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Objectives: To better understand whether history of infertility is associated with anti-Müllerian hormone (AMH) levels later in life, outside of reproduction., Methods: Among 1,758 premenopausal women in the Nurses' Health Study II with measured AMH, we used multivariable generalized linear models to compare log-transformed plasma AMH for women with a history of infertility compared with fertile women. We investigated AMH levels by cause of infertility and effect modification by menstrual cycle regularity. Lastly, we investigated AMH levels by history of primary and secondary infertility and age at reported infertility., Results: Mean age at blood collection was 40 years. We observed no association between overall history of infertility and AMH levels (% difference AMH: -8.1% [CI, -19.4 to 4.8]). The association between overall infertility and AMH was strongest among women who first reported infertility at >30 years (-17.7% [CI, -32.1 to -0.3])., Conclusions: Overall, we observed no association between the history of infertility and AMH levels later in life. However, specific subgroups of women with a history of infertility may have lower AMH levels throughout life compared with fertile women. This association was observed among subgroups, such as those who first experienced infertility at >30 years. These findings have implications for mechanisms through which infertility may be associated with premature menopause and chronic disease risk., Competing Interests: Financial disclosure/conflicts of interest: S.A.M. receives ongoing institutional funding from the Department of Defense, Abbvie (grant), and Marriot Family Foundation (grant). She also receives honoraria from University of British Columbia, WERF, Huilun Shanghai, and University of Kansas Medical Center (honoraria). She receives coverage for travel to meetings by SRI, ESHRE, University of Michigan, Massachusetts Institute of Technology, ASRM, LIDEA Registry, Taiwan Endometriosis Society, SEUD, Japan Endometriosis Society, and NASEM. She receives personal fees for advisory board, roundtable, consultant, or editor role from AbbVie, Roche, Frontiers in Reproductive Health, Abbott, and LIDEA Registry. She holds unpaid board or leadership roles at Human Reproduction, SWHR, WERF, WES, ASRM, ESHRE. The other authors have nothing to disclose., (Copyright © 2024 by The Menopause Society.)

Objective: To assess whether infants born to women with a history of recurrent pregnancy loss (RPL) have an increased risk of adverse perinatal outcomes following frozen embryo transfer (FET) compared to women without a history of infertility or RPL., Design: Retrospective cohort study utilizing the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) database between 2014 and 2020., Subjects: Patients in the SART CORS database who underwent their first FET resulting in live birth either with a diagnosis of RPL (cases n=3,299) or without a history of RPL or infertility, the comparison population being tubal ligation (TL) only (n=1408)., Exposure: Recurrent pregnancy loss MAIN OUTCOME: Low birthweight (<2500g), additional outcomes included gestational age (continuous), birthweight (continuous), preterm delivery (< 37 weeks), mode of delivery, and neonatal death, defined as death prior to the completion of the 28 th day of life., Results: We observed no statistically significant difference in low birthweight, birthweight overall, mode of delivery or risk of neonatal death between patients with RPL compared to women with tubal ligation who underwent their first FET resulting in live birth. Patients with history of RPL compared to TL utilizing FET were more likely to have a later gestational age at delivery (p<0.001). Patients with RPL were also less likely to have a preterm delivery (imputed AOR 0.75 [0.64, 0.89]) than the TL patients. Furthermore, performing preimplantation genetic testing for aneuploidy (PGTA) in both patients with recurrent pregnancy loss or tubal ligation did not impact perinatal outcomes compared to patients who did not undergo PGTA., Conclusions: Patients with history of recurrent pregnancy loss do not have an increased risk of adverse perinatal outcomes when they undergo FET compared to patients without infertility or recurrent pregnancy loss. In addition, performing IVF/PGTA in patients with RPL does not adversely impact birth outcomes of their infants., (Copyright © 2024. Published by Elsevier Inc.)

Background: Women who reach menarche and menopause at earlier ages have been shown to be at increased risk for numerous conditions including cardiovascular disease, cancer, depression, and obesity; however, risk factors for earlier ages of menarche and menopause are not fully understood. Therefore, we aimed to perform a retrospective investigation of the associations between a personal birthweight and/or being born preterm and the age of and menarche and menopause and related events in the Women's Health Initiative, a large, racially and ethnically diverse cohort of postmenopausal women., Methods: At study entry, women reported their birthweight by category (< 6 lbs., 6-7 lbs. 15 oz, 8-9 lbs. 15 oz, or ≥ 10 lbs.) and preterm birth status (4 or more weeks premature). Ages at events related to menarche and menopause were also self-reported. Linear regression and logistic regression models were used to estimate unadjusted and adjusted effect estimates (β) and odds ratios (OR), respectively (n ≤ 86,857). Individuals born preterm were excluded from all birthweight analyses., Results: After adjustments, individuals born weighing < 6lbs. were more likely to reach natural menopause at an earlier age (adjusted β=-0.361, SE = 0.09, P = < 0.001) and have a shorter reproductive window (adjusted β = -0.287, SE = 0.10, p < 0.004) compared to individuals weighing 6-7 lbs. 15 oz. Individuals born preterm were also more likely to reach natural menopause at an earlier age (adjusted β=-0.506, SE = 0.16, P = 0.001) and have a shorter reproductive window (adjusted β = -0.418, SE = 0.17, p < 0.006)., Conclusions: These findings raise concerns that, as more preterm and low birthweight individuals survive to adulthood, the prevalence of earlier-onset menarche and menopause may increase. Clinical counseling and interventions aimed at reducing the incidence of preterm and low birthweight births, as well as intensification of lifestyle modifications to reduce CVD risk among women with these early-life risk factors, should be prioritized., (© 2024. The Author(s).)

Background: Although endometriosis is a common condition-affecting ∼10% of premenopausal individuals-its etiology is unknown. Diet receives a lot of attention from patients, but studies of the role of diet are limited. Examining dietary patterns is essential to provide new insight., Objective: We sought to determine whether dietary patterns are associated with laparoscopically-confirmed endometriosis diagnosis., Study Design: We conducted a prospective cohort study among 81,997 premenopausal participants of the Nurses' Health Study II, who were followed from 1991-2015. Diet was assessed with validated food frequency questionnaires every 4 years. We examined 6 dietary patterns: Western, Prudent, Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an estrogen-associated pattern, and a proinflammatory pattern. Cox proportional hazard ratios and 95% confidence intervals were used to quantify the association between each of these patterns and laparoscopically-confirmed endometriosis diagnosis., Results: Three thousand eight hundred ten incident cases of endometriosis were diagnosed during 24 years of follow-up. Adherence to the Alternative Healthy Eating Index, reflecting a healthier dietary pattern, was associated with a 13% lower risk of endometriosis diagnosis (fifth vs first quintile 95% confidence interval, 0.78-0.96; P trend =.02). Participants in the highest quintile of the Western dietary pattern, characterized by high intake of red meat, processed meat, refined grains, and desserts, had a 27% higher risk of endometriosis diagnosis than those in the lowest quintile (95% confidence interval, 1.09-1.47; P trend =.004). The Prudent, Dietary Approaches to Stop Hypertension, and estrogen-associated dietary patterns did not demonstrate clear associations with endometriosis risk, and there was the suggestion of a higher risk of endometriosis diagnosis among those with a higher proinflammatory diet score (hazard ratio for fifth vs first quintile, 1.10 [95% confidence interval, 0.99-1.23]; P trend =.01)., Conclusion: Our results suggest that consuming a dietary pattern that adheres to the Alternative Healthy Eating Index-2010 recommendations lowers the risk of endometriosis diagnosis, potentially through a beneficial impact on pelvic pain. In addition, consuming a less healthy diet high in red/processed meats and refined grains may have a detrimental impact on endometriosis symptoms., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Loreto, in the Peruvian Amazon, has one of the highest adolescent pregnancy rates in the country. However, underlying causes of adolescent pregnancy are not fully understood as data are limited in Indigenous and remote Amazonian communities. This study investigated adolescent reproductive health within Loreto using an ecological systems framework. Forty-one semi-structured interviews were conducted in June 2022: community leaders ( n  = 12) and adolescent participants between 15 and 17 years of age (pregnant girls, n  = 11; never pregnant girls, n  = 9; and boys, n  = 9). We also conducted focus group discussions with community health workers and educators in October 2022 (three focus groups, n  = 15). Adolescent reproductive health is complex with multi-layered factors that put girls at higher risk of pregnancy. We found a paradoxical relationship between expected social and gender norms and individual desires. This research provides a contextual understanding of the lived experience of adolescents and young people in the Amazon region of Peru. Our findings suggest the need for greater exploration of the contradictory ideas surrounding adolescent pregnancy and female sexuality.

