Female sexual function and distress and time-to-pregnancy in a prospective preconception cohort.

BACKGROUND: Fertility success among mixed-sex couples often depends on frequency and timing of sexual intercourse, yet little research has evaluated the association between preconception sexual function and time-to-pregnancy (TTP). OBJECTIVE: (s): To evaluate the effects of female sexual dysfunction, distress related to sexual functioning, and painful intercourse on TTP. STUDY DESIGN: We followed 2,500 participants from Pregnancy Study Online (PRESTO), a prospective cohort study of self-identified females attempting pregnancy without the use of fertility treatments. Participants enrolled between 2021 and 2024. Thirty days after enrollment, participants completed a supplemental questionnaire that contained questions about sexual health, including a modified version of the 6-item Female Sexual Function Index (score range 2-30, score ≤19 defined as sexual dysfunction) and the Female Sexual Distress Scale (score range 0-48, score ≥20 defined as clinically-relevant distress), which assess experiences in the previous 4 weeks. Participants completed the supplemental questionnaire no later than 6 months after initiating conception attempts. We estimated TTP based on self-reported pregnancy status on follow-up questionnaires completed every 8 weeks for up to 12 months. We used proportional probabilities regression to calculate fecundability ratios (FRs) and 95% confidence intervals (CIs) relating exposure measures with TTP, adjusting for a range of pre-specified confounders. As an exploratory analysis, we evaluated individual domains of sexual function (i.e., interest, arousal, orgasm, lubrication, and satisfaction) in relation to TTP. RESULTS: The study population was primarily non-Hispanic White, high income, with college or graduate education. Exposure prevalence was 20.1% for female sexual dysfunction, 8.8% for distress, and 29.6% for any pain with intercourse. We observed no association between FSD and TTP (adjusted FR 1.00, 95% CI 0.890, 1.13) when FSD was defined using a clinically-validated cut point, but observed that those in the first, second, and third quartile of scores had delayed conception compared to those in the fourth (highest function) (adjusted FRs 0.90, 95% CI 0.76, 1.06; 0.88, 95% CI 0.75, 1.04; and 0.90, 95% CI 0.77, 1.04, respectively). We found 18% reduced fecundability among those with sexual distress as defined by a clinically-validated cut point compared to those without (adjusted FR 0.82, 95% CI 0.69, 0.98). Participants reporting painful intercourse most or all the time had a longer TTP than those reporting no pain (adjusted FR 0.81, 95% CI 0.62, 1.06). In exploratory analyses, lower function in orgasm and lubrication domains, but not interest, desire, and arousal, were associated with longer TTP. CONCLUSION(S): Preconception sexual dysfunction, specifically distress and frequent painful intercourse, was associated with delayed conception. Preconception clinical assessment of sexual function, including discussion of individual domains of sexual function, may elucidate important modifiable issues.

Cadmium exposure and risk of hypertension: a systematic review and dose-response meta-analysis.

BACKGROUND: Exposure to environmental toxic metals represents a significant global public health concern. Many studies have reported that cadmium (Cd) exposure increases the risk of hypertension. Since the shape of such relation has not been well characterized, we assessed it by performing a systematic review and dose-response meta-analysis of human studies. METHODS: We searched the literature through September 5, 2024 to identify papers related to Cd, hypertension, and blood pressure. Inclusion criteria were: observational design, adult population, assessment of exposure using Cd biomarkers, and availability of exposure category-specific risk estimates for hypertension. We performed a dose-response meta-analysis of the results from included studies. RESULTS: Of the 18 studies published between 2006-2024, most had a cross-sectional design. Cd was measured in whole blood and/or urine in almost all studies, whereas only two studies measured Cd in serum. The dose-response meta-analysis indicated an almost linear relation between urinary Cd concentrations and hypertension risk with RR=1.18, 95% CI 1.02-1.37 at 2.0 µg/g creatinine compared with no exposure. In contrast, the association between blood Cd concentrations and hypertension risk was non-linear: there was a steep monotonic increase in risk for Cd concentrations below 2 µg/L, reaching a RR of 1.48 (95% CI 1.17-1.86) at 2.0 µg/L, after which a plateau seemed reached. We found similar trends when restricting to studies of Asian population, while when considering North American studies, hypertension risk increased above 1.0 µg/g creatinine. CONCLUSIONS: In this dose-response meta-analysis, risk of hypertension showed a non-linear positive association with blood Cd concentrations and a linear positive association with urinary Cd concentrations. Inconsistency in the shape of associations could relate to the different timing of exposure assessed by the biomarkers or the alteration Cd excretion at increasing exposure levels. Mitigation of Cd exposure is confirmed as a public health priority for chronic disease prevention.

