarly, BKMR did not show any evidence of associations between the mixture and any of the studied outcomes, or interactions between chemicals. Despite the lack of associations, these results need to be explored among women in other study cohorts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023.)

Study Question: What metabolic pathways and metabolites in the serum and follicular fluid are associated with peak estradiol levels and the number of mature oocytes?, Summary Answer: In the serum metabolome, mostly fatty acid and amino acid pathways were associated with estradiol levels and mature oocytes while in the follicular fluid metabolome, mostly lipid, vitamin, and hormone pathways were associated with peak estradiol levels and mature oocytes., What Is Known Already: Metabolomics has identified several metabolic pathways and metabolites associated with infertility but limited data are available for ovarian stimulation outcomes., Study Design, Size, Duration: A prospective cohort study of women undergoing IVF from 2009 to 2015., Participants/materials, Setting, Methods: A total of 125 women undergoing a fresh IVF cycle at a fertility clinic in the Northeast United States who provided a serum and follicular fluid sample. Untargeted metabolomics profiling was conducted using liquid chromatography with high-resolution mass spectrometry in two chromatography columns (C18 and hydrophilic interaction chromatography (HILIC)). The main ovarian stimulation outcomes were peak serum estradiol levels and number of mature oocytes. We utilized adjusted generalized linear regression models to identify significant metabolic features. Models were adjusted for age,BMI, initial infertility diagnosis, and ovarian stimulation protocol. We then conducted pathway analysis using mummichog and metabolite annotation using level-1 evidence., Main Results and Role of Chance: In the serum metabolome, 480 and 850 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively. Additionally, 437 and 538 features were associated with mature oocytes in the C18 and HILIC columns, respectively. In the follicular fluid metabolome, 752 and 929 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively, Additionally, 993 and 986 features were associated with mature oocytes in the C18 and HILIC columns, respectively. The most common pathways associated with peak estradiol included fatty acids (serum and follicular fluid), hormone (follicular fluid), and lipid pathways (follicular fluid). The most common pathways associated with the number of mature oocytes retrieved included amino acids (serum), fatty acids (serum and follicular fluid), hormone (follicular fluid), and vitamin pathways(follicular fluid). The vitamin D3 pathway had the strongest association with both ovarian stimulation outcomes in the follicularfluid. Four and nine metabolites were identified using level-1 evidence (validated identification) in the serum and follicular fluid metabolomes, respectively., Limitations, Reasons for Caution: Our sample was majority White and highly educated and may not be generalizable to thewider population. Additionally, residual confounding is possible and the flushing medium used in the follicular fluid could have diluted our results., Wider Implications of the Findings: The pathways and metabolites identified by our study provide novel insights into the biologicalmechanisms in the serum and follicular fluid that may underlie follicular and oocyte development, which could potentially be used to improve ovarian stimulation outcomes., Study Funding/competing Interest(s): This work was supported by the following grants from the National Institute of Environmental Health Sciences (P30-ES019776, R01-ES009718, R01-ES022955, P30-ES000002, R00-ES026648, and T32-ES012870), and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK046200). The authors have no competing interests to disclose., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Consumption of energy drinks has increased drastically in recent years, particularly among young people. It is unknown whether intake of energy drinks is associated with health during pregnancy., Objective: To examine associations of energy drink intake before and during pregnancy with risk of adverse pregnancy outcomes (APOs)., Design, Setting, and Participants: This prospective cohort study included data from women enrolled in the Nurses' Health Study 3 (NHS3) between June 1, 2010, and September 27, 2021, and the Growing Up Today Study (GUTS) who reported 1 or more singleton pregnancy from January 1, 2011, to June 1, 2019. Data were analyzed from October 1, 2021, to September 28, 2023., Exposure: Intake of energy drinks, assessed by food frequency questionnaire., Main Outcomes and Measures: The main outcomes were self-reported APOs, including pregnancy loss, gestational diabetes, gestational hypertension, preeclampsia, or preterm birth, and a composite APO, defined as development of any of the APOs. Risk of APOs was compared between consumers and nonconsumers of energy drinks., Results: This study included 7304 pregnancies in 4736 participants with information on prepregnancy energy drink intake and 4559 pregnancies in 4559 participants with information on energy drink intake during pregnancy. There were 1691 GUTS participants (mean [SD] age, 25.7 [2.9] years) and 3045 NHS3 participants (mean [SD] age, 30.2 [4.1] years). At baseline, 230 GUTS participants (14%) and 283 NHS3 participants (9%) reported any intake of energy drinks. While no associations were found for pregnancy loss (odds ratio [OR], 0.89; 95% CI, 0.71-1.11), preterm birth (OR, 1.07; 95% CI, 0.71-1.61), gestational diabetes (OR, 0.89; 95% CI, 0.58-1.35), preeclampsia (OR, 0.73; 95% CI, 0.41-1.30), or the composite APO (OR, 1.05; 95% CI, 0.87-1.26), prepregnancy energy drink use was associated with a higher risk of gestational hypertension (OR, 1.60; 95% CI, 1.12-2.29). A significant interaction was found between age and energy drink intake in relation to hypertensive disorders (P = .02 for interaction for gestational hypertension; P = .04 for interaction for any hypertensive disorders), with stronger associations for participants above the median age. No associations of energy drink intake during pregnancy with any of the APOs were found in NHS3 (eg, any APO: OR, 0.86; 95% CI, 0.41-1.79)., Conclusions and Relevance: In this study, energy drink intake before pregnancy was associated with an elevated risk of gestational hypertension. Given the low prevalence of energy drink intake and low consumption levels among users, the results should be interpreted cautiously.

Importance: Gestational diabetes has been associated with numerous chronic diseases. However, few studies have examined the association of gestational diabetes with long-term mortality risk., Objective: To investigate the associations between gestational diabetes and long-term risks of total and cause-specific mortality., Design, Setting, and Participants: This cohort study analyzed participants of the Nurses' Health Study II who were followed for 30 years (1989-2019). Participants included US female nurses aged 25 to 42 years who reported at least 1 pregnancy (≥6 months) at 18 years or older across their reproductive life span. Data were analyzed from May 1, 2022, to May 25, 2023., Exposure: Gestational diabetes across the reproductive life span., Main Outcomes and Measures: Hazard ratios (HRs with 95% CIs) for total and cause-specific mortality were estimated by Cox proportional hazards regression models., Results: A total of 91 426 parous participants were included, with a mean (SD) age of 34.9 (4.7) years and a body mass index of 24.1 (4.7) at baseline. During a follow-up period of 2 609 753 person-years, 3937 deaths were documented, including 255 deaths from cardiovascular disease and 1397 from cancer. Participants with a history of gestational diabetes had a higher crude mortality rate than those without a history of gestational diabetes (1.74 vs 1.49 per 1000 person-years; absolute difference = 0.25 per 1000 person-years). The corresponding HR for total mortality was 1.28 (95% CI, 1.13-1.44), which did not materially change after additional adjustment for potential confounders and lifestyle factors during the reproductive life span (HR, 1.25; 95% CI, 1.11-1.41). The association persisted regardless of the subsequent development of type 2 diabetes and was more robust among participants who adopted less healthy lifestyles; experienced gestational diabetes in 2 or more pregnancies (HR, 1.48; 95% CI, 0.99-2.19); had gestational diabetes both in the initial and subsequent pregnancies (HR, 1.71; 95% CI, 1.11-2.63); and concurrently reported hypertensive disorders in pregnancy (HR, 1.80; 95% CI, 1.21-2.67), preterm birth (HR, 2.46; 95% CI, 1.66-3.64), or low birth weight (HR, 2.11; 95% CI, 1.21-3.68). Cause-specific mortality analyses revealed that gestational diabetes was directly associated with the risk of mortality due to cardiovascular disease (HR, 1.59; 95% CI, 1.03-2.47). Additionally, gestational diabetes was inversely associated with cancer mortality (HR, 0.76; 95% CI, 0.59-0.98); however, it was only evident among participants who later developed type 2 diabetes., Conclusions and Relevance: Results of this cohort study suggest that participants who reported a history of gestational diabetes exhibited a small but elevated risk of subsequent mortality over 30 years. The findings emphasize the importance of considering gestational diabetes as a critical factor in later-life mortality risk.