Background: Several studies have suggested an association between infertility and risk of endometrial cancer. However, most studies have evaluated this relationship in premenopausal people, yet the mean age of endometrial cancer is 60 years old, after the average age of menopause., Methods: Our study included Women's Health Initiative participants who self-reported whether they had a history of infertility. Cox proportional hazards models were used to examine the association between infertility and incident endometrial cancer. Given that all infertility diagnoses occurred prior to study enrollment, we conducted secondary analyses using logistic regression examining prevalent endometrial cancer cases diagnosed before study baseline., Results: Approximately 18% of participants reported a history of infertility. No statistically significant association was observed between infertility and risk of incident endometrial cancer overall (incident cases=1622; hazard ratio [HR]=1.12; 95% confidence interval [CI]=0.99-1.26). While point estimates suggested an increase in risk of endometrial cancer among women with BMI ≥25 (HR=1.15; 95% CI=0.99-1.33), none of the associations were statistically significant. There was an association between history of infertility and prevalent endometrial cancer cases (odds ratio [OR]=1.19; 95% CI=1.06-1.34), with the strongest association for infertility diagnosis due to endometriosis (OR=2.42; 95% CI=1.83-3.19)., Conclusions: In a population of postmenopausal participants, we observed a modest, but not statistically significant, association between overall infertility and incident endometrial cancer, with the suggestion of a higher risk among those with a BMI ≥25., Impact: Our findings highlight, as observed in previous studies, that risk factors for endometrial cancer may vary by body mass index.

Purpose: Hysterectomy is associated with subsequent changes in circulating hormone levels, but the evidence of an association for tubal ligation is unclear. We evaluated whether circulating concentrations of androgens and estrogens differ by tubal ligation or hysterectomy status in postmenopausal women from the Women's Health Initiative (WHI)-Observational Study (OS)., Methods: Serum androgens and estrogens were measured in 920 postmenopausal women who did not use menopausal hormone therapy at the time of blood draw, of whom 139 self-reported a history of tubal ligation and 102 reported hysterectomy (with intact ovaries). Geometric mean hormone concentrations (GMs) and 95% confidence intervals (CIs) associated with a history of tubal ligation or hysterectomy (ever/never), as well as time since procedures, were estimated using adjusted linear regression with inverse probability of sampling weights to account for selection., Results: Circulating levels of 12 androgen/androgen metabolites and 20 estrogen/estrogen metabolites did not differ by tubal ligation status. Among women reporting prior hysterectomy compared to women without hysterectomy, we observed lower levels of several androgens (e.g., testosterone (nmol/L): GM yes 0.46 [95% CI:0.37-0.57] vs. GM no 0.62 [95% CI:0.53-0.72]) and higher levels of estrogen metabolites, for example, 2-hydroxyestrone-3-methyl ether (GM yes 11.1 [95% CI:8.95-13.9] pmol/L vs. GM no 8.70 [95% CI:7.38-10.3]) and 4-methoxyestrone (GM yes 6.50 [95% CI:5.05-8.37] vs. GM no 4.92 [95% CI:4.00-6.05])., Conclusion: While we did not observe associations between prior tubal ligation and postmenopausal circulating hormone levels, our findings support that prior hysterectomy was associated with lower circulating testosterone levels and higher levels of some estrogen metabolites, which may have implications for future hormone-related disease risks., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Importance: Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described., Objective: To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype., Design, Setting, and Participants: Population-based cohort study using data from the Utah Population Database. The cohort was assembled by matching 78 893 women with endometriosis in a 1:5 ratio to women without endometriosis., Exposures: Endometriosis cases were identified via electronic health records and categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other., Main Outcomes and Measures: Estimated adjusted hazard ratios (aHRs), adjusted risk differences (aRDs) per 10 000 women, and 95% CIs for overall ovarian cancer, type I ovarian cancer, and type II ovarian cancer comparing women with each type of endometriosis with women without endometriosis. Models accounted for sociodemographic factors, reproductive history, and past gynecologic operations., Results: In this Utah-based cohort, the mean (SD) age at first endometriosis diagnosis was 36 (10) years. There were 597 women with ovarian cancer. Ovarian cancer risk was higher among women with endometriosis compared with women without endometriosis (aHR, 4.20 [95% CI, 3.59-4.91]; aRD, 9.90 [95% CI, 7.22-12.57]), and risk of type I ovarian cancer was especially high (aHR, 7.48 [95% CI, 5.80-9.65]; aRD, 7.53 [95% CI, 5.46-9.61]). Ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR, 9.66 [95% CI, 7.77-12.00]; aRD, 26.71 [95% CI, 20.01-33.41]), type I ovarian cancer (aHR, 18.96 [95% CI, 13.78-26.08]; aRD, 19.57 [95% CI, 13.80-25.35]), and type II ovarian cancer (aHR, 3.72 [95% CI, 2.31-5.98]; aRD, 2.42 [95% CI, -0.01 to 4.85])., Conclusions and Relevance: Ovarian cancer risk was markedly increased among women with ovarian endometriomas and/or deep infiltrating endometriosis. This population may benefit from counseling regarding ovarian cancer risk and prevention and could be an important population for targeted screening and prevention studies.

Study Question: What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women?, Summary Answer: Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity., What Is Known Already: Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI., Study Design, Size, Duration: This study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis., Participants/materials, Setting, Methods: Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI., Main Results and the Role of Chance: Women who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies., Limitations, Reasons for Caution: The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics., Wider Implications of the Findings: This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention., Study Funding/competing Interest(s): HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: There has been limited prior research on the association between infertility and risk of colorectal cancer., Methods: Data from postmenopausal women in the Women's Health Initiative were used to estimate the association between self-reported infertility (12 months of trying to get pregnant without achieving a pregnancy) and the risk of colorectal cancer using Cox proportional hazard models., Results: No association was observed between infertility and risk of postmenopausal colorectal cancer [RR, 0.97; 95% confidence interval (CI), 0.87-1.08], invasive colorectal cancer (RR, 0.99; 95% CI, 0.88-1.10), or colorectal cancer mortality (RR, 0.89; 95% CI, 0.71-1.12)., Conclusions: Infertility was not found to be associated with colorectal cancer risk among postmenopausal women. Risk did not vary by specific infertility diagnoses., Impact: Infertility may not be associated with colorectal cancer risk., (©2024 American Association for Cancer Research.)

