Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study.

BACKGROUND: The timing of puberty may have an important impact on adolescent mental health. In particular, earlier age at menarche has been associated with elevated rates of depression in adolescents. Previous research suggests that this relationship may be causal, but replication and an investigation of whether this effect extends to other mental health domains is warranted. METHODS: In this Registered Report, we triangulated evidence from different causal inference methods using a new wave of data (N = 13,398) from the Norwegian Mother, Father, and Child Cohort Study. We combined multiple regression, one- and two-sample Mendelian randomisation (MR), and negative control analyses (using pre-pubertal symptoms as outcomes) to assess the causal links between age at menarche and different domains of adolescent mental health. RESULTS: Our results supported the hypothesis that earlier age at menarche is associated with elevated depressive symptoms in early adolescence based on multiple regression (ß = - 0.11, 95% CI [- 0.12, - 0.09], pone-tailed < 0.01). One-sample MR analyses suggested that this relationship may be causal (ß = - 0.07, 95% CI [- 0.13, 0.00], pone-tailed = 0.03), but the effect was small, corresponding to just a 0.06 standard deviation increase in depressive symptoms with each earlier year of menarche. There was also some evidence of a causal relationship with depression diagnoses during adolescence based on one-sample MR (OR = 0.74, 95% CI [0.54, 1.01], pone-tailed = 0.03), corresponding to a 29% increase in the odds of receiving a depression diagnosis with each earlier year of menarche. Negative control and two-sample MR sensitivity analyses were broadly consistent with this pattern of results. Multivariable MR analyses accounting for the genetic overlap between age at menarche and childhood body size provided some evidence of confounding. Meanwhile, we found little consistent evidence of effects on other domains of mental health after accounting for co-occurring depression and other confounding. CONCLUSIONS: We found evidence that age at menarche affected diagnoses of adolescent depression, but not other domains of mental health. Our findings suggest that earlier age at menarche is linked to problems in specific domains rather than adolescent mental health in general.

Child abuse and pubertal timing: what is the role of child sex and identity of the perpetrator?

BACKGROUND: This study investigated the association between child abuse [child neglect (CN), emotional (CEA) and physical abuse (CPA)] and early puberty with special regard to sex-specific effects concerning child and parental perpetrator. METHODS: Data assessment took place within the framework of the LIFE Child Depression study, a longitudinal study on the development of depressive symptoms and disorders between child- and adulthood in Leipzig, Germany. A sample of 709 children (8-14 years) was recruited from the general population and via psychiatric hospitals. Data on pubertal status were assessed using an instrument for self-assessment of tanner stages (scales of physical pubertal development). Information on menarche was provided by parents. The Parent-Child Conflict Tactics Scales (CTS-PC) served for data on child abuse. RESULTS: Regarding physical puberty markers, significant correlations were found, especially with child neglect (CN) and child emotional abuse (CEA). Regression analyses, controlling for Body-Mass-Index (BMI) and Socioeconomic Status (SES), revealed that children affected by child neglect perpetrated by mother (CNm) and child emotional abuse (CEA) parent-non-specifically enter puberty significantly earlier. Sex-specific analyses identified child neglect perpetrated by mother (CNm) to be associated with early puberty in girls and child emotional abuse perpetrated by father (CEAf) with early puberty in boys. Concerning the onset of menstruation, there was a significant positive correlation between early menarche and parent-specific and non-specific child neglect (CN), as well as between early menarche and child emotional abuse perpetrated by the mother (CEAm). In regression models that controlled for Body-Mass-Index (BMI) and Socioeconomic Status (SES) no significant associations were maintained. Child physical abuse (CPA) was not associated with early puberty. CONCLUSION: Results outlined child neglect (CN) and child emotional abuse (CEA) to be sex- and perpetrator-specific risk factors for early pubertal development. Knowledge of sex- and perpetrator-specific effects could help clinicians to specify their diagnostic process and to define differential prevention and treatment goals for children with experiences of CN and CEA. Further research on the sex-specific impact of parental CN and CEA on girls' and boys' puberty is needed.

Early age at menarche and history of sexually transmitted infections significantly predict cervical cancer screening uptake among women aged 25-49 years: evidence from the 2021 Côte d'Ivoire demographic and health survey.