The dietary supplements industry disproportionately markets potentially harmful products promising weight loss, cleansing/detoxing, and boosted energy and immunity to women. The COVID-19 pandemic heightened consumer concerns around health and body weight, which may have increased women's risks of using supplements, particularly if they had a higher weight and experienced weight discrimination. This study aimed to estimate inequities in prevalence and change in use of weight-loss, cleanse/detox, immunity, and energy supplements in the first year of the pandemic and to assess the extent to which the relationship between weight and supplement use differs across discrimination experiences. We drew upon longitudinal data from cisgender women in the U.S. COVID-19 Pandemic Substudy of the Nurses' Health Study II and 3 and Growing Up Today Study cohorts, collected over 5 waves from April/May 2020 to April 2021 (N = 51,814). Modified Poisson generalized estimating equation models, adjusted for age, cohort, race/ethnicity, wave, and Census region, estimated the relative excess risk due to interaction (RERI) between weight status and weight discrimination on prevalence of supplement use. Weight status categories were derived from body mass index (BMI), and weight discrimination was assessed using the attributions item of the Everyday Discrimination Scale. Baseline prevalence of supplement use was 2.7% for weight-loss, 3.3% for cleanse/detox, 4.2% for energy, and 22.6% for immune. Respondents with BMIs of 25-29.9 kg/m 2 and 30-34.9 kg/m 2 who experienced weight discrimination had RERI values of 0.89 (95% CI 0.14, 1.65) and 1.00 (95% CI 0.25, 1.75) for weight-loss and 0.57 (95% CI 0.13, 1.02) and 0.60 (95% CI 0.19, 1.01) for energy supplements, respectively, indicating this group had excess risk of use compared to lower BMI respondents who experienced no weight discrimination. The findings demonstrate the disproportionate impact of weight discrimination on use of potentially harmful supplements among cisgender women with higher weights during the pandemic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Adherence to healthy lifestyles can be beneficial for depression among adults, but the intergenerational impact of maternal healthy lifestyles on offspring depressive symptoms is unknown., Methods: In total, 10 368 mothers in Nurses' Health Study II and 13 478 offspring in the Growing Up Today Study were paired. Maternal and offspring healthy lifestyles were defined as a composite score including a healthy diet, normal body mass index (BMI), never-smoking, light-to-moderate consumption of alcohol, and regular moderate-to-vigorous physical activity. Maternal lifestyles were assessed during their offspring's childhood. Offspring depressive symptoms were repeatedly assessed five times using the Center for Epidemiological Studies Depression Scale-10 (CESD-10); the offspring were between the ages of 14 and 30 when the first CESD-10 was assessed. Covariates included maternal variables (age at baseline, race/ethnicity, antidepressant use, pregnancy complications, etc.) and offspring age and sex., Results: Children of mothers with the healthiest lifestyle had significantly fewer depressive symptoms (a 0.30 lower CESD-10 score, 95% confidence interval (CI) 0.09-0.50) in comparison with children of mothers with the least healthy lifestyle. The association was only found significant in female offspring but not in males. For individual maternal lifestyle factors, a normal BMI, never-smoking, and adherence to regular physical activity were independently associated with fewer depressive symptoms among the offspring. The association between maternal healthy lifestyles and offspring depressive symptoms was mediated by offspring's healthy lifestyles (mediation effect: 53.2%, 95% CI 15.8-87.3)., Conclusions: Our finding indicates the potential mechanism of intergenerational transmission of healthy lifestyles to reduce the risk of depressive symptoms in offspring.

Background: It remains unclear whether in utero and childhood exposure to air pollution affects pubertal development, particularly age of menarche in girls., Objective: The aim of this study was to determine whether residential ambient particulate matter (PM) exposure in utero and during childhood is associated with age of menarche., Methods: We studied 5,201 girls in the Growing Up Today Study 2 (2004-present) who were 10-17 y of age at enrollment (47.7% premenarchal; 52.3% postmenarchal). Exposure to three size fractions of PM [fine PM with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ), PM with aerodynamic diameters between  2.5 μ m  and  10 μ m ( PM 2.5 - 10 ), and PM with aerodynamic diameter 10 μ m ( PM 10 )] was assigned based on maternal residential address, updated every 2 y, using nationwide spatiotemporal models. We estimated average PM exposure in utero , and time-varying windows: annual average exposure in the prior 1 and 2 y and cumulative average from birth. Age of menarche was self-reported on three surveys administered in 2004, 2006, and 2008. We calculated hazard ratios (HR) for menarche for an interquartile range (IQR) increase in PM exposure using Cox proportional hazard models adjusting for potential confounders., Results: Girls attained menarche at 12.3 y of age on average. In the adjusted model, higher residential exposure to ambient PM 2.5 during all time windows was associated with earlier age of menarche. The HRs of menarche for each IQR ( 4   μ g / m 3 ) increase in exposure to PM 2.5 during the in utero period, 1 y prior to menarche, and throughout childhood were 1.03 [95% confidence interval (CI): 1.00, 1.06], 1.06 (95% CI: 1.02, 1.10) and 1.06 (95% CI: 1.02, 1.10), respectively. Effect estimates for PM 10 exposure were similar, albeit attenuated, for all time windows. PM 2.5 - 10 exposure was not associated with age of menarche., Discussion: Among a large, nationwide, prospective cohort of U.S. girls, higher exposure to PM 2.5 and PM 10 in utero and throughout childhood was associated with an earlier age of menarche. Our results suggest that PM 2.5 and PM 10 may have endocrine-disrupting properties that could lead to altered timing of menarche. https://doi.org/10.1289/EHP12110.

Objective: The aim of the study is to examine longitudinal associations of history of infertility with menopausal symptoms in midlife., Methods: Six hundred ninety-five midlife women (≥45 y old or reporting ≥12 mo of amenorrhea at the midlife visit) in Project Viva, a prospective cohort enrolled 1999-2002 during pregnancy and followed for 18 years after enrollment ("midlife visit"). Exposure was history of infertility defined as time to pregnancy ≥12 months (≥6 mo if ≥35 y), use of medical treatment to conceive, or infertility consultation or treatment in the 6-month preceding enrollment. The primary outcome was score below or above the median on the Menopause Rating Scale (MRS). Secondary outcomes included individual symptom score on the MRS and self-reported age of menopause., Results: A total of 36.6% had a history of infertility in their lifetime. At the time of MRS completion, the women with prior infertility were older (53.4 [SD, 3.8] vs 51.2 [SD, 3.7] y) than those without infertility and a larger proportion had reached menopause (62% vs 40%). Women with prior infertility were more likely to score above the median on the MRS (Adjusted Odds Ratio [aOR], 1.45; 95% confidence interval [CI], 1.04-2.01) and had higher odds for reporting any depressive mood (aOR, 1.56; 95% CI, 1.12-2.16) and irritability (aOR, 1.57; 95% CI, 1.13-2.19). There was a trend toward greater severity of sleep problems among women with prior infertility. There was no association of prior infertility with report of other menopausal symptoms or age of menopause., Conclusions: Our findings suggest that women with prior infertility are more likely to have an MRS score above the median and experience depressive mood, irritability, and sleep problems during midlife than women without infertility. These findings have implications for mental health screening among midlife women., Competing Interests: Financial disclosures/conflicts of interest: J.L.S. receives funding from Harvard Pilgrim Health Care for consulting related to research. J.E.C. has no disclosures relevant to this manuscript but does receive grants from the Food and Drug Administration and National Institutes of Health unrelated to this work. In addition, in the last 5 years, JEC has received royalties from Harvard Health Publications and payment for lectures and/or support for attending conferences from Johns Hopkins University, NIH, Northwestern, Carolinas Medical Center, ASRM, British Dietetic Association, PCRS, Tufts University, ESHRE, Institut Hospital del Mar d'Investigacion Mediques, Japanese Society for Reproductive Medicine, Lund University Faculty of Medicine, and Medical University of Vienna, (Copyright © 2023 by The North American Menopause Society.)

Objective: This study aimed to evaluate the associations of age at first birth and parity with weight, waist circumference (WC), and body fat across midlife., Methods: A secondary data analysis was conducted with 735 participants from Project Viva who reported their age at first birth and lifetime parity at a midlife study visit. Weight, WC, and body fat were measured up to four times after the participants' final birth, and associations were examined using linear mixed-effects regression models., Results: Participants' mean (SD) age was 32.6 (4.9) years at enrollment and 30.4 (5.5) years at their first birth, and they had 2.4 (0.9) lifetime births. In adjusted models, women who had their first birth at age <23 or ≥40 years, versus age 30 to 34 years, had a higher trajectory of weight, WC, and body fat after their final birth (i.e., mean differences in weight 8.38 kg [95% CI: 4.13-12.63] for age <23 years and 6.54 kg [95% CI: 0.64-12.45] for age ≥40 years). Women with four or more births, versus two, had a higher trajectory of adiposity after accounting for covariates., Conclusions: Women who have a first birth before age 23 years or after age 40 years and those with multiple births may benefit from more intensive monitoring for excess adiposity gain., (© 2023 The Obesity Society.)