Background: Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient's quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP., Methods: Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2., Results: Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺., Conclusions: Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain., (© 2024. The Author(s).)

Objectives: Optimal postpartum care promotes healthcare utilization and outcomes. This qualitative study investigated the experiences and perceived needs for postpartum care among women in rural communities in Arizona, United States., Methods: We conducted in-depth interviews with thirty childbearing women and analyzed the transcripts using reflexive thematic analysis to gauge their experiences, needs, and factors affecting postpartum healthcare utilization., Results: Experiences during childbirth and multiple structural factors, including transportation, childcare services, financial constraints, and social support, played crucial roles in postpartum care utilization for childbearing people in rural communities. Access to comprehensive health information and community-level support systems were perceived as critical for optimizing postpartum care and utilization., Conclusions for Practice: This study provides valuable insights for policymakers, healthcare providers, and community stakeholders in enhancing postpartum care services for individuals in rural communities in the United States., (© 2024. The Author(s).)

Purpose: Although infertility (i.e., failure to conceive after ≥ 12 months of trying) is strongly correlated with established breast cancer risk factors (e.g., nulliparity, number of pregnancies, and age at first pregnancy), its association with breast cancer incidence is not fully understood. Previous studies were primarily small clinic-based or registry studies with short follow-up and predominantly focused on premenopausal breast cancer. The objective of this study was to assess the relationship between infertility and postmenopausal breast cancer risk among participants in the Women's Health Initiative (analytic sample = 131,784; > 25 years of follow-up)., Methods: At study entry, participants were asked about their pregnancy history, infertility history, and diagnosed reasons for infertility. Incident breast cancers were self-reported with adjudication by trained physicians reviewing medical records. Cox proportional hazards models were used to estimate risk of incident postmenopausal breast cancer for women with infertility (overall and specific infertility diagnoses) compared to parous women with no history of infertility. We examined mediation of these associations by parity, age at first term pregnancy, postmenopausal hormone therapy use at baseline, age at menopause, breastfeeding, and oophorectomy., Results: We observed a modest association between infertility (n = 23,406) and risk of postmenopausal breast cancer (HR = 1.07; 95% CI 1.02-1.13). The association was largely mediated by age at first term pregnancy (natural indirect effect: 46.4% mediated, CI 12.2-84.3%)., Conclusion: These findings suggest that infertility may be modestly associated with future risk of postmenopausal breast cancer due to age at first pregnancy and highlight the importance of incorporating reproductive history across the life course into breast cancer analyses., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Anti-Müllerian hormone is a reliable measure of ovarian reserve associated with menopause timing and fertility. Previous studies have observed that individuals with endometriosis have lower anti-Müllerian hormone levels than those without. However, sample sizes have been small and information is limited regarding the long-term influence of endometriosis on anti-Müllerian hormone levels among the general population, which may have important implications for menopause timing and chronic disease risk., Methods: Among 1961 premenopausal women in the Nurses' Health Study II who provided a blood sample and had not been pregnant in the last 6 months, we used generalized linear models to determine the association between laparoscopically-confirmed endometriosis and log-transformed plasma anti-Müllerian hormone level, adjusted for age (continuous and squared) and other potential confounding variables., Results: Participants were on average 40 years old (interquartile range 37-42 years) at blood draw. Women with endometriosis diagnosed prior to blood draw (n = 119) had a lower mean anti-Müllerian hormone level (1.6 ng/mL [SD = 2.3]) than women without known endometriosis (n = 1842) (2.8 ng/mL [SD = 3.0]). In multivariable adjusted models, women with endometriosis had 29.6 % lower anti-Müllerian hormone levels (95 % CI: -45.4, -9.2 %) than women without. This association was greater among women with a body mass index of 25 kg/m 2 or more (percent difference: -44.0 % (-63.7, -13.8)), compared to those with a body mass index of under 25 kg/m 2 (percent difference: -19.8 % (-41.7, 10.4)), but did not vary by parity or infertility history., Conclusions: Lower anti-Müllerian hormone levels in women with endometriosis may be one mechanism through which endometriosis influences risk of infertility, younger age at menopause, and cardiovascular disease., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to COVID-19, schools were closed to mitigate disease spread. Past studies have shown that disruptions in education have unintended consequences for adolescents, including increasing their risk of school dropout, exploitation, gender-based violence, pregnancy and early unions. In Peru, the government closed schools from March 2020 to March 2022, declaring a national emergency that affected an estimated 8 million children. These closures may have unintended consequences, including increased adolescent pregnancy, particularly in Peru's rural, largely indigenous regions. Loreto, located in the Peruvian Amazon, has one of the highest adolescent pregnancy rates in the country and poor maternal and child health outcomes. The underlying causes may not be fully understood as data are limited, especially as we transition out of the pandemic. This qualitative study investigated the downstream effects of COVID-19 on adolescent education and reproductive health in Loreto's districts of Nauta and Parinari. In-depth interviews (n=41) were conducted with adolescents and community leaders. These were held in June 2022, 3 months after the reinstitution of in-person classes throughout Peru. Focus group discussions (FGDs) were also completed with community health workers and educators from the same study area in October 2022 to supplement our findings (3 FGDs, n=15). We observed that the economic, educational and health effects of the COVID-19 pandemic contributed to reduced contraceptive use, and increased school abandonment, early unions and adolescent pregnancy. The interplay between adolescent pregnancy and both early unions and school abandonment was bidirectional, with each acting as both a cause and consequence of the other., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Evidence continues to accumulate on the influence of the menstrual phase on several biobehavioral outcomes (e.g., substance misuse). Expansion of this knowledge is limited due to the burdensomeness of accurate menstrual phase assessment. Thus, we sought to create and validate a questionnaire that can be used as a stand-alone item within low-resource settings and numerous study designs (e.g., cross-sectional) to accurately identify both the follicular phase (FP) and the luteal phase (LP). Participants completed the self-administered four-item Menstrual Phase Identification Questionnaire (MPIQ) in two recently completed clinical trials. We assessed the accuracy of two MPIQ scoring criteria (less restrictive and more restrictive), as compared to self-report of onset of menses alone, with progesterone confirmation via dried blood spots. Participants ( n = 59) were, on average, 33.7 (standard deviation [ SD ]: ± 4.3) years old and provided a total of 83 responses. Assessing FP and LP using the self-reported onset of menses alone classified 65.1% of the responses with an overall phase identification accuracy of 60.2%. While the more restrictive MPIQ scoring classified 100% of the responses, it yielded a similar accuracy (68.4%). In contrast, the less restrictive MPIQ scoring classified 100% of the responses and also significantly improved phase identification accuracy to 92.1% ( p < .001). The MPIQ, as a stand-alone item, allows all cross-sectional responses to be classified with a high level of accuracy. This low-burden questionnaire can be used alone to identify FP and LP in studies that may be otherwise limited by study design, finances, and/or participant burden. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: Postpartum Medicaid eligibility extensions may increase access to healthcare for low-income women. However, its implications for healthcare utilization are unknown., Methods: We analyzed the linked-infant birth certificate and claims data of women whose childbirths were paid for by Medicaid between 2016 and 2019 in Arizona, United States. We evaluated associations between postpartum care visits and Medicaid insurance type and assessed effect modification by the delivery route and type of residence., Results: Women with pregnancy-related Medicaid insurance were less likely to attend postpartum visits, with an adjusted odds ratio (aOR) of 0.70 and a 95% confidence interval (CI) of 0.66 to 0.74 than those with continuous Medicaid insurance. Younger age, rural residence [aOR 0.83, CI 0.78, 0.88], vaginal delivery route [aOR 0.11, CI 0.10, 0.12], and the absence of complications during/after childbirth [aOR 0.58, CI 0.49, 0.70] were associated with the absence of postpartum care visit. Low-income women who lost their pregnancy-related Medicaid coverage after 60 days in Arizona experienced lower rates of postpartum care utilization., Discussion: Interventions to improve postpartum utilization should be considered beyond extending postpartum Medicaid coverage for low-income women., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Okechukwu, Abraham, Okechukwu, Magrath, Marrero, Farland and Alaofe.)