INTRODUCTION: Cervical cancer is the second dominant type of cancer among Ivorian women with an estimated age-standardised incidence and mortality rate of 31.2 cases and 22.8 deaths per 100,000 women in 2020, respectively. The Ivorian government through its Ministry of Health implemented the National Cancer Control Programme (NCCP) in 2003 with the aim of improving the prevention, early detection and treatment of cancers in Côte d'Ivoire. Yet, there is a low uptake of CCS (1.2%). Thus, making CCS uptake an important public health concern in the country. Understanding of the extent to which reproductive factors predict CCS uptake is limited in literature. This study aimed to investigate reproductive factors as a predictor of women's uptake of CCS in Côte d'Ivoire. METHODS: Data from the 2021 Côte d'Ivoire Demographic and Health Survey. A sample of 9,078 women aged 25-49 years were analyzed. The outcome variable was CCS uptake while other variables considered included age at menarche, history of STI, sexual debut, parity, age, educational level, wealth index, health insurance, place of residence, and media exposure. A multivariable logistic regression model was fitted to examine the association between the outcome of interest and predictors at 95% confidence interval. RESULTS: Approximately, 7.52% of women aged 25-49 years had ever undergone testing for cervical cancer by a healthcare provider. Early menarche was associated with lower odds of CCS uptake [AOR = 0.78; CI = 0.65-0.95]. Compared to those who had no STI, women with a history of STI were more likely to screen for cervical cancer [AOR = 2.63; CI = 2.02-3.42]. Increasing age, higher educational attainment, having health insurance, and being exposed to media were significantly associated with CCS uptake. CONCLUSION: In Cote d'Ivoire, age at menarche and STI history constitute reproductive factors that were significantly associated with women's uptake of CCS. It is imperative for public policy to focus on increasing CCS in these higher-risk women (i.e., women who experienced early menarche, women with early sexual debut and higher parity) through increased sensitization on cervical cancer risk factors.

Genetic correlation and Mendelian randomization analyses support causal relationships between dietary habits and age at menarche.

Dietary habits are essential in the mean age at menarche (AAM). However, the causal relationship between these factors remains unclear. Therefore, this study aimed to elucidate the genetic relationship between dietary habits and AAM. Genetic summary statistics for dietary habits were obtained from the UK Biobank. GWAS summary data for AAM was obtained from the ReproGen Consortium. Linkage disequilibrium score regression was used to test genetic correlations between dietary habits and AAM. The Mendelian randomization (MR) analyses used the inverse-variance weighted method. Genetic correlations with AAM were identified for 29 candi-date dietary habits, such as milk type (skimmed, semi-skimmed, full cream; coefficient = 0.2704, Pldsc = 1.13 × 10-14). MR evaluations revealed that 19 dietary habits were associated with AAM, including bread type (white vs. any other; OR 1.71, 95% CI 1.28-2.29, Pmr = 3.20 × 10-4), tablespoons of cooked vegetables (OR 0.437, 95% CI 0.29-0.67; Pmr = 1.30 × 10-4), and cups of coffee per day (OR 0.72, 95% CI 0.57-0.92, Pmr = 8.31 × 10-3). These results were observed to be stable under the sensitivity analysis. Our study provides potential insights into the genetic mechanisms underlying AAM and evidence that dietary habits are associated with AAM.

Protocol for the Adolescent Menstrual Experiences and Health Cohort (AMEHC) Study in Khulna, Bangladesh: A Prospective cohort to quantify the influence of menstrual health on adolescent girls' health and education outcomes.

BACKGROUND: Menstrual health is essential for gender equity and the well-being of women and girls. Qualitative research has described the burden of poor menstrual health on health and education; however, these impacts have not been quantified, curtailing investment. The Adolescent Menstrual Experiences and Health Cohort (AMEHC) Study aims to describe menstrual health and its trajectories across adolescence, and quantify the relationships between menstrual health and girls' health and education in Khulna, Bangladesh. METHODS AND ANALYSIS: AMEHC is a prospective longitudinal cohort of 2016 adolescent girls recruited at the commencement of class 6 (secondary school, mean age=12) across 101 schools selected through a proportional random sampling approach. Each year, the cohort will be asked to complete a survey capturing (1) girls' menstrual health and experiences, (2) support for menstrual health, and (3) health and education outcomes. Survey questions were refined through qualitative research, cognitive interviews and pilot survey in the year preceding the cohort. Girls' guardians will be surveyed at baseline and wave 2 to capture their perspectives and household demographics. Annual assessments will capture schools' water, sanitation and hygiene, and support for menstruation and collect data on participants' education, including school attendance and performance (in maths, literacy). Cohort enrolment and baseline survey commenced in February 2023. Follow-up waves are scheduled for 2024, 2025 and 2026, with plans for extension. A nested subcohort will follow 406 post-menarche girls at 2-month intervals throughout 2023 (May, August, October) to describe changes across menstrual periods. This protocol outlines a priori hypotheses regarding the impacts of menstrual health to be tested through the cohort. ETHICS AND DISSEMINATION: AMEHC has ethical approval from the Alfred Hospital Ethics Committee (369/22) and BRAC James P Grant School of Public Health Institutional Review Board (IRB-06 July 22-024). Study materials and outputs will be available open access through peer-reviewed publication and study web pages.