Diabetes and uterine fibroid diagnosis in midlife: Study of Women's Health Across the Nation (SWAN).

BACKGROUND: Fibroids are non-cancerous uterine tumors potentially associated with cardiovascular risk factors. We examined prospectively associations of glucose, insulin, sex hormone binding globulin (SHBG), and diabetes with incidence of fibroid diagnoses in midlife. METHODS: Participants in the Study of Women's Health Across the Nation (SWAN) cohort (n=2570) reported fibroid diagnoses at enrollment (1996-1997) and 13 follow-up visits (1996-2013). At all visits, we measured glucose, insulin, and SHBG in fasting blood samples and calculated homeostatic model assessment for insulin resistance (HOMA-IR). Diabetes was defined using glucose levels, self-reported diabetes, or diabetes medication use. We used discrete-time survival models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of time-varying biomarkers and diabetes with incident fibroid diagnoses, adjusted for demographics and healthcare utilization. We also evaluated effect modification by menopausal status. RESULTS: At baseline, 2.7% of participants (n=70) were using diabetes medication. Time-varying glucose, insulin, HOMA-IR, and SHBG were not associated with fibroid diagnosis. However, diabetes was associated with a 28% lower incidence of fibroid diagnosis (adjusted HR: 0.72, 95% CI: 0.44, 1.17), driven by participants using metformin (adjusted HR: 0.49, 95% CI: 0.21, 1.12), though precision was limited. After stratification by menopausal status, higher HOMA-IR and insulin were associated with greater incidence of fibroid diagnosis during premenopause but not perimenopause, while the inverse association between diabetes and fibroids was strongest during perimenopause. CONCLUSION: The effect of diabetes and biomarkers on fibroids may vary by menopausal status. Fibroid risk may increase with insulin resistance and decrease with diabetes treatment.

Persistent endocrine-disrupting chemicals and incident uterine leiomyomata: A mixtures analysis.

BACKGROUND: Uterine leiomyomata (UL; fibroids) are hormone-dependent neoplasms that can cause significant gynecologic morbidity. Studies have documented associations between concentrations of persistent endocrine-disrupting chemicals (EDCs) and UL incidence; however, few have assessed the effects of EDC mixtures on UL. METHODS: In the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study, participants attended study visits at baseline and approximately every 20 months for up to 10 years; at each visit, they completed questionnaires, provided blood samples, and underwent standardized ultrasound examinations. In baseline plasma samples (n = 1155), we quantified concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides using high-resolution mass spectrometry. We selected nine EDCs detected in >60 % of samples (4 PCBs, 4 PBDEs, and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE)) and conducted probit Bayesian kernel machine regression with hierarchical variable selection to estimate effects of the EDC mixture and individual EDCs on UL incidence, adjusting for potential confounders. RESULTS: During 10 years of follow-up, 32 % of participants developed ultrasound-detected UL. The EDC mixture was not appreciably associated with the probit of UL (ß comparing all EDCs at their 75th vs. 50th percentile:= - 0.01, 95 % credible interval [CrI]: -0.11, 0.10). However, individual EDC concentrations were associated with UL in opposing directions: PCB138/158 was positively associated with UL (ß for 25th-to-75th-percentile increase when all other chemicals were set to their 50th percentile = 0.18, 95 % CrI: -0.09, 0.44), whereas PBDE99 and p,p'-DDE were inversely associated with UL (ß = -0.06, 95 % CrI: -0.21, 0.10 and ß = -0.12, 95 % CrI: -0.34, 0.10, respectively). There was little evidence of interaction between EDCs. CONCLUSION: In this prospective ultrasound study, a mixture of persistent EDCs was not appreciably associated with incident UL during 10 years of follow-up, but individual EDCs were associated with UL in opposite directions.