Background: Vaccinations against SARS-CoV-2 have consistently been shown to reduce the risk of severe COVID-19 disease. However, uptake of boosters has stalled in the United States at less than 20% of the eligible population. The objective of this study was to assess the reasons for not having obtained a bivalent booster within an existing COVID-19 cohort., Methods: A total of 2196 adult participants from the Arizona CoVHORT, a population-based cohort in the United States established in May 2020, who had received at least one dose of the COVID-19 vaccine, responded to surveys administered between February 13 and March 29, 2023 querying receipt of a bivalent booster and if not, the reasons for not receiving it. Descriptive statistics were employed, including frequencies of responses by participant characteristics, and multivariable logistic regression was used to assess the association between participant characteristics and selected themes for not having received the bivalent booster., Results: The most commonly reported reason for not having been boosted was a prior SARS-CoV-2 infection (39.5%), followed by concern about vaccine side effects (31.5%), believing that the booster would not provide additional protection over the vaccines already received (28.6%), and concern about booster safety (23.4%) or that it would not protect from SARS-CoV-2 infection (23.1%). For themes related to reasons for not having been boosted, those 60 years of age or older were less likely to select items related to knowledge (OR: 0.24; 95% CI: 0.11-0.55) or logistical concerns (OR: 0.09; 95% CI: 0.03-0.30) about the vaccine; while those reporting Hispanic ethnicity were more likely to convey concerns about logistics than those reporting non-Hispanic ethnicity (OR: 2.15; 95% CI: 1.08-4.30). Finally, compared to college graduates, those with some college or technical school were significantly more likely to select items related to the risks and benefits of the bivalent vaccine not being clear as reasons for not having been boosted (OR: 2.41; 95% CI: 1.69-3.43)., Conclusions: Improvement in booster uptake is necessary for optimal public health in the United States. The development of vaccines against SARS-CoV-2 occurred at an unprecedented speed, but vaccine uptake remains among the greatest current public health challenges as updated boosters continue to be developed and made available to the public. Interventions to improve vaccination rates require a variety of approaches., 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. Published by Elsevier Ltd.)

Purpose: To evaluate differences in health characteristics and birth outcomes for participants of a prenatal education and support program for pregnant teens, "Starting Out Right" (SOR) compared to nonparticipant pregnant teens in Pima, Maricopa, and Gila counties in Arizona to gauge benefits of program participation., Description: The SOR program is a community education and support program for pregnant teens based on a structured curriculum. All pregnant teens living in the service area are eligible to participate., Assessment: Vital statistics birth data from 2014 to 2019 were obtained from three counties in Arizona that identified SOR and non-SOR program participants. Logistic regression was used to calculate multivariable -adjusted odds ratios (aOR) for specific health characteristics (smoking, hypertensive disorders, overweight and obesity, gestational diabetes, sexually transmitted infections) and birth outcomes (C-section, preterm birth, NICU admission, birthweight, and breastfeeding) for SOR participants compared with nonparticipants. Variables in the adjusted models included age, BMI, smoking, gestational diabetes, race, ethnicity, county, WIC participation, insurance type, plurality, and month and year prenatal care began., Conclusion: These results suggest that participation in SOR was associated (p ≤ 0.06) with a reduced odds for low birthweight [aOR 0.7(95% CI 0.5,1.0)] and increased odds (p ≤ 0.05) of breastfeeding [aOR 1.3(95% CI 1.0,1.7)] compared to nonparticipants. These results provide evidence that the education components in the SOR program support improved pregnancy and breastfeeding outcomes for pregnant teens., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Advancements in medical technology and pharmacologic interventions have drastically improved survival of infants born preterm and low birth weight, but knowledge regarding the long-term health impacts of these individuals is limited and inconsistent., Aim: To investigate whether an individual's birthweight or history of being born preterm increases the risk of an adverse reproductive outcome., Study Design: Nested case-control study within the Women's Health Initiative., Subjects: 79,934 individuals who self-reported their personal birthweight category and/or preterm birth status., Outcomes Measures: Self-reported pregnancy outcomes: subfertility, miscarriage, stillbirth, preeclampsia, gestational diabetes, gestational hypertension, preterm birth, low birthweight infant, high birthweight infant. Logistic regression models were used to estimate unadjusted and adjusted odds ratios (OR)., Results: After adjustments, individuals reporting their birthweight <6lbs. were 20 % more likely to have a stillbirth or 70 % more likely to have a low birthweight infant and were less likely to have a full-term birth or high birthweight infant during their pregnancy. Individuals reporting a birthweight ≥10 lbs. were more likely to have a high birthweight infant (OR 3.49, 95 % CI 2.73-4.39) and less likely to have a low birthweight infant (OR 0.64, 95 % CI 0.47-0.82). Individuals born preterm were at increased risk for infertility, miscarriage, preeclampsia, gestational diabetes, and delivering a preterm or low birthweight infant., Conclusions: As more individuals born preterm and/or low birthweight survive to adulthood, the incidence and prevalence of poor reproductive outcomes may increase. Women born at extremes of birthweight and prematurity may need to be monitored more closely during their own pregnancies., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study is to examine fetal growth outcomes from agricultural worker households., Methods: Using Arizona 2006 to 2013 birth certificates with parental occupation, we identified N = 623,185 live births by agricultural household status. Logistic regression models estimated adjusted odds ratios (aORs) for macrosomia (>4000 g), postterm birth (>41 weeks), low birth weight (<2500 g), preterm birth (<37 weeks), large for GA, small for GA, and 5-minute APGAR (<7)., Results: Newborns of agricultural households (n = 6371) had a higher risk of macrosomia (aOR, 1.15; 95% CI, 1.05-1.26), large for GA (aOR, 1.12; 95% CI, 1.03-1.22), postterm birth (aOR, 1.20; 95% CI, 1.09-1.33), and low 5-minute APGAR (aOR, 1.39; 95% CI, 1.07-1.81), whereas low birth weight (aOR, 0.85; 95% CI, 0.76-0.96) and preterm birth (aOR, 0.82; 95% CI, 0.74-0.92) were inversely related., Conclusions: Having an agriculture working parent increased the likelihood of fetal overgrowth and low APGAR., Competing Interests: Parra, Harris, Farland, Beamer, and Furlong have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