Age at menarche and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study.

BACKGROUND: Sex difference in the incidence rate of idiopathic pulmonary fibrosis (IPF) indicates that estrogen has a certain protective effect on the disease. Nevertheless, there is a dearth of study investigating the association between factors pertaining to endogenous estrogen exposure level, such as age at menarche (AAM) in women, and IPF. Our study intended to employ Mendelian randomization (MR) method to elucidate the causal association between AAM and IPF. METHODS: Our study utilized AAM as a measure of endogenous estrogen exposure and investigated its causal effect on the risk of IPF through MR. We employed the inverse variance weighted (IVW) method to assess the causal relationship between AAM and IPF risk, with supplementary analyses conducted using the weighted median estimator (WME) and MR-Egger method. Several sensitivity analyses were performed to assess the dependability of MR estimates. RESULTS: A total of 9 selected single nucleotide polymorphisms (SNPs) significantly associated with AAM were selected as instrumental variables. The IVW method showed that genetically later AAM was associated with an increased risk of IPF (odds ratio [OR] = 1.0014, 95%confidence interval [CI] = 1.0005-1.0023, p = 0.001). The median weighting method and the MR-Egger method obtained similar estimates, and no heterogeneity or pleiotropy was found, indicating that the results were robust. CONCLUSIONS: Our MR study suggested a causal relationship between a later onset of menarche and a heightened susceptibility to IPF.

Breast composition during and after puberty: the Chilean Growth and Obesity Cohort Study.

BACKGROUND: Breast density (BD) is a strong risk factor for breast cancer. Little is known about how BD develops during puberty. Understanding BD trajectories during puberty and its determinants could be crucial for promoting preventive actions against breast cancer (BC) at early ages. The objective of this research is to characterize % fibroglandular volume (%FGV), absolute fibroglandular volume (AFGV), and breast volume (BV) at different breast Tanner stages until 4-year post menarche in a Latino cohort and to assess determinants of high %FGV and AFGV during puberty and in a fully mature breast. METHODS: This is a longitudinal follow-up of 509 girls from low-middle socioeconomic status of the Southeast area of Santiago, recruited at a mean age of 3.5 years. The inclusion criteria were singleton birth born, birthweight between 2500 and 4500 g with no medical or mental disorder. A trained dietitian measured weight and height since 3.5 years old and sexual maturation from 8 years old (breast Tanner stages and age at menarche onset). Using standardized methods, BD was measured using dual-energy X-ray absorptiometry (DXA) in various developmental periods (breast Tanner stage B1 until 4 years after menarche onset). RESULTS: In the 509 girls, we collected 1,442 breast DXA scans; the mean age at Tanner B4 was 11.3 years. %FGV increased across breast Tanner stages and peaked 250 days after menarche. AFGV and BV peaked 2 years after menarche onset. Girls in the highest quartiles of %FGV, AFGV, and BV at Tanner B4 and B5 before menarche onset had the highest values thereafter until 4 years after menarche onset. The most important determinants of %FGV and AFGV variability were BMI z-score (R2 = 44%) and time since menarche (R2 = 42%), respectively. CONCLUSION: We characterize the breast development during puberty, a critical window of susceptibility. Although the onset of menarche is a key milestone for breast development, we observed that girls in the highest quartiles of %FGV and AFGV tracked in that group afterwards. Following these participants in adulthood would be of interest to understand the changes in breast composition during this period and its potential link with BC risk.

Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk.