Background: Fertility-awareness-based methods have been linked to shorter time to conception; however, little is known about the predictors of fertility-awareness-based method use among women who are currently or will soon be trying to conceive., Objectives: The aim of this study was to identify predictors of fertility-awareness-based methods use among women trying to conceive or contemplating pregnancy within the next year., Methods: Women participating in the Nurses' Health Study 3 were asked if they were trying to become pregnant or contemplating pregnancy and whether they are using fertility-awareness-based methods. Multivariable negative binomial regression was used to identify predictors for a number of fertility-awareness-based methods used., Results: Among the 23,418 women asked about pregnancy intention since 2015, 955 were trying to conceive, and 2,282 were contemplating pregnancy within the next year. The three most used fertility-awareness-based methods among women trying to conceive were menstrual cycle tracking, ovulation prediction kits, and cervical mucus monitoring. Among women contemplating pregnancy, the three most commonly used methods were menstrual cycle tracking, cervical mucus monitoring, and basal body temperature monitoring. The ongoing duration of pregnancy attempts and gravidity were associated with the number of methods used among women actively trying to conceive. When compared with women who were trying for 2 months or less, the number of methods was 29% higher when trying for 3-5 months, 45% higher when trying for 6-12 months, and 38% higher when trying for more than 1 year. Compared with nulligravid women, the number of methods was lower for women with a history of two or more pregnancies. Among women contemplating pregnancy, those who were married or in a domestic partnership used more fertility-awareness-based methods than unpartnered women. No other significant predictors of fertility-awareness-based method use were identified., Discussion: Duration of ongoing pregnancy attempt and gravidity were the only significant predictors for the number of fertility-awareness-based methods used among women actively trying to conceive, whereas partnership was the only significant predictor of the number of fertility-awareness-based methods among women contemplating pregnancy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Increasing evidence suggests that specific foods and nutrients may improve infertility treatment outcomes in women. However, less is known about the role of dietary patterns., Objective: To investigate whether women's adherence to a priori-defined dietary patterns promoted for the prevention of chronic conditions is associated with outcomes of infertility treatment., Design, Setting, and Participants: This prospective cohort study was conducted at a fertility center at an academic medical center in Boston, Massachusetts. Women undergoing infertility treatment cycles, including intrauterine insemination cycles and in vitro fertilization with or without intracytoplasmic sperm injection were included. Data were collected from January 2007 to October 2019, and data were analyzed from February to December 2022., Exposures: Women's pretreatment diet was assessed with a validated food frequency questionnaire from which 8 a priori-defined scores were calculated (higher score indicates greater adherence): (1) Trichopoulou Mediterranean diet, (2) alternate Mediterranean diet, (3) Panagiotakos Mediterranean diet, (4) Healthy Eating Index, (5) Alternate Healthy Eating Index, (6) American Heart Association (AHA) index, (7) Dietary Approaches to Stop Hypertension index, and (8) plant-based diet., Main Outcomes and Measures: The adjusted probability of clinically relevant outcomes (live birth as a primary outcome and clinical pregnancy and pregnancy loss as secondary outcomes) was evaluated across quartiles of adherence to each dietary pattern using multivariable generalized linear mixed models to account for repeated cycles., Results: This analysis included 612 women with a median (IQR) age of 35.0 (32.0-38.0) years. There was no association between women's adherence to the 8 a priori dietary patterns and probability of clinical pregnancy or live birth following in vitro fertilization or intrauterine insemination. However, an inverse association was found between adherence to AHA dietary pattern and risks of total and clinical pregnancy loss. Among women who became pregnant during the course of infertility treatment, the adjusted probabilities of pregnancy loss in the lowest and highest quartile of the AHA dietary pattern were 0.41 (95% CI, 0.33-0.50) and 0.28 (95% CI, 0.21-0.36), respectively (P for trend = .02). The corresponding adjusted probabilities of clinical pregnancy loss were 0.30 (95% CI, 0.22-0.39) and 0.15 (95% CI, 0.10-0.23) (P for trend = .007). A similar pattern was observed for all other dietary patterns, with the exception of the plant-based diet pattern., Conclusions and Relevance: Findings of this cohort study suggest that preconception adherence to the AHA diet may be associated with a lower likelihood of pregnancy loss during the course of infertility treatment.

Study Question: Is there an association between iron intake and ovarian reserve among women seeking fertility care?, Summary Answer: Supplemental iron intake above 45 mg/day is associated with lower ovarian reserve among women seeking fertility care., What Is Known Already: Although the literature regarding iron intake in relation to ovarian reserve is scant and inconsistent, some evidence suggests that iron may have gonadotoxic effects., Study Design, Size, Duration: This observational study included 582 female participants attending the Massachusetts General Hospital Fertility Center (2007-2019) enrolled in the Environment and Reproductive Health (EARTH) Study., Participants/materials, Setting, Methods: Iron intake was estimated using a validated food frequency questionnaire. Markers of ovarian reserve included antral follicle count (AFC) (assessed via transvaginal ultrasound) and Day 3 FSH, both obtained during the course of an infertility evaluation., Main Results and the Role of Chance: Participants had a median age of 35 years and median total iron intake of 29 mg/day. Total iron intake was inversely related to AFC and this association was driven by intake of supplemental iron. Compared to women with a supplemental iron intake of ≤20 mg/day, women consuming 45-64 mg/day of supplemental iron had a 17% (-35%, 0.3%) lower AFC and women consuming ≥65 mg/day of supplemental iron had a 32% (-54%, -11%) lower AFC after adjusting for potential confounders (P, linear trend = 0.003). Similarly, in a multivariable-adjusted analysis, Day 3 FSH levels were 0.9 (0.5, 1.3) IU/ml higher among women with a supplemental iron intake of ≥65 mg/day when compared to women with a supplemental iron intake of ≤20 mg/day (P, linear trend = 0.02)., Limitations, Reasons for Caution: Iron intake was estimated using a method that relies on self-report and we had no biomarkers of iron status in our participants; only 36 women consumed ≥45 mg/day of supplemental iron., Wider Implications of the Findings: Since all study participants were seeking fertility treatment, our findings may not apply to women in the general population. Although our findings are consistent with studies of women with iron overload, given the paucity of literature on this topic, it is essential that this question is revisited in studies designed to better understand the dose-response relation of this association across the entire distribution of ovarian reserve and the risk-benefit balance of pre-conceptional iron supplementation given its many positive effects on pregnancy outcomes., Study Funding/competing Interest(s): The project was funded by Grants R01ES022955, R01ES033651, R01ES009718, P30ES000002, and P30DK046200 from the National Institutes of Health. N.J.-C. was supported by a Fulbright Scholarship. N.J.-C., M.M., L.M.-A., E.O.-P., S.W., I.S., and J.E.C. declare no conflict of interest related to the work in the manuscript. R.H. has received grants from the National Institute of Environmental Health Sciences., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Pre-pandemic psychological distress is associated with increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but associations with the coronavirus disease 2019 (COVID-19) severity are not established. The authors examined the associations between distress prior to SARS-CoV-2 infection and subsequent risk of hospitalization., Methods: Between April 2020 (baseline) and April 2021, we followed 54 781 participants from three ongoing cohorts: Nurses' Health Study II (NHSII), Nurses' Health Study 3 (NHS3), and the Growing Up Today Study (GUTS) who reported no current or prior SARS-CoV-2 infection at baseline. Chronic depression was assessed during 2010-2019. Depression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at baseline. SARS-CoV-2 infection and hospitalization due to COVID-19 was self-reported. Relative risks (RRs) were calculated by Poisson regression., Results: 3663 participants reported a positive SARS-CoV-2 test (mean age = 55.0 years, standard deviation = 13.8) during follow-up. Among these participants, chronic depression prior to the pandemic [RR = 1.72; 95% confidence interval (CI) 1.20-2.46], and probable depression (RR = 1.81, 95% CI 1.08-3.03), being very worried about COVID-19 (RR = 1.79; 95% CI 1.12-2.86), and loneliness (RR = 1.81, 95% CI 1.02-3.20) reported at baseline were each associated with subsequent COVID-19 hospitalization, adjusting for demographic factors and healthcare worker status. Anxiety and perceived stress were not associated with hospitalization. Depression, worry about COVID-19, and loneliness were as strongly associated with hospitalization as were high cholesterol and hypertension, established risk factors for COVID-19 severity., Conclusions: Psychological distress may be a risk factor for hospitalization in patients with SARS-CoV-2 infection. Assessment of psychological distress may identify patients at greater risk of hospitalization. Future work should examine whether addressing distress improves physical health outcomes.