Basal cell carcinoma (BCC) is the most common cancer in the United States. Sunburn is a modifiable risk factor for BCC. The objective of this project was to synthesize research on BCC and sunburn to quantify the impact and severity of sunburn at different life stages on BCC risk in the general population. A systematic literature search of four electronic databases was conducted and data were extracted by two independent reviewers using standardized forms. Data from 38 studies were pooled using both dichotomous and dose-response meta-analytic methods. BCC risk increased with ever experiencing a sunburn in childhood (OR=1.43, 95% CI: 1.19, 1.72) and with ever experiencing a sunburn in life (OR= 1.40, 95% CI: 1.02, 1.45). Every five sunburns experienced per decade in childhood increased BCC risk by 1.86 (95% CI: 1.73, 2.00) times. Every five sunburns experienced per decade in adulthood increased BCC risk by 2.12 (95% CI: 1.75, 2.57) times and every five sunburns per decade of life increased BCC risk by 1.91 (95% CI: 1.42, 2.58) times. The data on sunburn exposure and BCC show that an increase in number of sunburns at any age increased the risk of BCC. This may inform future prevention efforts., 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: Hysterectomy, oophorectomy, and tubal ligation are common surgical procedures. The literature regarding cardiovascular disease (CVD) risk after these surgeries has focused on oophorectomy with limited research on hysterectomy or tubal ligation. Materials and Methods: Participants in the Nurses' Health Study II ( n  = 116,429) were followed from 1989 to 2017. Self-reported gynecologic surgery was categorized as follows: no surgery, hysterectomy alone, hysterectomy with unilateral oophorectomy, and hysterectomy with bilateral oophorectomy. We separately investigated tubal ligation alone. The primary outcome was CVD based on medical-record confirmed fatal and nonfatal myocardial infarction, fatal coronary heart disease, or fatal and nonfatal stroke. Our secondary outcome expanded CVD to include coronary revascularization (coronary artery bypass graft surgery, angioplasty, stent placement). Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) and were adjusted a priori for confounding factors. We investigated differences by age at surgery (≤50, >50) and menopausal hormone therapy usage. Results: At baseline, participants were on average, 34 years old. During 2,899,787 person-years, we observed 1,864 cases of CVD. Hysterectomy in combination with any oophorectomy was associated with a greater risk of CVD in multivariable-adjusted models (HR hysterectomy with unilateral oophorectomy:1.40 [95% CI: 1.08-1.82]; HR hysterectomy with bilateral oophorectomy:1.27 [1.07-1.51]). Hysterectomy alone, hysterectomy with oophorectomy, and tubal ligation were also associated with an increased risk of combined CVD and coronary revascularization (HR hysterectomy alone: 1.19 [95% CI: 1.02-1.39]; HR hysterectomy with unilateral oophorectomy: 1.29 [1.01-1.64]; HR hysterectomy with bilateral oophorectomy: 1.22 [1.04-1.43]; HR tubal ligation: 1.16 [1.06-1.28]). The association between hysterectomy/oophorectomy and CVD and coronary revascularization risk varied by age at gynecologic surgery, with the strongest association among women who had surgery before age 50 years. Conclusion: Our findings suggest that hysterectomy, alone or in combination with oophorectomy, as well as tubal ligation, may be associated with an increased risk of CVD and coronary revascularization. These findings extend previous research finding that oophorectomy is associated with CVD.

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.)

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.)

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.)

Background and Objective: Migraine is a highly prevalent neurovascular disorder among reproductive-aged women. Whether migraine history and migraine phenotype might serve as clinically useful markers of obstetric risk is not clear. The primary objective of this study was to examine associations of prepregnancy migraine and migraine phenotype with risks of adverse pregnancy outcomes., Methods: We estimated associations of self-reported physician-diagnosed migraine and migraine phenotype with adverse pregnancy outcomes in the prospective Nurses' Health Study II (1989-2009). Log-binomial and log-Poisson models with generalized estimating equations were used to estimate relative risks (RRs) and 95% CIs for gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension, preterm delivery, and low birthweight., Results: The analysis included 30,555 incident pregnancies after cohort enrollment among 19,694 participants without a history of cardiovascular disease, diabetes, or cancer. After adjusting for age, adiposity, and other health and behavioral factors, prepregnancy migraine (11%) was associated with higher risks of preterm delivery (RR = 1.17; 95% CI = 1.05-1.30), gestational hypertension (RR = 1.28; 95% CI = 1.11-1.48), and preeclampsia (RR = 1.40; 95% CI = 1.19-1.65) compared with no migraine. Migraine was not associated with low birthweight (RR = 0.99; 95% CI = 0.85-1.16) or GDM (RR = 1.05; 95% CI = 0.91-1.22). Risk of preeclampsia was somewhat higher among participants with migraine with aura (RR vs no migraine = 1.51; 95% CI = 1.22-1.88) than migraine without aura (RR vs no migraine = 1.30; 95% CI = 1.04-1.61; p- heterogeneity = 0.32), whereas other outcomes were similar by migraine phenotype. Participants with migraine who reported regular prepregnancy aspirin use had lower risks of preterm delivery (<2×/week RR = 1.24; 95% CI = 1.11-1.38; ≥2×/week RR = 0.55; 95% CI = 0.35-0.86; p -interaction < 0.01) and preeclampsia (<2×/week RR = 1.48; 95% CI = 1.25-1.75; ≥2×/week RR = 1.10; 95% CI = 0.62-1.96; p -interaction = 0.39); however, power for these stratified analyses was limited., Discussion: Migraine history, and to a lesser extent migraine phenotype, appear to be important considerations in obstetric risk assessment and management. Future research should determine whether aspirin prophylaxis may be beneficial for preventing adverse pregnancy outcomes among pregnant individuals with a history of migraine., (© 2023 American Academy of Neurology.)

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.