We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)-control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (logistic/model-based multifactor dimensionality reduction [MB-MDR]) with subsequent in silico assessment of the assumed functionality pithy of FGR-related loci. Three mAAM-appertain loci were FGR-linked to genes such as KISS1 (rs7538038) (effect allele G-odds ratio (OR)allelic = 0.63/pperm = 0.0003; ORadditive = 0.61/pperm = 0.001; ORdominant = 0.56/pperm = 0.001), NKX2-1 (rs999460) (effect allele A-ORallelic = 1.37/pperm = 0.003; ORadditive = 1.45/pperm = 0.002; ORrecessive = 2.41/pperm = 0.0002), GPRC5B (rs12444979) (effect allele T-ORallelic = 1.67/pperm = 0.0003; ORdominant = 1.59/pperm = 0.011; ORadditive = 1.56/pperm = 0.009). The haplotype ACA FSHB gene (rs555621*rs11031010*rs1782507) was FRG-correlated (OR = 0.71/pperm = 0.05). Ten FGR-implicated interworking models were founded for 13 SNPs (pperm ≤ 0.001). The rs999460 NKX2-1 and rs12444979 GPRC5B interplays significantly influenced the FGR risk (these SNPs were present in 50% of models). FGR-related mAAM-appertain 15 polymorphic variants and 350 linked SNPs were functionally momentous in relation to 39 genes participating in the regulation of hormone levels, the ovulation cycle process, male gonad development and vitamin D metabolism. Thus, this study showed, for the first time, that the mAAM-appertain genes determine FGR risk.

Menstrual health and hygiene knowledge among post menarche adolescent school girls in urban and rural Tanzania.

Adolescent girls' capacity to lead healthy lives and perform well in school has been hampered by their lack of awareness about menstruation and the requirements for its hygienic management. Lack of enabling infrastructure, improper menstrual supplies, and limited socioeconomic support for good menstrual health and cleanliness are characteristics of schools in Africa South of the Sahara. We evaluated school-age girls' knowledge of menstrual hygiene and identified bottlenecks that could affect policy and programming for menstrual health and hygiene. A school-based cross-sectional study involved 8,012 adolescent school girls in the age group of 11-18 years (mean age = 14.9 years). The study evaluated students' knowledge of menstrual health and hygiene (MHH) from the viewpoints of schools and communities using a combination of qualitative and quantitative approaches. Data was collected using self-administered surveys, focus group discussions, in-depth interviews, and site observations. Girls' older age (AOR = 1.62, P 0.001), having a female guardian (AOR = 1.39: P = 001), and having a parent in a formal job (AOR = 1.03: P 0.023) were positively associated with Menstrual health and Hygiene Knowledge. MHH knowledge levels varied significantly between girls attending government (53.3) and non-government schools (50.5%, P = 0.0001), although they were comparable for girls attending rural and urban schools. Only 21% of the study's schools had at least one instructor who had received training in MHH instruction for students. We have established that the majority of adolescent girls in schools have inadequate knowledge on menstrual health and hygiene, and that school teachers lack the skills to prepare and support young adolescents as they transition into puberty. Concerted actions aimed at building supportive policy are paramount, for school-aged teenagers to learn about and reap the long-term advantages of good menstrual health practices.

Crecimiento y desarrollo puberal en niñas adoptadas de Rusia: seguimiento de 12 años / Growth and pubertal development in girls adopted from Russia: 12-year follow-up

Introducción: los objetivos fueron aportar datos de la evolución longitudinal del crecimiento y determinar la edad de la telarquia y menarquia en niñas adoptadas de Rusia. Material y métodos: estudio de cohorte prospectivo sobre 24 niñas rusas adoptadas en España entre 2002-2010 controladas durante doce años. Se recopilaron antecedentes adversos revisando los informes médicos preadoptivos. Se registraron estandarizadamente: peso, talla, perímetro cefálico y edad de la telarquia y menarquia. Los valores medios se compararon con estándares de referencia. Resultados: antecedentes principales: pretérmino (33,3%), bajo peso al nacer (41,7%), exposición prenatal al alcohol (45,8%), abuso/negligencia (54,2%). Evaluación inicial: edad media (DE), 3 (1,6) años; puntuación Z (pZ) peso, -1,35; pZ talla, -2,42; pZ perímetro cefálico, -1,77. Tras 1 año de la adopción, se observó crecimiento recuperador significativo del peso (pZ +0,68), talla (pZ +0,98) y perímetro cefálico (pZ +0,76). Tendencias temporales del crecimiento: no se observó retraso del peso desde los 7 años; la talla mantuvo recuperación hasta los 10 años (pZ -0,40) y se mantuvo estable hasta los 15 años (pZ -0,46); el grado de retraso de la talla siempre fue superior al del peso. Aparición de la telarquia: edad media (DE), 9,9 (0,8) años; talla 135,4 cm (pZ -0,43). Presentación de la menarquia: edad media (DE), 11,9 (0,7) años; talla 147,6 cm (pZ -0,44). Conclusiones: el patrón de crecimiento y desarrollo se caracterizó por un retraso severo de la talla y moderado del peso y perímetro cefálico en el momento de la adopción, un rápido, significativo y prolongado crecimiento recuperador, una aceleración del desarrollo puberal con telarquia y menarquia tempranas, y una incompleta recuperación de la talla. (AU)