The association between the use of fertility indicators and fecundability in a Danish preconception cohort.

BACKGROUND: The use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility-promoting tools. OBJECTIVE: To investigate the association between fertility indicators and fecundability in Danish women trying to conceive. METHODS: Web-based preconception cohort study. We analysed data from 11,328 females aged 18-49 years trying to conceive without fertility treatment for ≤6 menstrual cycles, from the Danish SnartGravid.dk and SnartForældre.dk cohorts (2007-2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT]). Time to pregnancy was measured in menstrual cycles ascertained by self-reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CIs) using proportional probabilities regression models adjusted for age, socio-economic position, health indicators, reproductive history and gynaecological factors. RESULTS: Fertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non-use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to ≤2 cycles of attempt time and two cycles of follow-up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31). CONCLUSION: In this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator.

Specifying a target trial protocol to estimate the effect of preconception treatment of periodontitis on time-to-pregnancy: A commentary and applied example.

BACKGROUND: The target trial framework was developed as a strategy to design and analyze observational epidemiologic studies with the aim of reducing bias due to analytic decisions. It involves designing a hypothetical randomized trial to answer a question of interest and systematically considering how to use observational data to emulate each trial component. AIMS: The primary aim of this paper is to provide a detailed example of the application of the target trial framework to a research question in oral epidemiology. MATERIALS AND METHODS: We describe the development of a hypothetical target trial and emulation protocol to evaluate the effect of preconception periodontitis treatment on time-to-pregnancy. We leverage data from Pregnancy Study Online (PRESTO), a preconception cohort, to ground our example in existing observational data. We discuss the decision-making process for each trial component, as well as limitations encountered. RESULTS: Our target trial application revealed data limitations that precluded us from carrying out the proposed emulation. Implications for data quality are discussed and we provide recommendations for researchers interested in conducting trial emulations in the field of oral epidemiology. DISCUSSION: The target trial framework has the potential to improve the validity of observational research in oral health, when properly applied. CONCLUSION: We encourage the broad adoption of the target trial framework to the field of observational oral health research and demonstrate its value as a tool to identify directions for future research.

Effective and inclusive mentorship in the field of epidemiology.

Quality mentoring improves outcomes across career stages, including a sense of belonging, persistence, and productivity. However, the status quo in mentorship culture-including in epidemiology-is an ad hoc approach. This pervasive culture adversely affects individual mentees and the entire scientific research enterprise. Public health disciplines such as epidemiology bear a distinct responsibility to foster an inclusive mentorship culture, ensuring the next generation is equipped not only with methodological expertise but also with a commitment to diversity, equity, inclusion, and the principles of public health. In this commentary, we outline the primary attributes of effective mentors, core competencies, and the evidence base underlying how mentors can improve their skills with comprehensive training. We call on mentors, as well as institutional leaders, to make personal and structural changes, such as requiring mentor training, implementing evidence-based tools (e.g., individual development plans), and regularly evaluating mentorship quality. Institutional leaders can remove barriers (e.g., costs to enroll in mentor training) and facilitate mentorship in non-monetary ways, for example, by making it a formal part of the promotion process. Mentors and leaders must champion these changes, fortifying not only individual career trajectories but also advancing scientific integrity, inclusivity, and justice within the epidemiologic community.

EXPOSURE TO AMBIENT HEAT AND RISK OF SPONTANEOUS ABORTION: A CASE-CROSSOVER STUDY.