Objective: To describe the characteristics of people who experience changes to their menstrual cycle after COVID-19 vaccination., Design: Longitudinal study., Patient(s): We recruited a volunteer sample with and without a history of SARS-CoV-2 infection who enrolled in the Arizona COVID-19 Cohort (CoVHORT) study and participated in a reproductive sub-cohort who were pre-menopausal, not pregnant, and had received a COVID-19 vaccine in 2021 (n = 545)., Exposure(s): Demographic and reproductive characteristics were collected via self-reports., Main Outcome Measure(s): Information on self-reported changes in the menstrual cycle after COVID-19 vaccination was collected from May 2021 to December 2021. We looked at demographic and reproductive characteristics as predictors of menstrual cycle change., Result(s): The majority of our vaccinated sample received the Pfizer-BioNTech vaccine (58%), and were 26-35 years old (51%), non-Hispanic (84%), and White (88%). Approximately 25% of vaccinated participants reported a change in their menstrual cycle after vaccination; the majority reported changes after their second dose (56%) as compared with their first (18%) and third (14%) doses. The most commonly reported changes were irregular menstruation (43%), increased premenstrual symptoms (34%), increased menstrual pain or cramps (30%), and abnormally heavy or prolonged bleeding (31%). High self-reported perceived stress levels compared with low perceived stress (OR, 2.22; 95% CI 1.12-4.37) and greater body mass index (OR, 1.04; 95% CI 1.00-1.07) were associated with greater odds of experiencing the menstrual cycle changes after the vaccination. Participants having a history of SARS-CoV-2 infection were less likely to report changes in their menstrual cycle after vaccination compared with the participants with no history of SARS-CoV-2 infection (OR, 0.58; 95% CI 0.32-1.04)., Conclusion(s): Among vaccinated participants, approximately 25% of them reported predominantly temporary changes in the menstrual cycle, however, we are unable to determine whether these changes are due to normal cycle variability. The COVID-19 vaccines are safe and effective for everyone, including pregnant people and people trying to conceive; hence, these findings should not discourage vaccination., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Previous research has suggested that women firefighters may have a greater risk of adverse reproductive outcomes compared with non-firefighting women. In this study, we investigated the association between firefighter occupational factors and risk of preterm birth., Methods: This cross-sectional analysis of US firefighters surveyed in 2017 compared preterm birth among firefighters to non-firefighters using age-at-pregnancy-standardised prevalence ratios. Generalised estimating equations estimated relative risks and 95% CIs between firefighter occupational factors (career or volunteer, wildland status, shift schedule, fire responses, work restriction) and preterm birth risk. We adjusted for age-at-pregnancy, education, gravidity, BMI, and smoking and considered effect modification by age-at-pregnancy and career versus volunteer status., Results: Among 934 women who reported 1356 live births, 12% were preterm (n=161). Preterm birth prevalence among firefighters was 1.41 times greater than non-firefighters (95% CI 1.18 to 1.68). Among wildland and combination wildland/structural firefighters, volunteers had 2.82 times the risk of preterm birth (95% CI 1.19 to 6.67) compared with career firefighters. Firefighters who started restricting their work in the 2nd trimester had a nonsignificant 0.67 times lower risk of preterm birth than those who started in the 3rd trimester or did not restrict work at all (95% CI 0.43 to 1.03)., Conclusions: Firefighters may have greater risk of preterm birth than non-firefighters, which could be influenced by roles in the fire service and work restrictions taken., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Post-acute sequelae of COVID-19 (PASC) are conditions that occur or remain at least 28 days after SARS-CoV-2 infection. While some risk factors for PASC have been identified, little is known about pre-existing conditions that render one susceptible to developing PASC. Data from participants (n = 1224) in a longitudinal COVID-19 cohort study in Arizona were used to investigate comorbid conditions associated with PASC. After adjustment of the models for age, BMI, gender, race, and smoking, the following pre-existing conditions were statistically significantly associated with the development of PASC: asthma (OR = 1.54; 95% CI = 1.10-2.15); chronic constipation (OR = 4.29; 95% CI = 1.15-16.00); reflux (OR = 1.54; 95% CI = 1.01-2.34); rheumatoid arthritis (OR = 3.69; 95%CI = 1.15-11.82); seasonal allergies (OR = 1.56; 95% CI = 1.22-1.98); and depression/anxiety (OR = 1.72; 95% CI = 1.17-2.52). When grouping conditions together, statistically significant associations with PASC were observed for respiratory (OR = 1.47; 95% CI = 1.06-2.14); gastrointestinal (OR = 1.62; 95% CI = 1.16-2.26), and autoimmune conditions (OR = 4.38; 95% CI = 1.59-12.06). After adjustment for severity of acute SARS-CoV-2 infection and depression/anxiety, seasonal allergies (OR = 1.48; 95% CI 1.15-1.91) and autoimmune disease (OR = 3.78; 95% CI - 1.31-10.91) remained significantly associated with risk for PASC. These findings indicate that numerous pre-existing conditions may be associated with an increased risk for the development of PASC. Patients with these conditions should consider taking extra steps to avoid infection., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.)

Adenomyosis is a burdensome gynecologic condition that is associated with pelvic pain, dysmenorrhea, and abnormal uterine bleeding, leading to a negative impact on quality of life; and yet is often left undiagnosed. We recruited 108 women undergoing hysterectomy for benign gynecologic conditions and collected non-invasive cervicovaginal lavage samples for immunometabolic profiling. Patients were grouped according to adenomyosis status. We investigated the levels of 72 soluble immune proteins and >900 metabolites using multiplex immunoassays and an untargeted global metabolomics platform. There were statistically significant alterations in the levels of several immune proteins and a large quantity of metabolites, particularly cytokines related to type II immunity and amino acids, respectively. Enrichment analysis revealed that pyrimidine metabolism, carnitine synthesis, and histidine/histamine metabolism were significantly upregulated pathways in adenomyosis. This study demonstrates utility of non-invasive sampling combined with immunometabolic profiling for adenomyosis detection and a greater pathophysiological understanding of this enigmatic condition., Competing Interests: M.M.H.-K is a paid consultant for Freya Biosciences. None of this work related to, was shared with, or was licensed to this company or any other commercial entity. G.M.L., P.Ł., H.C., D.J.R., J.M., N.D.M., and L.V.F. declare no competing interests., (© 2022 The Authors.)

Background: Women with endometriosis may have an increased risk of adverse pregnancy outcomes. Research has focused on infertility clinic populations limiting generalisability. Few studies report differences by endometriosis severity., Objectives: We investigated the relationships between endometriosis diagnosis, staging and typology and pregnancy outcomes among an operative and population-based sample of women., Methods: Menstruating women ages 18-44 years enrolled in the ENDO Study (2007-2009), including the operative cohort: 316 gravid women undergoing laparoscopy/laparotomy at surgical centres in Utah and California; and the population cohort: 76 gravid women from the surgical centres' geographic catchment areas. Pregnancy outcomes were ascertained by questionnaire and included all pregnancies prior to study enrolment. Endometriosis was diagnosed via surgical visualisation in the operative cohort and pelvic magnetic resonance imaging in the population cohort. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were estimated using generalised linear mixed models for pregnancy outcomes, adjusting for women's age at study enrolment and at pregnancy, surgical site, body mass index and lifestyle factors., Results: Women in the operative cohort with visualised endometriosis (n = 109, 34%) had a lower prevalence of live births, aPR 0.94 (95% CI 0.85, 1.03) and a higher prevalence of miscarriages, aPR 1.48 (95% CI 1.23, 1.77) compared with women without endometriosis. The direction and magnitude of estimates were similar in the population cohort. Women with deep endometriosis were 2.98-fold more likely (95% CI 1.12, 7.95) to report a miscarriage compared with women without endometriosis after adjusting for women's age at study enrolment and at pregnancy, surgical site and body mass index. No differences were seen between endometriosis staging and pregnancy outcomes., Conclusions: While there was no difference in number of pregnancies among women with and without endometriosis in a population-based sample, pregnancy loss was more common among women with endometriosis, notably among those with deep endometriosis., (© 2022 John Wiley & Sons Ltd.)