Introduction: the objectives were to provide longitudinal data on growth and determine the age of thelarche and menarche in girls adopted from Russia. Material and methods: prospective cohort study in 24 girls from Russia adopted in Spain in the 2002-2010 period, who were followed up for 12 years. The history of adverse childhood experiences was collected by reviewing pre-adoption medical records. We recorded standardised measurements of weight, height and head circumference and the age at thelarche and menarche. The mean values were compared with reference standards. Results: Salient history: preterm birth (33.3%), low birth weight (41.7%), prenatal alcohol exposure (45.8%), abuse and neglect (54.2%). Initial evaluation: mean age, 3 years (standard deviation [SD] 1.6) years; weight z-score (z), −1.35; height z, −2.42; head circumference z −1.77. One year after adoption, there was significant catch-up growth in weight (z +0.68), height (z +0.98), and head circumference (z +0.76). Temporal trends in growth: no weight delay from age 7 years; height continued to recover until age 10 (z −0.40) and remained stable until age 15 (z −0.46); the delay was greater compared to weight at every timepoint. The mean age at onset of thelarche was 9.9 years (SD 0.8) with a height of 135.4 cm (z −0.43). The mean age at menarche was 11.9 years (SD 0.7) years, with a height of 147.6 cm (z −0.44). Conclusions: the pattern of growth and development was characterized by severe delay in linear growth and a moderate delay in weight and head circumference at the time of adoption, rapid, significant and prolonged catch-up growth, acceleration of pubertal development with early thelarche and menarche and an incomplete recovery of linear growth. (AU)

Menarche, pubertal timing and the brain: female-specific patterns of brain maturation beyond age-related development.

BACKGROUND: Puberty depicts a period of profound and multifactorial changes ranging from social to biological factors. While brain development in youths has been studied mostly from an age perspective, recent evidence suggests that pubertal measures may be more sensitive to study adolescent neurodevelopment, however, studies on pubertal timing in relation to brain development are still scarce. METHODS: We investigated if pre- vs. post-menarche status can be classified using machine learning on cortical and subcortical structural magnetic resonance imaging (MRI) data from strictly age-matched adolescent females from the Adolescent Brain Cognitive Development (ABCD) cohort. For comparison of the identified menarche-related patterns to age-related patterns of neurodevelopment, we trained a brain age prediction model on data from the Philadelphia Neurodevelopmental Cohort and applied it to the same ABCD data, yielding differences between predicted and chronological age referred to as brain age gaps. We tested the sensitivity of both these frameworks to measures of pubertal maturation, specifically age at menarche and puberty status. RESULTS: The machine learning model achieved moderate but statistically significant accuracy in the menarche classification task, yielding for each subject a class probability ranging from 0 (pre-) to 1 (post- menarche). Comparison to brain age predictions revealed shared and distinct patterns of neurodevelopment captured by both approaches. Continuous menarche class probabilities were positively associated with brain age gaps, but only the menarche class probabilities-not the brain age gaps-were associated with age at menarche. CONCLUSIONS: This study demonstrates the use of a machine learning model to classify menarche status from structural MRI data while accounting for age-related neurodevelopment. Given its sensitivity towards measures of puberty timing, our work suggests that menarche class probabilities may be developed toward an objective brain-based marker of pubertal development.

Puberty is a period of substantial changes in the life of youths, and these include profound brain changes. Most studies have investigated age related changes in brain development, recent work however suggests that looking at brain development through the lens of pubertal development can provide additional insights beyond age effects. We here analyzed brain imaging data from a group of same-aged adolescent girls from the Adolescent Brain Cognitive Development study. Our goal was to investigate if we could determine from brain images whether a girl had started her menstrual period (menarche) or not, and we used machine learning to classify between them. This machine learning model does not just return a "yes/no" decision, but also returns a number between 0 and 1 indicating a probability to be pre- (0) or post- (1) menarche. To rule out that our approach only maps age-related development, we selected a strictly age-matched sample of girls and compared our classification model to a brain age model trained on independent individuals. Our model classified between pre- and post-menarche with moderate accuracy. The obtained class probability was partly related to age-related brain development, but only the probability was significantly associated with pubertal timing (age at menarche). In summary, our study uses a machine learning model to estimate whether a girl has reached menarche based on her brain structure. This approach offers new insights into the connection between puberty and brain development and might serve as an objective way to assess pubertal timing from imaging data.

Pubertal timing: A life course pathway linking early life risk to adulthood cardiometabolic health.