BACKGROUND: Few epidemiologic studies have examined the association of ambient heat with spontaneous abortion, a common and devastating pregnancy outcome. METHODS: We conducted a case-crossover study nested within Pregnancy Study Online, a preconception cohort study (2013-2022). We included all participants reporting spontaneous abortion (n=1,524). We defined the case window as the 7 days preceding the event and used time-stratified referent selection to select control windows matched on calendar month and day of week. Within each 7-day case and control window, we measured mean, maximum, and minimum of daily maximum outdoor air temperatures. We fit splines to examine non-linear relationships across the entire year and conditional logistic regression to estimate odds ratios (OR) and 95% CI of spontaneous abortion with increases in temperature during the warm season (May-September) and decreases during the cool season (November-March). RESULTS: We found evidence of a U-shaped association between outdoor air temperature and spontaneous abortion risk based on year-round data. When restricting to warm season events (n=657), the OR for a 10-percentile increase in the mean of lag 0-6 daily maximum temperatures was 1.1 (95% CI: 0.96, 1.2) and, for the maximum, 1.1 (95% CI: 0.99, 1.2). The OR associated with any extreme heat days (>95th county-specific percentile) in the preceding week was 1.2 (95% CI: 0.95, 1.5). Among cool season events (n=615), there was no appreciable association between lower temperatures and spontaneous abortion risk. CONCLUSION: Our study provides evidence of an association between high outdoor temperatures and incidence of spontaneous abortion.

Agreement Between the National Cancer Institute's diet history questionnaire II and III in a preconception cohort.

Food frequency questionnaires require updating over time, due to population changes in diet, posing analytical challenges in consistently measuring diet in prospective studies. We compared reliability and agreement between nutrients in two versions of the National Cancer Institute's web-based Diet History Questionnaire (DHQ, III vs. II) in an ongoing North American preconception study. We invited 51 consecutively-enrolled U.S. female participants aged 21-45 years to complete both DHQ versions within a 2-week period, in a randomized order. We compared 30 nutrients from both DHQ versions and calculated within-person reliability using intraclass correlation coefficients (ICCs). Bland-Altman plots and 95% limits of agreement (LOA) were generated to assess nutrient agreement between DHQ versions. We observed highest reliability in percent energy from carbohydrates and cholesterol (ICCs: 0.88; 95% CI: 0.80-0.93) and lowest for percent energy from protein and vitamin D (ICCs: 0.56; 95% CI: 0.34-0.72). At the group level, all nutrients had most observations within the LOA. Bland-Altman plots showed assessment differences between DHQs for protein, fat, monounsaturated fat, and vitamin D. The remaining nutrients showed good agreement and good-to-moderate reliability. Some nutrients may require adjustment and calibration analysis before using them interchangeably across DHQ versions.

Perinatal Outcomes Associated With Metformin Use During Pregnancy in Women With Pregestational Type 2 Diabetes Mellitus.

OBJECTIVE: We emulated a modified randomized trial (Metformin in Women With Type 2 Diabetes in Pregnancy [MiTy]) to compare the perinatal outcomes in women continuing versus discontinuing metformin during pregnancy among those with type 2 diabetes treated with metformin plus insulin before pregnancy. RESEARCH DESIGN AND METHODS: This study used two health care claims databases (U.S., 2000-2020). Pregnant women age 18-45 years with type 2 diabetes who were treated with metformin plus insulin at conception were eligible. The primary outcome was a composite of preterm birth, birth injury, neonatal respiratory distress, neonatal hypoglycemia, and neonatal intensive care unit admission. Secondary outcomes included the components of the primary composite outcome, gestational hypertension, preeclampsia, maternal hypoglycemia, cesarean delivery, infants large for gestational age, infants small for gestational age (SGA), sepsis, and hyperbilirubinemia. We adjusted for potential baseline confounders, including demographic characteristics, comorbidities, and proxies for diabetes progression. RESULTS: Of 2,983 eligible patients, 72% discontinued use of metformin during pregnancy. The average age at conception was 32 years, and the prevalence of several comorbidities was higher among continuers. The risk of the composite outcome was 46% for continuers and 48% for discontinuers. The adjusted risk ratio was 0.92 (95% CI 0.81, 1.03). Risks were similar between treatments and consistent between databases for most secondary outcomes, except for SGA, which was elevated in continuers only in the commercially insured population. CONCLUSIONS: Our findings were consistent with those reported in the MiTy randomized trial. Continuing metformin during pregnancy was not associated with increased risk of a neonatal composite adverse outcome. However, a possible metformin-associated risk of SGA warrants further consideration.