Background: Despite anecdotal reports, the impacts of SARS-CoV-2 infection or COVID-19 vaccination on menstrual health have not been systemically investigated., Objective: This study aimed to examine the associations of SARS-CoV-2 infection and COVID-19 vaccination with menstrual cycle characteristics., Study Design: This study prospectively observed 3858 premenopausal women in the Nurses' Health Study 3 living in the United States or Canada who received biannual follow-up questionnaires between January 2011 and December 2021 and completed additional monthly and quarterly surveys related to the COVID-19 pandemic between April 2020 and November 2021. History of positive SARS-CoV-2 test, COVID-19 vaccination status, and vaccine type were self-reported in surveys conducted in 2020 and 2021. Current menstrual cycle length and regularity "before COVID-19" were reported at baseline between 2011 and 2016, and current menstrual cycle length and regularity "after COVID-19" were reported in late 2021. Pre- to post-COVID change in menstrual cycle length and regularity was calculated between reports. Logistic or multinomial logistic regression models were used to assess the associations between SARS-CoV-2 infection and COVID-19 vaccination and change in menstrual cycle characteristics., Results: The median age at baseline and the median age at end of follow-up were 33 years (range, 21-51) and 42 years (range, 27-56), respectively, with a median follow-up time of 9.2 years. This study documented 421 SARS-CoV-2 infections (10.9%) and 3527 vaccinations (91.4%) during follow-up. Vaccinated women had a higher risk of increased cycle length than unvaccinated women (odds ratio, 1.48; 95% confidence interval, 1.00-2.19), after adjusting for sociodemographic and behavioral factors. These associations were similar after in addition accounting for pandemic-related stress. COVID-19 vaccination was only associated with change to longer cycles in the first 6 months after vaccination (0-6 months: odds ratio, 1.67 [95% confidence interval, 1.05-2.64]; 7-9 months: odds ratio, 1.43 [95% confidence interval, 0.96-2.14]; >9 months: odds ratio, 1.41 [95% confidence interval, 0.91-2.18]) and among women whose cycles were short, long, or irregular before vaccination (odds ratio, 2.82 [95% confidence interval, 1.51-5.27]; odds ratio, 1.10 [95% confidence interval, 0.68-1.77] for women with normal length, regular cycles before vaccination). Messenger RNA and adenovirus-vectored vaccines were both associated with this change. SARS-CoV-2 infection was not associated with changes in usual menstrual cycle characteristics., Conclusion: COVID-19 vaccination may be associated with short-term changes in usual menstrual cycle length, particularly among women whose cycles were short, long, or irregular before vaccination. The results underscored the importance of monitoring menstrual health in vaccine clinical trials. Future work should examine the potential biological mechanisms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Study Question: Do women with polycystic ovary syndrome (PCOS) have a greater risk of adverse pregnancy complications (gestational diabetes, preeclampsia, cesarean section, placental abnormalities) and neonatal outcomes (preterm birth, small for gestational age, prolonged delivery hospitalization) compared to women without a PCOS diagnosis and does this risk vary by BMI, subfertility and fertility treatment utilization?, Summary Answer: Deliveries to women with a history of PCOS were at greater risk of complications associated with cardiometabolic function, including gestational diabetes and preeclampsia, as well as preterm birth and prolonged length of delivery hospitalization., What Is Known Already: Prior research has suggested that women with PCOS may be at increased risk of adverse pregnancy outcomes. However, findings have been inconsistent possibly due to lack of consistent adjustment for confounding factors, small samples size and other sources of bias., Study Design, Size, Duration: Massachusetts deliveries among women ≥18 years old during 2013-2017 from state vital records linked to hospital discharges, observational stays and emergency department visits were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and the Massachusetts All-Payers Claims Database (APCD)., Participants/materials, Setting, Methods: PCOS was identified by ICD9 and ICD10 codes in APCD prior to index delivery. Relative risks (RRs) and 95% CI for pregnancy and delivery complications were modeled using generalized estimating equations with a log link and a Poisson distribution to take multiple cycles into account and were adjusted a priori for maternal age, BMI, race/ethnicity, education, plurality, birth year, chronic hypertension and chronic diabetes. Tests for homogeneity investigated differences between maternal pre-pregnancy BMI categories (<30, ≥30, <25 and ≥25 kg/m2) and between non-infertile deliveries and deliveries that used ART or had a history of subfertility (defined by birth certificates, SART CORS records, APCD or hospital records)., Main Results and the Role of Chance: Among 91 825 deliveries, 3.9% had a history of PCOS. Women with a history of PCOS had a 51% greater risk of gestational diabetes (CI: 1.38-1.65) and a 25% greater risk of preeclampsia (CI: 1.15-1.35) compared to women without a diagnosis of PCOS. Neonates born to women with a history of PCOS were more likely to be born preterm (RR: 1.17, CI: 1.06-1.29) and more likely to have a prolonged delivery hospitalization after additionally adjusting for gestational age (RR: 1.23, CI: 1.09-1.40) compared to those of women without a diagnosis of PCOS. The risk for gestational diabetes for women with PCOS was greater among women with a pre-pregnancy BMI <30 kg/m2., Limitations, Reasons for Caution: PCOS was defined by ICD documentation prior to delivery so there may be women with undiagnosed PCOS or PCOS diagnosed after delivery included in the unexposed group. The study population is limited to deliveries within Massachusetts among most private insurance payers and inpatient or observational hospitalization in Massachusetts during the follow-up window, therefore there may be diagnoses and or deliveries outside of the state or outside of our sample that were not captured., Wider Implications of the Findings: In this population-based study, women with a history of PCOS were at greater risk of pregnancy complications associated with cardiometabolic function and preterm birth. Obstetricians should be aware of patients' PCOS status and closely monitor for potential pregnancy complications to improve maternal and infant perinatal health outcomes., Study Funding/competing Interest(s): This work was supported by the NIH (R01HD067270). S.A.M. receives grant funding from NIH, AbbVie and the Marriot Family Foundation; payment/honoraria from the University of British Columbia, World Endometriosis Research Foundation and Huilun Shanghai; travel support for attending meetings for ESHRE 2019, IASP 2019, National Endometriosis Network UK meeting 2019; SRI 2022, ESHRE 2022; participates on the data safety monitoring board/advisory board for AbbVie, Roche, Frontiers in Reproductive Health; and has a leadership role in the Society for Women's Health Research, World Endometriosis Research Foundation, World Endometriosis Society, American Society for Reproductive Medicine and ESHRE. The other authors have no conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2022. 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: Menstrual cycle characteristics may be associated with an increased risk of cardiovascular disease (CVD). However, existing studies are limited, and few have explored the mediating role of established CVD risk factors., Objective: To explore the associations of menstrual cycle characteristics across the reproductive lifespan with the risk of CVD and to what extent these associations were mediated by hypercholesterolemia, chronic hypertension, and type 2 diabetes., Design, Setting, and Participants: This cohort study prospectively followed Nurses' Health Study II participants between 1993 and 2017 who reported menstrual cycle regularity and length for ages 14 to 17 years and 18 to 22 years at enrollment in 1989 and updated current cycle characteristics in 1993 (at ages 29 to 46 years). Data analysis was performed from October 1, 2019, to January 1, 2022., Exposures: Menstrual cycle regularity and length across the reproductive lifespan., Main Outcomes and Measures: Incident CVD events of interest, including fatal and nonfatal coronary heart disease (CHD; myocardial infarction [MI] or coronary revascularization) and stroke., Results: A total of 80 630 Nurses' Health Study II participants were included in the analysis, with a mean (SD) age of 37.7 (4.6) years and body mass index of 25.1 (5.6) at baseline. Over 24 years of prospective follow-up, 1816 women developed their first CVD event. Multivariable Cox proportional hazards models showed that, compared with women reporting very regular cycles at the same ages, women who had irregular cycles or no periods at ages 14 to 17, 18 to 22, or 29 to 46 years had hazard ratios for CVD of 1.15 (95% CI, 0.99-1.34), 1.36 (95% CI, 1.06-1.75), and 1.40 (95% CI, 1.14-1.71), respectively. Similarly, compared with women reporting a cycle length of 26 to 31 days, women reporting a cycle length 40 days or more or a cycle too irregular to estimate from ages 18 to 22 or 29 to 46 years had hazard ratios for CVD of 1.44 (95% CI, 1.13-1.84) and 1.30 (95% CI, 1.09-1.57), respectively. Mediation analyses showed that subsequent development of hypercholesteremia, chronic hypertension, and type 2 diabetes only explained 5.4% to 13.5% of the observed associations., Conclusions and Relevance: In this cohort study, both irregular and long menstrual cycles were associated with increased rates of CVD, which persisted even after accounting for subsequently established CVD risk factors.