OBJECTIVE: To evaluate a series of prospective life course models testing whether the timing of pubertal development is a pathway through which prepubertal risk factors may influence adulthood cardiometabolic health. METHODS: Subjects were 655 female participants in the NICHD Study of Early Child Care and Youth Development (SECCYD) and recent SECCYD 30-year follow-up, the Study of Health in Early and Adult Life (SHINE). Prepubertal risk factors included maternal menarcheal age, child race/ethnicity, child health status indicators, and child adversity indicators. Pubertal timing was indexed by breast development onset (Tanner stage [TS] II), pubic hair onset (TS II) and menarcheal age. Adulthood cardiometabolic risk (CMR) was indexed by a composite of waist circumference, systolic blood pressure, diastolic blood pressure, hemoglobin A1c, C-reactive protein, and high-density lipoprotein. RESULTS: Inspection of paths between the prepubertal risk factors, pubertal timing indicators, and adulthood CMR composite showed later breast development onset (-0.173, p < .01), later pubic hair onset (-0.182, p < .01), and later menarche (-0.145, p < .01) each predicted lower adulthood CMR, and each pubertal timing indicator mediated effects of prepubertal risk factors on adulthood CMR. Specifically, the timing of breast development onset and menarche mediated effects of maternal menarcheal age, Black (vs. White), Asian/PI (vs. White), child BMI percentile, and child SES on adulthood CMR (all ps < .05), and the timing of pubic hair onset mediated effects of maternal menarcheal age, Black (vs. White), and child BMI percentile on adulthood CMR (all ps < .10). CONCLUSION: Findings in the current study contribute to the broader literature by identifying pubertal development and its timing as a potentially important pathway through which early life exposures may shape adulthood cardiometabolic health and disease. These findings have important implications for novel opportunities for increased surveillance and potential intervention focusing on pubertal development as a target to improve health more broadly.

Long-term exposure to ambient PM2.5 and its components on menarche timing among Chinese adolescents: evidence from a representative nationwide cohort.

BACKGROUND: Ambient air pollutants have been suggested to affect pubertal development. Nevertheless, current studies indicate inconsistent effects of these pollutants, causing precocious or delayed puberty onset. This study aimed to explore the associations between long-term exposure to particulate matter with aerodynamic diameters ≤ 2.5 µm (PM2.5) along with its components and menarche timing among Chinese girls. METHOD: Self-reported age at menarche was collected among 855 girls from China Health and Nutrition Survey 2004 to 2015. The pre-menarche annual average concentrations of PM2.5 and its components were calculated on the basis of a long-term (2000-2014) high-resolution PM2.5 components dataset. Generalized linear models (GLM) and logistic regression models were used to analyze the associations of exposure to a single pollutant (PM2.5, sulfate, nitrate, ammonium, black carbon and organic matter) with age at menarche and early menarche (< 12 years), respectively. Weighted quantile sum methods were applied to examine the impacts of joint exposure on menarche timing. RESULTS: In the adjusted GLM, per 1 µg/m3 increase of annual average concentrations of nitrate and ammonium decreased age at menarche by 0.098 years and 0.127 years, respectively (all P < 0.05). Every 1 µg/m3 increase of annual average concentrations of PM2.5 (OR: 1.04, 95% CI: 1.00-1.08), sulfate (OR: 1.23, 95% CI: 1.01-1.50), nitrate (OR: 1.23, 95% CI: 1.06-1.43) and ammonium (OR: 1.32, 95% CI: 1.06-1.66) were significantly positively associated with early menarche. Higher level of joint exposure to PM2.5 and its components was associated with 11% higher odds of early menarche (P = 0.04). Additionally, the estimated weight of sulfate was the largest among the mixed pollutants. CONCLUSIONS: Long-term exposure to PM2.5 and its components could increase the risk of early menarche among Chinese girls. Moreover, sulfate might be the most critical components responsible for this relationship. Our study provides foundation for targeted prevention of PM2.5 components.

Anterior knee laxity is greater in athletic females who attain menarche at a younger age.