Residential Proximity to Oil and Gas Development and Mental Health in a North American Preconception Cohort Study: 2013-2023.

Objectives. To evaluate associations between oil and gas development (OGD) and mental health using cross-sectional data from a preconception cohort study, Pregnancy Study Online. Methods. We analyzed baseline data from a prospective cohort of US and Canadian women aged 21 to 45 years who were attempting conception without fertility treatment (2013-2023). We developed residential proximity measures for active OGD during preconception, including distance from nearest site. At baseline, participants completed validated scales for perceived stress (10-item Perceived Stress Scale, PSS) and depressive symptoms (Major Depression Inventory, MDI) and reported psychotropic medication use. We used log-binomial regression and restricted cubic splines to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). Results. Among 5725 participants across 37 states and provinces, residence at 2 km versus 20 to 50 km of active OGD was associated with moderate to high perceived stress (PSS ≥ 20 vs < 20: PR = 1.08; 95% CI = 0.98, 1.18), moderate to severe depressive symptoms (MDI ≥ 20 vs < 20: PR = 1.27; 95% CI = 1.11, 1.45), and psychotropic medication use (PR = 1.11; 95% CI = 0.97, 1.28). Conclusions. Among North American pregnancy planners, closer proximity to OGD was associated with adverse preconception mental health symptomatology. (Am J Public Health. 2024;114(9):923-934. https://doi.org/10.2105/AJPH.2024.307730).

Associations of per- and polyfluoroalkyl substances with uterine leiomyomata incidence and growth: a prospective ultrasound study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products. OBJECTIVE: We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity. METHODS: We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL. RESULTS: In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth. IMPACT STATEMENT: In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development.

Association between COVID-19 vaccination and menstruation: a state of the science review.

INTRODUCTION: Menstrual health is a key patient-reported outcome beyond its importance as a general indicator of health and fertility. However, menstrual function was not measured in the clinical trials of COVID-19 vaccines. The purpose of this review was to synthesise the existing literature on the relationship between COVID-19 vaccination and menstrual health outcomes. METHODS: A PubMed search to 31 October 2023 identified a total of 53 publications: 11 prospective cohort studies, 11 retrospective cohort studies or registry-based cohort studies, and 31 cross-sectional or retrospective case-control studies. RESULTS: Identified studies were generally at moderate-to-high risk of bias due to retrospective design, interviewer bias, and failure to include a non-vaccinated control group. Nonetheless, the bulk of the literature demonstrates that COVID-19 vaccine is associated with temporary changes in menstrual characteristics (cycle length and flow) and menstrual pain. Follicular phase (at the time of vaccination) is associated with greater increases in cycle length. Evidence suggests temporary post-vaccine menstrual changes in adolescents, abnormal vaginal bleeding in postmenopausal individuals, and a potential protective effect of using hormonal contraception. CONCLUSIONS: In this review we found evidence supporting an association between the COVID-19 vaccine and menstrual health outcomes. Given the importance of menstrual function to overall health, we recommend that all future vaccine trials include menstruation as a study outcome. Future vaccine studies should include rigorous assessment of the menstrual cycle as an outcome variable to limit sources of bias, identify biological mechanisms, and elucidate the impact of stress.

Cervical intraepithelial neoplasia and fecundability: a prospective cohort study.