Objective: To investigate the association between infertility and the incidence of invasive cancer., Design: Prospective cohort study (1989-2015)., Setting: Not applicable., Patient(s): A total of 103,080 women aged 25-42 years in the Nurses' Health Study II who were cancer-free at baseline (1989)., Intervention(s): The infertility status (failure to conceive after 1 year of regular, unprotected sex) and causes of infertility were self-reported at baseline and biennial follow-up questionnaires., Main Outcome Measure(s): Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian, and postmenopausal breast) or non-obesity-related (all other cancers). We fit the Cox proportional-hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between infertility and cancer incidence., Result(s): During 2,149,385 person-years of follow-up, 26,208 women reported a history of infertility, and we documented 6,925 incident invasive cancer cases. After adjusting for body mass index and other risk factors, women who reported infertility had a higher risk of developing cancer than gravid women without a history of infertility (HR, 1.07; 95% CI, 1.02-1.13). This association was stronger among obesity-related cancers (HR, 1.13; 95% CI, 1.05-1.22; vs. non-obesity-related cancers, HR, 0.98; 95% CI, 0.91-1.06) and, in particular, obesity-related reproductive cancers (postmenopausal breast, endometrial, and ovarian cancers; HR, 1.17; 95% CI, 1.06-1.29) and was stronger among women who first reported infertility earlier in life (≤25 years, HR, 1.19; 95% CI, 1.07-1.33; 26-30 years, HR, 1.11; 95% CI, 0.99-1.25; >30 years, HR, 1.07; 95% CI, 0.94-1.22; P trend < .001)., Conclusion(s): A history of infertility may be associated with the risk of developing obesity-related reproductive cancers; further study is needed to elucidate the underlying mechanisms., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Energy drinks are consumed for a variety of reasons, including to boost mental alertness and energy. We assessed associations between demographic factors and various high-risky behaviours with energy drink consumption as they may be linked to adverse health events., Design: We conducted cross-sectional analysis including basic descriptive and multivariable-adjusted logistic regression analyses to characterise demographic and behavioural factors (including diet quality, binge drinking and illicit drug use, among others obtained via questionnaires) in relation to energy drink consumption., Setting: We used data from two large US-based cohorts., Participants: 46 390 participants from Nurses' Health Study 3 (NHS3, n 37 302; ages 16-31) and Growing Up Today Study (GUTS, n 9088, ages 20-55)., Results: Of the 46 390 participants, 13·2 % reported consuming ≥ 1 energy drink every month. Several risky behaviours were associated with energy drink use, including illegal drug use (pooled OR, pOR: 1·45, 95 % CI: 1·16, 1·81), marijuana use (pOR: 1·49, 95 % CI: 1·28, 1·73), smoking (pOR: 1·88. 95 % CI: 1·55, 2·29), tanning bed use (pOR: 2·31, 95 % CI: 1·96, 2·72) and binge drinking (pOR: 2·53, 95 % CI: 2·09, 3·07). Other factors, such as high BMI, e-cigarette use and poor diet quality were found to be significantly associated with higher energy drink consumption ( P values < 0·001)., Conclusions: Our findings show that energy drink consumption and high-risk behaviours may be related, which could potentially serve as not only as a talking point for providers to address in outreach and communications with patients, but also a warning sign for medical and other health practitioners.

Background: Hypertensive disorders of pregnancy (HDPs) have been associated with respiratory dysfunction during pregnancy and postpartum. In this study, we explored the associations between HDPs (gestational hypertension and preeclampsia) and the risk of incident asthma and chronic obstructive pulmonary disease (COPD) during adulthood and the potential mediating role of chronic hypertension., Methods: We included parous nurses in the Nurses' Health Study II reporting a pregnancy lasting no less than 6 months. The associations between HDPs and asthma and COPD were estimated using Cox proportional hazards models with adjustment for confounders., Findings: We included 73,807 nurses [92.5% (68,246 of 73,807) White] in asthma analyses and 79,843 [92.4% (73,746 of 79,843) White] in COPD analyses, whose mean (SD, range) age, at baseline, were both 34.8 (4.7, 25.0-44.0) years. During 24 years of follow-up, we identified 2663 incident cases of asthma and 537 COPD. Compared with nurses without HDPs, nurses reporting HDPs had an increased HR for incident asthma and COPD of 1.22 (95% CI 1.10-1.36) and 1.39 (95% CI 1.11-1.74), respectively. The risk of asthma was similar when gestational hypertension and preeclampsia were assessed separately [HR = 1.25 (95% CI 1.08-1.43) and 1.24 (95% CI 1.11-1.38), respectively]. However, only nurses with preeclampsia had a higher risk of COPD (HR = 1.41, 95% CI 1.11-1.78). Mediation analyses estimated that chronic hypertension explained 18.6% (95% CI 8.9-35.0%) and 10.7% (95% CI 2.9-32.4%) of the associations between HDPs and asthma and COPD, respectively., Interpretation: HDPs may serve as useful markers of increased susceptibility to chronic respiratory diseases during adulthood., Funding: The National Institutes of Health grants., Competing Interests: JEC and CAC report financial support from the 10.13039/100000002National Institutes of Health, outside the submitted work. All other authors declare no competing interests., (© 2023 The Authors.)

The associations between urinary phenol concentrations and markers of thyroid function and autoimmunity among potentially susceptible subgroups, such as subfertile women, have been understudied, especially when considering chemical mixtures. We evaluated cross-sectional associations of urinary phenol concentrations, individually and as a mixture, with serum markers of thyroid function and autoimmunity. We included 339 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2009-2015). We quantified four phenols in urine using isotope dilution high-performance liquid chromatography-tandem mass spectrometry, and biomarkers of thyroid function (thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4), and triiodothyronine (fT3, TT3)), and autoimmunity (thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (Ab)) in serum using electrochemoluminescence assays. We fit linear and additive models to investigate the association between urinary phenols-both individually and as a mixture-and serum thyroid function and autoimmunity, adjusted for confounders. As a sensitivity analysis, we also applied Bayesian Kernel Machine Regression (BKMR) to investigate non-linear and non-additive interactions. Urinary bisphenol A was associated with thyroid function, in particular, fT 3 (mean difference for a 1 log unit increase in concentration: -0.088; 95% CI [-0.151, -0.025]) and TT 3 (-0.066; 95% CI [-0.112, -0.020]). Urinary methylparaben and triclosan were also associated with several thyroid hormones. The overall mixture was negatively associated with serum fT 3 concentrations (mean difference comparing all four mixture components at their 75th vs. 25th percentiles: -0.19, 95% CI [-0.35, -0.03]). We found no evidence of non-linearity or interactions. These results add to the current literature on phenol exposures and thyroid function in women, suggesting that some phenols may alter the thyroid system.