PURPOSE: Females with above-average anterior knee laxity values are at increased risk of anterior cruciate ligament (ACL) injury. The purpose of this study was to examine the effects of menarche age (MA) and menarche offset on anterior knee laxity in young, physically active women. METHODS: Anterior knee laxity (KT-2000) and menstrual characteristics (per self-report) were recorded in 686 Slovenian sportswomen from team handball, volleyball and basketball club sports (average years sport participation: 7.3 ± 3.6 years). Females were stratified into four groups based on their self-reported age at menarche: 9-11, 12, 13 and 14+ years. Anterior knee laxity was compared across MA groups using a univariate analysis of variance (ANOVA) with Bonferroni correction, with and without controlling for factors that could potentially differ between groups and influence anterior knee laxity. Females were then stratified into four groups based on the number of years they were away from their age at onset of menarche. Groups were compared using a univariate ANOVA with Bonferroni correction, with and without controlling for factors that differed between groups and could influence anterior knee laxity. RESULTS: Anterior knee laxity was greater in females who attained menarche at 12 years of age (6.4 ± 1.5 mm) or younger (6.6 ± 1.6 mm) compared to 14 years of age or older (5.8 ± 1.2 mm) (p < 0.001; partial η2 = 0.032). Anterior knee laxity was 0.7-1.4 mm greater in females who were 5 or more years away from menarche compared to those who were within 2 years of menarche (5.8 ± 1.3 mm; p < 0.001). CONCLUSION: Anterior knee laxity is greater in females who attained menarche at a younger age and in females who are 5 or more years postmenarche. Age of menarche represents a critical pubertal event that is easy for women to recall and may provide important insights into factors that moderate anterior knee laxity, a risk factor for ACL injury in women. LEVEL OF EVIDENCE: Level IV.

Secular trend in age at menarche among Indian women.

Age at menarche is not only a parameter that signifies biological characteristics for women but is also considered as an indicator to measure the quality of life of a population. Moreover, menarche has significant implications on women's health and information about menarcheal age is crucial for health policymakers. However, little is known about the trends in menarcheal age in India. Thus, in order to fill this research gap, the present study aimed to explore the age at menarche, its trend and regional heterogeneity among Indian women. A birth cohort approach was used by polling data from the 1st (1992-93), 4th (2015-16) and 5th (2019-21) rounds of NFHS. Descriptive statistics and bivariate analyses were performed to present the distribution of age at menarche and mean age at menarche across birth cohorts and each category of covariates. A multiple linear regression model was fitted to examine the trend in age at menarche and further to investigate the association of covariates with menarcheal age among Indian women. The analysis demonstrated that a majority of women (66.2%) attained menarche between the ages of 13-14 years. Moreover, about 17.2% of women experienced an early age at menarche, whereas 16.7% of women had a late age at menarche. The mean age at menarche for the sampled women was 13.49 years. The analysis also observed a secular declining trend in menarcheal age among Indian women and a significant variation in the mean age at menarche across birth cohorts. It also highlighted significant socio-economic patterning in menarcheal age among women.

Dysmenorrhea pattern in adolescences informing adult endometriosis.

BACKGROUND: Endometriosis (EMs) is a chronic and progressive disease that, if diagnosed late, can lead to infertility and deep infiltrating endometriosis (DIE). Dysmenorrhea is the most prominent symptom of EMs. However, limited research exists on the specific correlation between dysmenorrhea patterns and EMs. Early prevention of EMs is essential to effectively manage the progression of the disease, and is best detected during adolescence. Our objective was to associate the development of EMs with dysmenorrhea patterns during adolescence and quantify the risk of adult EMs for adolescent girls, with the aim of supporting primary intervention strategy planning. METHODS: This case-control study examined predictors for adult EMs based on dysmenorrhea patterns in adolescents. We collected 1,287 cases of 641 EMs and 646 healthy females regarding their basic demographic information, adolescent menstrual characteristics, adolescent dysmenorrheal patterns, and adolescent lifestyles. Age-matching (1-to-1) was employed to control for the confounding effect of age between the groups. Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression models were utilized to identify predictors for adult EMs. The predictive value of the model was evaluated using the area under the receiver operating characteristic curve (AUC) and the C-index, while Hosmer-Lemeshow Test assessed the goodness of fit of the model. Data from one additional cohort in Shenzhen hospitalized with EMs were used to external validation were analyzed. RESULTS: Individuals who always experienced dysmenorrhea had a risk of adult endometriosis 18.874 (OR = 18.874; 95%CI = 10.309-34.555) times higher than those occasional dysmenorrhea, The risk of developing EMs was 5.257 times higher in those who experienced dysmenorrhea more than 12 months after menarche than in those who experienced dysmenorrhea less than 6 months after menarche (OR = 5.257, 95% CI = 3.343-8.266), AUC in the external validation cohort was 0.794(95%CI: 0.741-0.847). We further found that high-intensity physical activity and sun-sensitive skin of burning were influential factors in high-frequency dysmenorrhea. The AUC value for the internal evaluation of the model was 0.812 and the AUC value for the external validation was 0.794. CONCLUSION: Our findings revealed that the frequency of dysmenorrhea during adolescence contributed to the development of adult endometriosis. The frequency and onset of dysmenorrhea in adolescence were promising predictors for adult EMs. Both internal and external validation proved the model's good predictive ability. TRIAL REGISTRATION: http://www.chictr.org.cn/ , TRN: ChicTR2200060429, date of registration: 2022/06/01, retrospectively registered.