STUDY QUESTION: Is cervical intraepithelial neoplasia (CIN) associated with reduced fecundability, defined as the probability of conceiving per menstrual cycle? SUMMARY ANSWER: Overall, we observed no meaningful association between CIN and fecundability, regardless of surgical status, although a recent diagnosis of moderate or severe CIN might be associated with slightly reduced fecundability for 2 years after diagnosis. WHAT IS KNOWN ALREADY: About 15% of couples experience infertility. Few studies have examined the influence of CIN on fertility, and the results have been inconsistent. No study has investigated the association between fecundability and pathologist-reported CIN diagnoses, particularly with respect to the recency of the specific CIN diagnoses. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 9586 women trying to conceive. The women were enrolled from 1 June 2007 to 3 February 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women were invited to complete a baseline questionnaire and bimonthly follow-up questionnaires for up to 12 months or until pregnancy occurred. Data on cervical cytologies and biopsies were retrieved from The National Pathology Registry (DNPR), which holds records of all cervical specimens examined in Denmark. Women were categorized based on their most severe diagnosis of CIN: no lesion, other cervical changes, mild CIN (CIN1), or moderate/severe CIN (CIN2+) with or without surgery. To investigate the association between CIN and fecundability, we computed fecundability ratios (FR) and 95% confidence intervals (CI) using a proportional probabilities regression model. We adjusted for age at study entry, partner age, body mass index, smoking status, timing of intercourse, parity, education, number of sexual partners, and household income. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with no lesion, the adjusted FRs (95% CI) for the association between CIN and fecundability were: other cervical lesions, 0.97 (0.91-1.04); CIN1, 1.04 (0.96-1.13); CIN2+ no surgery, 1.00 (0.82-1.22); and CIN2+ with surgery 0.99 (0.89-1.10). The FRs (95% CI) for a recent diagnosis (<2 years) of CIN were 0.98 (0.86-1.11) for other cervical lesions; 1.13 (0.99-1.29) for CIN1; 0.89 (0.62-1.26) for CIN2+ no surgery and 0.91 (0.75-1.10) for CIN2+ with surgery compared with the no lesion group. LIMITATIONS, REASONS FOR CAUTION: In the analyses, we adjusted for several covariates related to the women. However, we had little information on the male partners which could lead to unmeasured confounding as fecundability is a couple-based measure of fertility. Furthermore, a CIN diagnosis may not be constant as it may regress or progress spontaneously; therefore, it is possible that we have misclassified some women, especially women categorized as having normal cells or CIN1. WIDER IMPLICATIONS OF THE FINDINGS: Our results contribute important knowledge to women who are concerned about their future fertility after receiving a CIN diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Danish Cancer Society (R167-A11036-17-S2). The overall cohorts were funded by the National Institute of Child Health and Human Development (R01-HD086742 and R03-HD094117). The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Exposure to residential greenness, perceived stress, and depressive symptoms in a North American preconception cohort.

BACKGROUND: Studies suggest that greater exposure to natural vegetation (i.e., greenness) is associated with better mental health. However, there is limited research on greenness and mental health in the preconception period, a critical window of exposure in the life course. We investigated the associations of residential greenness with perceived stress and depressive symptoms using cross-sectional data from a cohort of pregnancy planners. METHODS: From 2013 to 2019, we enrolled female-identified participants aged 21-45 years who were trying to conceive without the use of fertility treatment into a North American preconception cohort study (Pregnancy Study Online [PRESTO]). On the baseline questionnaire, participants completed the 10-item Perceived Stress Scale (PSS) and the Major Depression Inventory (MDI). Using geocoded addresses, we estimated residential greenness exposure via satellite imagery (Normalized Difference Vegetation Index [NDVI]) in a 100m buffer. We estimated mean differences and 95% confidence intervals for the association of greenness with perceived stress and depression scores using linear regression models, adjusting for individual and neighborhood sociodemographic characteristics. We also evaluated the extent to which associations were modified by urbanicity and neighborhood socioeconomic status (SES). RESULTS: Among 9718 participants, mean age was 29.9 years, 81.5% identified as non-Hispanic White, 25% had household incomes <$50,000, and mean neighborhood income was $61,932. In adjusted models, higher greenness was associated with lower stress and depression scores (mean difference per interquartile range in greenness: -0.20, 95% CI: -0.39, -0.01; and -0.19, 95% CI: -0.48, 0.10, respectively). The association was stronger among residents of lower SES neighborhoods in urban areas (PSS: -0.57, 95% CI: -1.00, -0.15; MDI: -0.72, 95% CI: -1.40, -0.04). CONCLUSIONS: Higher greenness exposure was associated with lower stress and depressive symptoms among pregnancy planners, particularly in lower-SES neighborhoods.