Objective: To investigate the association between intake of soy food and isoflavone with ovarian reserve. Previous studies suggest on the relationship between soy intake and human fertility are inconsistent. Some clinical studies suggest that soy and phytoestrogens may not be deleterious to reproduction and may even be beneficial in couples undergoing infertility treatment. However, no studies have evaluated the relationship between soy or isoflavone intake with markers of ovarian reserve other than follicle-stimulating hormone (FSH)., Design: Cross-sectional study., Setting: An academic fertility center., Patient(s): Patients presenting to an academic fertility center between 2007 and 2019 were invited to participate in the Environment and Reproductive Health Study., Intervention(s): Six hundred and sixty seven participants reported their soy food intake and had an antral follicle count (AFC) assessment. Intake of 15 soy-based foods during the previous 3 months was obtained at baseline and intake of isoflavone was estimated. Participants were divided into 5 groups based on soy food and isoflavone intake considering those who did not consume soy as the reference group., Main Outcome Measure(s): Ovarian reserve was assessed using AFC as the primary outcome measure, with antimüllerian hormone (AMH) and FSH as secondary outcome measures. The AFC was measured on the third day of the menstrual cycle. Moreover, FSH and AMH levels were measured in blood samples obtained on the third day and the follicular phase of the menstrual cycle. To evaluate the association between soy intake and ovarian reserve, we used Poisson regression models for AFC and quantile regression models for AMH and day 3 FSH levels by adjusting for confounders., Result(s): Participants had a median age of 35.0 years. The median intake of soy was 0.09 servings/day and isoflavones was 1.78 mg/day. Moreover, AFC, AMH, and FSH were unrelated to soy intake in crude analyses. We found no association between soy food intake with AFC or day 3 FSH level in multivariable models. However, participants in the highest category of soy food intake had significantly low AMH levels (-1.16, 95% confidence interval: -1.92, -0.41). Soy intake had no association with AFC, AMH, or FSH in sensitivity analyses that included using different cutoff points of soy intake, excluding participants in the highest 2.5 percentile of intake, and additional statistical adjustment for dietary patterns., Conclusion(s): The results of this study are not consistent with a strong positive or inverse association of soy or isoflavone intakes within the observed range of intake, which substantially overlaps with that in the general population of the United States as well as the ovarian reserve among individuals presenting to fertility centers., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Research Question: Is self-reported psychological stress associated with markers of ovarian reserve among subfertile women?, Design: Observational study of women (n = 520) seeking fertility care at the Massachusetts General Hospital who enrolled in the Environment and Reproductive Health study between 2005 and 2019. Women completed the short version of the validated PSS4, which assesses psychological stress. Ovarian reserve markers included AFC and circulating serum levels of day-3 FSH, with AMH assessed in a subset of participants (n = 185)., Results: Higher total PSS4 scores were negatively associated with AFC and serum AMH levels. Analyses adjusted for age, BMI, race, smoking, education, physical activity and type of infertility diagnosis. Women in the second and third tertiles of stress had lower AFC (13.3, 95% CI 12.7 to 13.8; and 13.5, 95% CI 13.0 to 14.1) compared with women in the lowest tertile of psychological stress score (14.3, 95% CI 13.8 to 14.9, both P < 0.05). Women in the second and third tertiles of total PSS4 scores also had lower mean serum AMH compared with women in the lowest tertile (2.99, 95% CI 2.24 to 3.74), and (2.99 95% CI 2.22 to 3.76) versus (3.94 95% CI 3.23 to 4.64). These associations varied by several socioeconomic factors, and were observed among women who were younger, belonging to minority races, with a college degree or with annual household income less than $100,000., Conclusions: Higher perceived stress was negatively associated with AFC and serum AMH levels. These associations varied by several socioeconomic factors., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Women are at greater risk than men of developing chronic inflammatory conditions and "long COVID." However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19., Objective: This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19., Study Design: We followed 46,579 women from 2 ongoing prospective cohort studies-the Nurses' Health Study II and the Nurses' Health Study 3-who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases)., Results: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44-65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05-1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00-1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01-1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis., Conclusion: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To explore associations between early life physical and sexual abuse and subsequent risk of premature mortality (death before age 70 years)., Design: Prospective cohort study., Setting: The Nurses' Health Study II (2001-19)., Participants: 67 726 female nurses aged 37-54 years when completing a violence victimization questionnaire in 2001., Main Outcome Measures: Hazard ratios and 95% confidence intervals for total and cause specific premature mortality by childhood or adolescent physical and sexual abuse, estimated by multivariable Cox proportional hazard models., Results: 2410 premature deaths were identified over 18 years of follow-up. Nurses who experienced severe physical abuse or forced sexual activity in childhood and adolescence had a higher crude premature mortality rate than nurses without such abuse in childhood or adolescence (3.15 v 1.83 and 4.00 v 1.90 per 1000 person years, respectively). The corresponding age adjusted hazard ratios for premature deaths were 1.65 (95% confidence interval 1.45 to 1.87) and 2.04 (1.71 to 2.44), respectively, which were materially unchanged after further adjusting for personal characteristics and early life socioeconomic status (1.53, 1.35 to 1.74, and 1.80, 1.50 to 2.15, respectively). Cause specific analyses indicated that severe physical abuse was associated with a greater risk of mortality due to external causes of injury and poisoning (multivariable adjusted hazard ratio 2.81, 95% confidence interval 1.62 to 4.89), suicide (3.05, 1.41 to 6.60), and diseases of the digestive system (2.40, 1.01 to 5.68). Forced sexual activity as a child and adolescent was associated with greater risk of mortality due to cardiovascular disease (2.48, 1.37 to 4.46), external injury or poisoning (3.25, 1.53 to 6.91), suicide (4.30, 1.74 to 10.61), respiratory disease (3.74, 1.40 to 9.99), and diseases of the digestive system (4.83, 1.77 to 13.21). The association of sexual abuse with premature mortality was stronger among women who smoked or had higher levels of anxiety during adulthood. Smoking, low physical activity, anxiety, and depression each explained 3.9-22.4% of the association between early life abuse and premature mortality., Conclusion: Early life physical and sexual abuse could be associated with a greater risk of adult premature mortality., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institutes of Health for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The association of multiple healthy sleep dimensions with post-COVID-19 condition (PCC), also known as long COVID, has not been investigated., Objective: To examine whether multidimensional sleep health before and during the COVID-19 pandemic, prior to SARS-CoV-2 infection, was associated with the risk of PCC., Design, Setting, and Participants: This prospective cohort study (2015-2021) included Nurses' Health Study II participants who reported testing positive (n = 2303) for SARS-CoV-2 infection in a substudy series of COVID-19-related surveys (n = 32 249) between April 2020 and November 2021. After exclusion for incomplete information about sleep health and nonresponse to a question about PCC, 1979 women were included in the analysis., Exposures: Sleep health was measured both before (June 1, 2015, to May 31, 2017) and early (April 1 to August 31, 2020) in the COVID-19 pandemic. Prepandemic sleep score was defined according to 5 dimensions: morning chronotype (assessed in 2015), 7 to 8 hours of sleep per day, low insomnia symptoms, no snoring, and no frequent daytime dysfunction (all assessed in 2017). On the first COVID-19 substudy survey (returned between April and August 2020), average daily sleep duration and sleep quality for the past 7 days were queried., Main Outcomes and Measures: SARS-CoV-2 infection and PCC (≥4 weeks of symptoms) were self-reported during 1 year of follow-up. Comparisons were examined between June 8, 2022, and January 9, 2023, using Poisson regression models., Results: Of the 1979 participants reporting SARS-CoV-2 infection (mean [SD] age, 64.7 [4.6] years; 1979 [100%] female; and 1924 [97.2%] White vs 55 [2.8%] other races and ethnicities), 845 (42.7%) were frontline health care workers, and 870 (44.0%) developed PCC. Compared with women who had a prepandemic sleep score of 0 or 1 (least healthy), those who scored 5 (most healthy) had a 30% lower risk of developing PCC (multivariable-adjusted relative risk, 0.70; 95% CI, 0.52-0.94; P for trend <.001). Associations did not differ by health care worker status. No or little daytime dysfunction prepandemic and good sleep quality during the pandemic were independently associated with a lower risk of PCC (relative risk, 0.83 [95% CI, 0.71-0.98] and 0.82 [95% CI, 0.69-0.99], respectively). Results were similar when PCC was defined as having 8 or more weeks of symptoms or as having ongoing symptoms at the time of PCC assessment., Conclusions and Relevance: The findings indicate that healthy sleep measured prior to SARS-CoV-2 infection, both before and during the COVID-19 pandemic, may be protective against PCC. Future research should investigate whether interventions on sleep health may prevent PCC or improve PCC symptoms.

Purpose: Research on infertility and risk of breast cancer has been conflicting, potentially because many well-established breast cancer risk factors, such as pregnancy history, are strongly correlated with infertility., Methods: We followed participants in the Nurses' Health Study II from 1989 to 2015 (n = 103,080) for the development of invasive breast cancer and calculated Hazard Ratios (HR) and 95% confidence intervals (CI) using Cox regression. Participants with a self-reported history of infertility (12 months of trying without conception) were compared to gravid women with no history of infertility. We classified breast cancer by menopausal status and investigated mediation by reproductive factors., Results: Over 26 years of follow-up, 26,208 (25.4%) women reported a history of infertility, and 3,201 women were newly diagnosed with invasive breast cancer. We observed no association between infertility history and risk of overall breast cancer (HR: 1.05, 95% CI: 0.97-1.14) or premenopausal breast cancer (RR: 0.93, 95% CI: 0.83-1.03). However, we observed a modest association between history of infertility and risk of postmenopausal breast cancer (HR: 1.13, 95% CI: 1.00-1.28), approximately 50% of which could be attributed to lower total parity and later age at first birth (95% CI: 8.2%-91.0%)., Conclusions: Women with a history of infertility were at increased risk of postmenopausal breast cancer. Older age at first birth and lower total parity explained approximately half of the association between infertility and risk of postmenopausal breast cancer., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Pregnancy intention assessment is a key element of preconception and contraceptive care. The association between a single screening question and the incidence of pregnancy is unknown., Objective: To prospectively evaluate the dynamics of pregnancy intention and pregnancy incidence., Design, Setting, and Participants: This prospective cohort study (the Nurses' Health Study 3) was conducted from June 1, 2010, to April 1, 2022, in 18 376 premenopausal, nonpregnant female nurses aged 19 to 44 years., Main Outcomes and Measures: Pregnancy intention and pregnancy status were assessed at baseline and approximately every 3 to 6 months thereafter. Cox proportional hazards regression models were used to estimate the association between pregnancy intention and pregnancy incidence., Results: A total of 18 376 premenopausal, nonpregnant women (mean [SD] age, 32.4 [6.5] years) participated in the study. At baseline, 1008 women (5.5%) were trying to conceive, 2452 (13.3%) were contemplating pregnancy within 1 year, and the remaining 14 916 (81.2%) were neither trying to conceive nor thought they would be pregnant within 1 year. A total of 1314 pregnancies were documented within 12 months of pregnancy intention assessment. The cumulative incidence of pregnancy was 38.8% in women actively trying to conceive (median [IQR] time to pregnancy, 3.3 [1.5-6.7] months), 27.6% in women contemplating pregnancy (median [IQR] time to pregnancy, 6.7 [4.2-9.3] months), and 1.7% in women neither trying to conceive nor contemplating pregnancy (median [IQR] time to pregnancy, 7.8 [5.2-10.5] months) among those who became pregnant. Women who were actively trying to conceive were 23.1 times (95% CI, 19.5-27.4 times) and women who were contemplating pregnancy were 13.0 times (95% CI, 11.1-15.2 times) more likely to conceive within 12 months than women who were neither attempting nor contemplating pregnancy. Among women contemplating pregnancy at baseline who did not get pregnant during follow up, 18.8% were actively trying and 27.6% were not trying by 12 months. Conversely, only 4.9% of women neither trying to conceive nor contemplating pregnancy within 1 year at baseline changed pregnancy intention during follow up., Conclusions and Relevance: In this cohort study of reproductive-aged nurses in North America, pregnancy intention was highly fluid among women who were contemplating pregnancy but relatively stable among women trying to conceive and women who were neither trying to conceive nor contemplating pregnancy. Pregnancy intention was strongly associated with pregnancy incidence, but the median time to pregnancy points to a relatively short time window to initiate preconception care.

Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Study Question: Are occupational factors associated with markers of testicular function among men attending a fertility center?, Summary Answer: Men working non-daytime/rotating shifts and those with physically demanding jobs have higher sperm concentration and total sperm count as well as higher estradiol and total testosterone concentrations., What Is Known Already: Semen quality has declined during recent decades and has been negatively correlated with higher risks of common chronic diseases and mortality, highlighting its public health importance beyond fertility and reproduction. While most of the previous epidemiology literature on male fertility has focused on environmental exposures, dietary factors, and other related variables, little attention has been paid to occupational factors., Study Design, Size, Duration: This observational study included 377 men who were male partners in couples seeking infertility treatment at a fertility center, who enrolled in the Environment and Reproductive Health (EARTH) study between 2005 and 2019., Participants/materials, Setting, Methods: Self-reported information on lifting/moving heavy objects, typical shift, and physical level of exertion at work was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone concentrations. Linear regression models were used to evaluate the association between occupational factors and measures of testicular function, while adjusting for covariates such as age, BMI, education, race, smoking, and abstinence time, and accounting for multiple semen samples (mean = 2, min-max = 1-9) in analyses for semen parameters., Main Results and the Role of Chance: Men had a median (interquartile range) age of 36 (33, 39) years and were predominantly Caucasian (87%). Of the men who completed the survey, 12% reported often lifting or moving heavy objects at work, 6% reported heavy physical exertion at work, and 9% reported evening or rotating shifts. Men who reported often lifting or moving heavy objects at work had 46% higher sperm concentrations (P = 0.01) and 44% higher total counts (P = 0.01) compared with men who reported never lifting or moving heavy objects at work. Similar results were found for men working in rotating shifts compared to those in day shifts, as well as for men involved in heavy levels of physical exertion compared to those with light levels at work. We also found that men involved in heavy/moderate levels of physical exertion at work had higher circulating testosterone concentrations compared to those with lighter exertion (adjusted means of 515 and 427 ng/dl, respectively, P = 0.08), and men who often moved/lifted heavy objects at work had higher estradiol concentrations, compared to those who never did (adjusted means of 36.8 and 27.1 pg/ml, respectively, P = 0.07). Men working evening/rotating shifts had 24% higher testosterone (P = 0.04) and 45% higher estradiol concentrations (P = 0.01), compared to men working day shifts. No associations were observed for ejaculated volume, total motility, morphologically normal sperm, or serum FSH and LH concentrations., Limitations, Reasons for Caution: Due to our study design which recruited men from couples seeking fertility treatment, it may not be possible to generalize our findings to men from the general population. Also, as is the case of all studies based on self-reported questionnaires, measurement error and misclassification of the exposure are potential concerns., Wider Implications of the Findings: Physically demanding jobs and rotating or evening shift occupations may be associated with higher testicular function in men measured as higher sperm concentrations and counts as well as higher serum testosterone and estradiol levels. Confirmation of these findings in other non-fertility clinic study populations is warranted., Study Funding/competing Interest(s): NIH grants R01ES022955, R01ES009718, R01ES033651, and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and Legacy, Inc. R.A.G. works part time for Legacy, Inc., which provided funds to perform this analysis. There are no other conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study aimed to identify whether differences exist in postpartum depression (PPD) in US and Korean nurses and its related factors. Identifying occupational and personal factors that underlie potential differences will be helpful for women's occupational health., Methods: Baseline and postpartum survey data from employed nurses in the Korea Nurses' Health Study and Nurses' Health Study 3 (1244 Korean; 2742 US nurses) were analysed. Postpartum data collection was done via online survey. PPD was analysed based on cultural validation from prior studies using the Edinburgh Postnatal Depression Scale (cut-off of 10 for Korea and 13 for USA); depressive symptoms prior to pregnancy and childbirth, general characteristics and sleep satisfaction were also measured. Descriptive statistics, χ 2 tests and t-tests and multivariate ordinal logistic regression analysis were performed., Results: 45.9% of Korean participants had clinical symptoms of PPD (≥10), whereas US participants presented with 3.4% (≥13). Prior depressive symptoms were also higher in Korean participants (22.5%) compared with their US counterparts (4.5%). Prior depressive symptoms and poor sleep satisfaction were significant risk factors of PPD in both cohort groups, and vaginal birth was an additional influencing factor in Korean participants., Conclusions: Differences in PPD rates and related factors suggest the role of stress, cultural variation and differing work systems. Nurses and other women shift-workers noted to have depressive symptoms before and during pregnancy and exhibit PPD symptoms should especially be followed closely and offered supportive mental health services that include greater flexibility in returning to work., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Certain symptoms associated with infertility are associated with cardiovascular disease, including menstrual cycle irregularity, early menopause, and obesity; however, few studies have investigated the association between infertility and cardiovascular disease risk. Methods and Results Participants in the NHSII (Nurses' Health Study II) who reported infertility (12 months of trying to conceive without success, including women who subsequently conceived) or who were gravid, with no infertility were followed from 1989 until 2017 for development of incident, physician-diagnosed coronary heart disease (CHD) (myocardial infarction, coronary artery bypass grafting, angioplasty, stent) and stroke. Time-varying Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs and were adjusted a priori for potential confounding variables. Among 103 729 participants, 27.6% reported having ever experienced infertility. Compared with gravid women who had not reported infertility, women with a history of infertility had greater risk of CHD (HR, 1.13 [95% CI, 1.01-1.26]) but not stroke (HR, 0.91 [95% CI, 0.77-1.07]). The association between history of infertility and CHD was strongest among women who reported infertility at an earlier age (HR for infertility first reported at ≤25 years, 1.26 [95% CI, 1.09-1.46]; HR at 26-30 years, 1.08 [95% CI, 0.93-1.25]; HR at >30 years, 0.91 [95% CI, 0.70-1.19]). When we investigated specific infertility diagnoses, elevated risk of CHD was observed among women whose infertility was attributed to an ovulatory disorder (HR, 1.28 [95% CI, 1.05-1.55]) or endometriosis (HR, 1.42 [95% CI, 1.09-1.85]). Conclusions Women with infertility may be at an increased risk of CHD. Risk differed by age at first infertility diagnosis and was restricted to ovulatory- and endometriosis-related infertility.

Introduction: Supplements sold with claims to promote weight loss, cleansing/detoxing, increased energy, or boosted immunity can be dangerous, and consumers experiencing extreme stressors may be especially vulnerable to deceptive claims. The purpose of our study was to investigate associations of financial strain and psychological distress during the COVID-19 pandemic with use of supplements sold for weight loss, cleanse/detox, energy, or immunity., Methods: We used repeated-measures data gathered over five survey waves from April/May 2020-April 2021 from the COVID-19 Substudy ( N = 54,951), within three prospective US national cohorts (Nurses' Health Study 2, Nurses' Health Study 3, and Growing Up Today Study), to investigate longitudinal associations between financial strain and psychological distress and risk of use of potentially dangerous types of supplements. Surveys assessed use of supplements prior to and during the first year of the pandemic, as well as financial precarity, food insecurity, depressive and anxiety symptoms, perceived stress, and daily hassles. We fit sociodemographic-adjusted modified Poisson GEE models to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for associations between baseline or lagged time-varying predictors and prevalent or incident (i.e., new-onset) use of each supplement type., Results: At baseline in April/May 2020, soon after pandemic onset, current use of supplement types was: weight loss 2.7%; cleanse/detox 3.2%; energy 4.4%; immune 22.6%. By the end of the study period, cumulative incidence was: weight loss 3.5%; cleanse/detox 3.7%; energy 4.5%; immune 21.3%. In prevalent-use analyses, financial precarity, food insecurity, and psychological distress were associated with up to 2.4 times the risk of use of these types of supplements across the study period. Similarly, in incident-use analyses, financial precarity and psychological distress were associated with up to 2.1 times the risk of initiating use; whereas, high food insecurity was associated with nearly 1.8 times higher risk of onset of weight-loss supplements use but was not associated with onset of use of other types of supplements., Discussion: We found consistent evidence that during the first year of the pandemic, participants experiencing elevated financial strain and psychological distress were at heightened risk of initiating use of potentially dangerous types of supplements. Our findings raise concerns about deceptive claims about the safety and product effectiveness by manufacturers of these supplements to profit from vulnerable consumers during the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Austin, Beccia, Raffoul, Jackson, Sarda, Hart, Chavarro and Rich-Edwards.)