Background: Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up., Methods: Participants in the NHSII cohort study (Nurses' Health Study II) were followed from 1989 when they were between the ages of 25 to 42 until 2017 for development of incident stroke (ischemic and hemorrhagic). Cox proportional hazard models were used to calculate hazard ratios and 95% CI, with adjustment for potential confounding variables (alcohol intake, body mass index at age 18, current body mass index, age at menarche, menstrual cycle pattern in adolescence, current menstrual cycle pattern, parity, oral contraceptive use history, smoking history, diet quality, physical activity, NSAID use, aspirin use, race/ethnicity, and income). We estimated the proportion of the total association mediated by history of hypertension, hypercholesterolemia, hysterectomy/oophorectomy, and hormone therapy. We also tested for effect modification by age (<50, ≥ 50 years), infertility history, body mass index (<25, ≥ 25 kg/m 2 ), and menopausal status., Results: We documented 893 incident cases of stroke during 2 770 152 person-years of follow-up. Women with laparoscopically confirmed endometriosis had a 34% greater risk of stroke in multivariable-adjusted models (hazard ratio, 1.34 [95% CI, 1.10-1.62]), compared to those without a history of endometriosis. Of the total association of endometriosis with risk of stroke, the largest proportion was attributed to hysterectomy/oophorectomy (39% mediated [95% CI, 14%-71%]) and hormone therapy (16% mediated [95% CI, 5%-40%]). We observed no differences in the relationship between endometriosis and stroke by age, infertility history, body mass index, or menopausal status., Conclusions: We observed that women with endometriosis were at elevated risk of stroke. Women and their health care providers should be aware of endometriosis history, maximize primary cardiovascular prevention, and discuss signs and symptoms of cardiovascular disease.

Numerous studies have demonstrated that assisted reproductive technology (ART: defined here as including only in vitro fertilization and related technologies) is associated with increased adverse pregnancy, neonatal, and childhood developmental outcomes, even in singletons. The comparison group for many had often been a fertile population that conceived without assistance. The Massachusetts Outcome Study of Assisted Reproductive Technology (MOSART) was initiated to define a subfertile population with which to compare ART outcomes. Over more than 10 years, we have used the MOSART database to study pregnancy abnormalities and delivery complications but also to evaluate ongoing health of women, infants, and children. This article will review studies from MOSART in the context of how they compare with those of other investigations. We will present MOSART studies that identified the influence of ART and subfertility/infertility on adverse pregnancy (pregnancy hypertensive disorder, gestational diabetes, placental abnormality) and delivery (preterm birth, low birthweight) outcomes as well as on maternal and child hospitalizations. We will provide evidence that although subfertility/infertility increases the risk of adverse outcomes, there is additional risk associated with the use of ART. Studies exploring the contribution of placental abnormalities as one factor adding to this increased ART-associated risk will be described., Competing Interests: Conflicts of interest: All authors’ institutions received support and travel funds from one or both grants. There are no other conflicts of interest.

Background: The etiology of endometriosis is not well understood. Limited evidence suggests that dietary factors influence risk, but prospective data related to carbohydrate, fiber, and gluten consumption are scarce. Despite this, recommendations concerning fiber, gluten intake, and endometriosis are pervasive in the lay literature., Objectives: We aimed to investigate the associations of carbohydrate quality [glycemic index (GI) and glycemic load (GL)], fiber intake (total, legume, vegetable, cruciferous vegetable, fruit, cereal), and gluten intake with incident laparoscopically confirmed endometriosis., Methods: This was a prospective cohort study using data collected from 81,961 premenopausal women in the Nurses' Health Study II (mean age = 36 y in 1991). Diet was assessed with a validated FFQ every 4 y. Cox proportional hazards models were used to calculate rate ratios (RRs) and 95% CIs., Results: A total of 3810 incident cases of laparoscopically confirmed endometriosis were reported over 24 y of follow-up. Women in the highest quintile of GI had 12% (95% CI: 1.01, 1.23; Ptrend = 0.03) higher risk of endometriosis diagnosis than those in the lowest quintile. Total vegetable and cruciferous vegetable fiber intakes were also associated with higher risk (highest compared with lowest quintile RR: 1.13; 95% CI: 1.02, 1.24; Ptrend = 0.004 and RR: 1.17; 95% CI: 1.06, 1.29; Ptrend = 0.02, respectively). Higher intake of fruit fiber was associated with lower risk of endometriosis but the association was not significant after adjusting for the Alternative Healthy Eating Index. Gluten intake was also associated with lower risk (highest compared with lowest quintile RR: 0.91; 95% CI: 0.80, 1.02; Ptrend = 0.01), but these results were not consistent in direction nor statistical significance across sensitivity analyses. No association was observed for GL or total, legume, or cereal fiber intake., Conclusions: Our findings suggest that carbohydrate quality and specific types of fiber-total vegetable and cruciferous vegetable fiber-are associated with endometriosis diagnosis in premenopausal women. These results also indicate it is unlikely that gluten intake is a strong factor in the etiology or symptomatology of endometriosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: Studies have reported that antidiabetic medications (ADMs) were associated with lower risk of dementia, but current findings are inconsistent. This study compared the risk of dementia onset in patients with type 2 diabetes (T2D) treated with sulfonylurea (SU) or thiazolidinedione (TZD) to patients with T2D treated with metformin (MET)., Research Design and Methods: This is a prospective observational study within a T2D population using electronic medical records from all sites of the Veterans Affairs Healthcare System. Patients with T2D who initiated ADM from January 1, 2001, to December 31, 2017, were aged ≥60 years at the initiation, and were dementia-free were identified. A SU monotherapy group, a TZD monotherapy group, and a control group (MET monotherapy) were assembled based on prescription records. Participants were required to take the assigned treatment for at least 1 year. The primary outcome was all-cause dementia, and the two secondary outcomes were Alzheimer's disease and vascular dementia, defined by International Classification of Diseases (ICD), 9th Revision, or ICD, 10th Revision, codes. The risks of developing outcomes were compared using propensity score weighted Cox proportional hazard models., Results: Among 559 106 eligible veterans (mean age 65.7 (SD 8.7) years), the all-cause dementia rate was 8.2 cases per 1000 person-years (95% CI 6.0 to 13.7). After at least 1 year of treatment, TZD monotherapy was associated with a 22% lower risk of all-cause dementia onset (HR 0.78, 95% CI 0.75 to 0.81), compared with MET monotherapy, and 11% lower for MET and TZD dual therapy (HR 0.89, 95% CI 0.86 to 0.93), whereas the risk was 12% higher for SU monotherapy (HR 1.12 95% CI 1.09 to 1.15)., Conclusions: Among patients with T2D, TZD use was associated with a lower risk of dementia, and SU use was associated with a higher risk compared with MET use. Supplementing SU with either MET or TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)