Hair product use and urinary biomarker concentrations of non-persistent endocrine disrupting chemicals among reproductive-aged Black women.

BACKGROUND: Studies have shown an association between hair product use and adverse health outcomes. Scientists have hypothesized that exposure to endocrine-disrupting chemicals (EDCs) drives these associations, but few studies have directly evaluated associations between hair product use and biomarkers of EDCs. Even more limited are studies of Black women, who frequently use EDC-containing products (e.g., hair relaxers). OBJECTIVE: We estimated associations between hair product use and EDC biomarker concentrations. METHODS: We leveraged cross-sectional data from the Study of Environment, Lifestyle, and Fibroids, a cohort of females aged 23-34 years who self-identified as Black/African American from the Detroit-metropolitan area (USA; n = 425). On structured questionnaires, participants reported their past 24-h and past 12-month use of hair products, including relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food. We quantified urinary concentrations of 19 phthalate/phthalate alternative metabolites, 7 phenols, and 4 parabens using high performance liquid chromatography isotope dilution tandem mass spectrometry. EDC biomarker concentrations were creatinine-adjusted and natural log-transformed. We used multivariable linear regression to estimate mean percent differences in EDC biomarker concentrations and 95% confidence intervals (CIs) associated with hair product use, adjusting for sociodemographic confounders. RESULTS: Hair product use was associated with greater concentrations of multiple EDC biomarkers. Notably, use of hair products in the previous 24 h (compared with non-use) was associated with 16.2% (95% CI = 0.7%, 35.9%), 35.0% (95% CI = 2.6%, 77.6%), and 32.3% (95% CI = 8.8%, 92.0%) higher concentrations of mono-isobutyl phthalate, methyl paraben, and ethyl paraben, respectively. Use of hair relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food in the past 12 months was also associated with higher concentrations of multiple phthalate, phenol, and paraben biomarkers. CONCLUSION: Hair product use was associated with higher biomarker concentrations of multiple phthalates, phenols, and parabens. These findings suggest that hair products are potentially important exposure sources for hormonally-active chemicals among Black women.

A Prospective Cohort Study of Persistent Endocrine Disrupting Chemicals and Perceived Stress.

Persistent endocrine disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants from the Study of Environment, Lifestyle and Fibroids (n=1,394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale (PSS-4) at baseline, and every 20 months through 60 months (range of scores: 0-16); higher scores indicated higher stress. EDCs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit Bayesian Kernel Machine Regression (BKMR) and linear mixed effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (e.g., PFDA, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, while other EDCs (e.g., PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women.

Childhood adversity and time-to-pregnancy in a preconception cohort.

We examined the association between childhood adversity and fecundability (the per-cycle probability of conception), and the extent to which childhood social support modified this association. We used data from 6,318 female participants aged 21-45 years in Pregnancy Study Online (PRESTO), a North American prospective preconception cohort study (2013-2022). Participants completed a baseline questionnaire, bimonthly follow-up questionnaires (until pregnancy or a censoring event), and a supplemental questionnaire on experiences across the life course including adverse childhood experiences (ACE) and social support (using the modified Berkman-Syme Social Network Index [SNI]). We used proportional probabilities regression models to compute fecundability ratios (FR) and 95% confidence intervals (CI), adjusting for potential confounders and precision variables. Adjusted FRs for ACE scores 1-3 and ≥4 vs. 0 were 0.91 (95% CI: 0.85, 0.97) and 0.84 (95% CI: 0.77, 0.91), respectively. FRs for ACE scores ≥4 vs. 0 were 0.86 (95% CI: 0.78, 0.94) among participants reporting high childhood social support (SNI ≥4) and 0.78 (95% CI: 0.56, 1.07) among participants reporting low childhood social support (SNI <4). Our findings confirm results from two previous studies and indicate that high childhood social support slightly buffered the effects of childhood adversity on fecundability.