Importance: Few modifiable risk factors for post-COVID-19 condition (PCC) have been identified., Objective: To investigate the association between healthy lifestyle factors prior to SARS-CoV-2 infection and risk of PCC., Design, Setting, and Participants: In this prospective cohort study, 32 249 women in the Nurses' Health Study II cohort reported preinfection lifestyle habits in 2015 and 2017. Healthy lifestyle factors included healthy body mass index (BMI, 18.5-24.9; calculated as weight in kilograms divided by height in meters squared), never smoking, at least 150 minutes per week of moderate to vigorous physical activity, moderate alcohol intake (5 to 15 g/d), high diet quality (upper 40% of Alternate Healthy Eating Index-2010 score), and adequate sleep (7 to 9 h/d)., Main Outcomes and Measures: SARS-CoV-2 infection (confirmed by test) and PCC (at least 4 weeks of symptoms) were self-reported on 7 periodic surveys administered from April 2020 to November 2021. Among participants with SARS-CoV-2 infection, the relative risk (RR) of PCC in association with the number of healthy lifestyle factors (0 to 6) was estimated using Poisson regression and adjusting for demographic factors and comorbidities., Results: A total of 1981 women with a positive SARS-CoV-2 test over 19 months of follow-up were documented. Among those participants, mean age was 64.7 years (SD, 4.6; range, 55-75); 97.4% (n = 1929) were White; and 42.8% (n = 848) were active health care workers. Among these, 871 (44.0%) developed PCC. Healthy lifestyle was associated with lower risk of PCC in a dose-dependent manner. Compared with women without any healthy lifestyle factors, those with 5 to 6 had 49% lower risk (RR, 0.51; 95% CI, 0.33-0.78) of PCC. In a model mutually adjusted for all lifestyle factors, BMI and sleep were independently associated with risk of PCC (BMI, 18.5-24.9 vs others, RR, 0.85; 95% CI, 0.73-1.00, P = .046; sleep, 7-9 h/d vs others, RR, 0.83; 95% CI, 0.72-0.95, P = .008). If these associations were causal, 36.0% of PCC cases would have been prevented if all participants had 5 to 6 healthy lifestyle factors (population attributable risk percentage, 36.0%; 95% CI, 14.1%-52.7%). Results were comparable when PCC was defined as symptoms of at least 2-month duration or having ongoing symptoms at the time of PCC assessment., Conclusions and Relevance: In this prospective cohort study, pre-infection healthy lifestyle was associated with a substantially lower risk of PCC. Future research should investigate whether lifestyle interventions may reduce risk of developing PCC or mitigate symptoms among individuals with PCC or possibly other postinfection syndromes.

Objective: This study aimed to examine the association of antimüllerian hormone (AMH) with concurrent and prospective measures of adiposity during approximately 9 years of follow-up., Methods: Participants were 697 parous women from the Project Viva prebirth cohort without polycystic ovarian syndrome. We measured AMH at approximately 3 years postpartum (baseline). Outcomes were weight, body mass index (BMI), and waist circumference assessed at baseline, 4, and 9 years later; % body fat was assessed by bioimpedance at the 4- and 9-year visit. We used linear mixed-effect models including all outcome time points and accounting for age across follow-up and hormonal contraception prescription. In an additional model, we further adjusted for height., Results: Median AMH was 1.97 ng/mL (interquartile range, 0.83-4.36 ng/mL), 29.1% had AMH <1.0 ng/mL, and mean age at AMH measurement was 36.7 years (SD, 4.9 y; range, 20-48 y). AMH was inversely associated with average weight, BMI, and waist circumference over follow-up. In age-adjusted models, women with AMH <1.0 versus ≥1.0 ng/mL were 4.92 kg (95% CI, 2.01-7.82 kg) heavier, had a 2.51 cm (95% CI, 0.12-4.89 cm) greater waist circumference, and a 1.46 kg/m 2 (95% CI, 0.44-2.48 kg/m 2 ) greater BMI across the 9 years of follow-up. Findings were similar after covariate adjustment and when AMH was modeled continuously. AMH was also inversely associated with higher fat mass %; however, the CI crossed the null., Conclusion: Low AMH at baseline was associated with greater adiposity concurrently and across approximately 9 years of follow-up. Whether low AMH is a useful marker of metabolic risk across midlife requires further research., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2023 by The North American Menopause Society.)

Background: Only few longitudinal studies with high risk of bias have examined relationship between pets and adolescents' mental health., Methods: Our prospective cohort study followed depression-free US adolescents aged 12-18, enrolled in the Growing Up Today Study from pet ownership assessment in 1999 to possible occurrence of high depressive symptoms defined based on the McKnight Risk Factor Survey between 2001 and 2003. Propensity-score-adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using generalized estimating equation models., Results: Among 9631 adolescents [42.4 % male, mean age 14.9 years (SD 1.6)], we found no association between pet ownership and risk of high depressive symptoms (OR any&#95;pet  = 1.14; 95%CI, 0.95-1.38). Stratified analyses revealed no evidence of effect modification by sex, but effect modification by maternal history of depression (depressed mothers OR any&#95;pet  = 0.83; 95 % CI: 0.58-1.19, non-depressed mothers OR any&#95;pet  = 1.27; 95 % CI: 1.02-1.58; P intx  = 0.03), which differed further by children's sex. Effects were more pronounced among children with a history of childhood abuse (OR any&#95;pet  = 0.41 (0.14-1.15); P intx  ≤0.03). No major differences by type of pet owned were observed in any of these analyses., Limitations: Our sample is predominantly white and all are offspring of nurses with a similar academic background which could affect generalizability., Conclusions: Overall, we found no association between pet ownership and depression during adolescence, however subgroup analyses indicated some individuals may benefit from a pet. Future longitudinal studies with more detailed exposure assessments, including pet attachment are needed to further explore the potential of human-animal interaction on mental health., Competing Interests: Conflict of interest All authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To examine the association between consumption of fruits and vegetables and pesticide residue intake from consumption of fruits and vegetables and risk of ultrasound- or hysterectomy-confirmed fibroids. Only a few studies have evaluated the association of fruit and vegetable intake with uterine fibroids, with inconsistent results. No studies have examined pesticide exposure through fruits and vegetables with fibroid risk., Design: Prospective cohort study. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs)., Setting: Not applicable., Patient(s): A total of 81,782 premenopausal participants from the Nurses' Health Study II cohort were followed from 1991 to 2009 for fruit and vegetable analysis, and 49,927 participants were followed from 1999 to 2009 for pesticide residue burden analysis. Their diet was assessed every 4 years with a food frequency questionnaire. Fruits and vegetables were classified into high- or low-pesticide residues using a validated method based on surveillance data from the US Department of Agriculture., Intervention(s): Not applicable., Main Outcome Measure(s): Cases of ultrasound- or hysterectomy-confirmed fibroids were identified from self-reports to validated questionnaires., Result(s): From 1991 to 2009, 9,706 incident cases of ultrasound- or hysterectomy-confirmed fibroids were reported, and 4,195 incident cases were identified from 1999 to 2009. No association was observed between total fruit and vegetable consumption and uterine fibroid risk. Participants with the highest intake of total fruits (≥4/day) were 10% less likely to develop uterine fibroids compared with participants who consumed <1/day (95% CI = 0.80-1.01). No associations were observed with any other fruit or vegetable groups. An inverse association was observed between intake of high-pesticide-residue fruits and vegetables and fibroid risk (HR for 5 th vs. 1 st quintile = 0.87; 95% CI = 0.77-0.99), while no association with low-pesticide-residue fruits and vegetables was observed (HR for 5 th vs. 1 st quintile = 1.08; 95% CI = 0.95-1.23)., Conclusion(s): Our findings suggest that pesticide residues on fruits and vegetables are not associated with a higher risk of uterine fibroids. Furthermore, our results suggest that intake of fruits may be associated with a lower risk of fibroids. Future research in this area should focus on dietary exposures across the life course as well as assessment of class-specific pesticides., (Published by Elsevier Inc.)

Maternal mortality is unusually high in the United States compared to other wealthy nations and is characterized by major disparities in race/ethnicity, geography, and socioeconomic factors. Similar to other developed nations, the United States has seen a shift in the underlying causes of pregnancy-related death, with a relative increase in mortality resulting from diseases of the cardiovascular system and preexisting medical conditions. Improved continuity of care aimed at identifying reproductive-age women with preexisting conditions that may heighten the risk of maternal death, preconception management of risk factors for major adverse pregnancy outcomes, and primary care visits within the first year after delivery may offer opportunities to address gaps in medical care contributing to the unacceptable rates of maternal mortality in the United States.

Background: Females with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes mellitus (T2D) later in life., Objective: This study prospectively examined whether greater habitual coffee consumption was related to a lower risk of T2D among females with a history of GDM., Methods: We followed 4522 participants with a history of GDM in the NHS II for incident T2D between 1991 and 2017. Demographic, lifestyle factors including diet, and disease outcomes were updated every 2-4 y. Participants reported consumption of caffeinated and decaffeinated coffee on validated FFQs. Fasting blood samples were collected in 2012-2014 from a subset of participants free of diabetes to measure glucose metabolism biomarkers (HbA1c, insulin, C-peptide; n = 518). We used multivariable Cox regression models to calculate adjusted HRs and 95% CIs for the risk of T2D. We estimated the least squares mean of glucose metabolic biomarkers according to coffee consumption., Results: A total of 979 participants developed T2D. Caffeinated coffee consumption was inversely associated with the risk of T2D. Adjusted HR (95% CI) for ≤1 (nonzero), 2-3, and 4+ cups/d compared with 0 cup/d (reference) was 0.91 (0.78, 1.06), 0.83 (0.69, 1.01), and 0.46 (0.28, 0.76), respectively (P-trend = 0.004). Replacement of 1 serving/d of sugar-sweetened beverage and artificially sweetened beverage with 1 cup/d of caffeinated coffee was associated with a 17% (risk ratio [RR] = 0.83, 95% CI: 0.75, 0.93) and 9% (RR = 0.91, 95% CI: 0.84, 0.99) lower risk of T2D, respectively. Greater caffeinated coffee consumption was associated with lower fasting insulin and C-peptide concentrations (all P-trend <0.05). Decaffeinated coffee intake was not significantly related to T2D but was inversely associated with C-peptide concentrations (P-trend = 0.003)., Conclusions: Among predominantly Caucasian females with a history of GDM, greater consumption of caffeinated coffee was associated with a lower risk of T2D and a more favorable metabolic profile., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk; cis 20:2n-6 was associated with follicular lymphoma risk (OR [95% CI] per one standard deviation increase: 1.35 [1.03-1.77]), and the omega-6/omega-3 PUFA ratio was associated with diffuse large B-cell lymphoma risk (2.33 [1.23-4.43]). Overall, PUFA did not demonstrate a role in NHL etiology; the two unexpected positive associations lack clear biologic explanations.

Purpose: To investigate whether history of comorbidities is associated with markers of ovarian reserve among subfertile women., Methods: This observational study includes 645 women seeking fertility care at the Massachusetts General Hospital who enrolled in the Environment and Reproductive Health (EARTH) study (2005-2019). Women completed a comprehensive questionnaire including medical diagnosis of comorbidities. Ovarian reserve markers including antral follicle count (AFC), assessed by transvaginal ultrasound, and circulating serum levels of day 3 FSH and AMH, are assessed by immunoassays. We fit linear regression models to evaluate the association between history of comorbidities and markers of ovarian reserve while adjusting for confounders., Results: Self-reported history of hypertension, cancer, and neurological disorders was negatively associated with AFC in unadjusted models and in adjusted models for age, smoking, physical activity, comorbidity count, and BMI. Adjusted mean AFC (95% CI) was lower among women with history of hypertension, compared to women with no self-reported history of hypertension (11.5 vs 15.6, p value 0.0001). In contrast, day 3 FSH levels were positively related to history of eating disorders in both unadjusted and adjusted models (10.8 vs. 7.43 IU/L, p value ≤ 0.0001). Self-reported history of other comorbidities was unrelated to AFC, day 3 FSH, and AMH levels., Conclusions: History of hypertension, cancer, and neurological disorders was negatively associated with AFC, and eating disorders were positively related to day 3 FSH levels. The prevention of common comorbidities among women in reproductive age may help increase women's fertility given the declining birth rates and increasing use of assisted reproductive technologies in the past years., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate barriers in accessing care for infertility in Mexico, because little is known about this issue for low and middle-income countries, which comprise 80% of the world's population., Design: Cross-sectional analysis., Setting: Mexcian Teachers' Cohort., Patients: A total of 115,315 female public school teachers from 12 states in Mexico., Interventions: None., Main Outcome Measures: The participants were asked detailed questions about their demographics, lifestyle characteristics, access to the health care system, and infertility history via a self-reported questionnaire. Log-binomial models, adjusted a priori for potential confounding factors, were used to estimate the prevalence ratios (PRs) and 95% confidence intervals ( CIs) of accessing medical care for infertility among women reporting a history of infertility., Results: A total of 19,580 (17%) participants reported a history of infertility. Of those who experienced infertility, 12,470 (63.7%) reported seeking medical care for infertility, among whom 8,467 (67.9%) reported undergoing fertility treatments. Among women who reported a history of infertility, women who taught in a rural school (PR, 0.95; 95% CI, 0.92-0.97), spoke an indigenous language (PR, 0.88; 95% CI, 0.84-0.92), or had less than a university degree (PR, 0.93; 95% CI, 0.90-0.97) were less likely to access medical care for fertility. Women who had ever had a mammogram (PR, 1.07; 95% CI, 1.05-1.10), had a pap smear in the past year (PR, 1.08; 95% CI, 1.06-1.10), or who had used private health care regularly or in times of illness were more likely to access medical care for fertility., Conclusions: The usage of infertility care varied by demographic, lifestyle, and access characteristics, including speaking an indigenous language, teaching in a rural school, and having a private health care provider., (© 2022 The Authors.)

Objective: To examine the association between the intake of fruits and vegetables with high- vs. low-pesticide residue burden and diagnosis of laparoscopically confirmed endometriosis. The etiology of endometriosis is not well understood, but dietary factors may influence the risk. Pesticides may act as endocrine disruptors, and the intake of pesticide-contaminated food is a common exposure pathway., Design: Prospective cohort study. Hazard ratios and 95% confidence intervals were calculated using multivariable Cox proportional hazard models to evaluate the intake of fruits and vegetables with high- and low-pesticide residues in relation to the diagnosis of laparoscopically confirmed endometriosis., Setting: Not applicable., Patient(s): Premenopausal US women (N = 52,053) of the Nurses' Health Study II, aged 34-53 years at study baseline (1999), were followed until 2013. The diet was assessed every 4 years using a validated food frequency questionnaire. A previously developed and validated pesticide residue burden score (PRBS), on the basis of the US Department of Agriculture Pesticide Data Program, was used to assign fruits and vegetables to pesticide residue groups (high/low)., Intervention(s): Not applicable., Main Outcome Measure(s): Cases of laparoscopically confirmed endometriosis were identified from self-reports to validated questionnaires., Result(s): During 14 years of follow-up, 956 incidences of laparoscopically confirmed endometriosis were reported. No association was observed between the intake of high- or low-PRBS fruit and vegetable intake and endometriosis (hazard ratio for 5th vs. 1st quintile: high-PRBS intake = 0.94, 95% confidence interval = 0.73-1.23; low-PRBS intake = 1.07, 95% confidence interval = 0.82-1.40). No associations were observed for high- or low-PRBS fruit and vegetable intake by fertility status., Conclusion(s): No clear associations were observed between high- or low-PRBS fruit and vegetable intake and endometriosis risk among premenopausal women. To our knowledge, this is the first study to evaluate the association between dietary pesticide residue intake and endometriosis. Further research is needed, particularly to evaluate this association among a younger population of women (adolescence or early adulthood) and assess the dietary exposure to specific pesticides or chemical families., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: We examined longitudinal associations of psychosocial stressors with menopausal symptoms and well-being of women in midlife in a longitudinal cohort., Methods: This study is based on 682 women from Project Viva, a prospective cohort enrolled in 1999 to 2002 during pregnancy (median age = 33.3 y) and followed for almost two decades. In pregnancy, women self-reported psychosocial stressors (history of physical and sexual abuse and financial instability, from childhood to the current pregnancy). In 2017 to 2021 (median age, 51.6 y), they reported their menopausal symptoms (0-44 point scale) and well-being (general health [good/fair/poor vs excellent/very good], generalized anxiety symptoms, and depressive symptoms [both-more than minimal levels vs none/minimal]). We performed multivariable and logistic regression models to examine associations of psychosocial stressors with outcomes, adjusting for covariates., Results: History of physical abuse (reported by 37.3%) was associated with worse menopausal symptoms in the somatovegetative (odds ratio [OR], 0.46 points; 95% confidence interval [CI], 0.04-0.87 points) and psychological (OR, 0.52 points; 95% CI, 0.07-0.97 points) domains and with worse general health (OR, 1.73; 95% CI, 1.17-2.55) and greater depressive symptoms (OR, 1.74; 95% CI, 1.05-2.87). History of sexual abuse (7.7%) was associated with worse menopausal symptoms (OR, 2.81 points; 95% CI, 1.05-4.56) and worse general health (OR, 2.04; 95% CI, 1.04-4.03) but not with depressive symptoms. History of financial instability (10.8%) was associated with worse menopausal symptoms (1.92 points; 0.49 to 3.34), worse general health (OR, 2.16; 95% CI, 1.24-3.75), and greater depressive symptoms (OR, 2.68; 95% CI, 1.44-4.98). We observed no association between psychosocial stressors and generalized anxiety symptoms assessed at midlife., Conclusions: Psychosocial stressors were associated with worse menopausal symptoms and well-being decades after initial report., Competing Interests: Financial disclosure/conflicts of interest: H.J. reports the following relationships (over the past 12 months): grant support from National Institutes of Health, Merck, Pfizer. Consultant and advisory fees from Eisai, Jazz, Bayer. Funding to institution from NeRRe/KANDy, Que-Oncology. Spouse is an employee of Arsenal Biosciences; Spouse has an equity stake in Merck Research Labs and Tango Therapeutics. E.O. receives funding from UpToDate. The other authors have nothing to disclose., (Copyright © 2022 by The North American Menopause Society.)