The causal effects of age at menarche and age at menopause on sepsis: A two-sample Mendelian randomization analysis.

OBJECTIVES: To determine whether the age at menarche (AAM) and the age at menopause (ANM) are causally related to the development of sepsis. METHODS: We performed a two-sample Mendelian randomization (MR) analysis by utilizing summary statistics from genome-wide association study (GWAS) datasets for both the exposure and outcome variables. Single nucleotide polymorphisms (SNPs) that exhibited significant associations with AAM and ANM were chosen as instrumental variables to estimate the causal effects on sepsis. Our study employed a variety of methods, including MR-Egger regression, weighted median estimation, inverse variance weighting, a simple model, and a weighted model. Odds ratios (ORs) along with their corresponding 95% confidence intervals (CIs) were used as the primary indicators for assessing causality. Furthermore, we conducted sensitivity analyses to explore the presence of genetic heterogeneity and validate the robustness of the tools employed. RESULT: Our analysis revealed a significant negative causal relationship between AAM and the risk of sepsis (IVW: OR = 0.870, 95% CI = 0.793-0.955, P = 0.003). However, our Mendelian randomization (MR) analysis did not yield sufficient evidence to support a causal link between ANM and sepsis (IVW: OR = 0.987, 95% CI = 0.971-1.004, P = 0.129). CONCLUSIONS: Our findings suggest that an earlier AAM may be associated with an increased risk of sepsis. However, we did not find sufficient evidence to support a causal relationship between ANM and sepsis.

Early or late menarche is associated with reduced fecundability in the Norwegian Mother, Father and Child Cohort Study.

STUDY QUESTION: Is age at menarche associated with fecundability? SUMMARY ANSWER: Both early (<11 years) and late (>15 years) menarche is associated with decreased fecundability. WHAT IS KNOWN ALREADY: Previous studies on age at menarche and fecundability have been inconclusive. Women with early or late menarche are at increased risks of gynaecological and autoimmune diseases that may affect their ability to conceive. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study including 67 613 pregnant women, participating in the Norwegian Mother, Father and Child Cohort Study between 1999 and 2008, with self-reported information on age at menarche and time to pregnancy. We included planned pregnancies that were conceived either naturally or with the help of assisted reproductive technologies. PARTICIPANTS/MATERIALS, SETTING, METHODS: We calculated fecundability ratios (FRs) with 95% CIs representing the cycle-specific probability of conception by categories of age at menarche. FRs were adjusted for participants' pre-pregnancy body mass index, highest completed or ongoing education level, and age at initiation of trying to conceive. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a 7% lower probability of conceiving during any given menstrual cycle up to 12 cycles in women with early or late menarche. Among women with menarche >15 years, the adjusted FR was 0.93 (95% CI: 0.90-0.97), and among women with menarche <11 years, the adjusted FR was 0.93 (95% CI: 0.89-0.99), when compared to women with menarche between 12 and 14 years. LIMITATIONS, REASONS FOR CAUTION: The study-population consisted of women pregnant in their second trimester, excluding those with persistent infertility. Recall of age at menarche and time to pregnancy may be inaccurate. WIDER IMPLICATIONS OF THE FINDINGS: Both early (<11 years) and late (>15 years) menarche was associated with decreased fecundability. Women experiencing early menarche or late menarche may be counselled accordingly. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Norwegian Institute of Public Health, Oslo, Norway, and by Telemark Hospital Trust, Porsgrunn, Norway and was partly supported by the Research Council of Norway through its centres of excellence funding scheme (project number 262700) and the Research Council of Norway (project no. 320656). The project was co-funded by the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them. M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 947684). The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The impact of reproductive factors on the metabolic profile of females from menarche to menopause.

We explore the relation between age at menarche, parity and age at natural menopause with 249 metabolic traits in over 65,000 UK Biobank women using multivariable regression, Mendelian randomization and negative control (parity only). Older age of menarche is related to a less atherogenic metabolic profile in multivariable regression and Mendelian randomization, which is largely attenuated when accounting for adult body mass index. In multivariable regression, higher parity relates to more particles and lipids in VLDL, which are not observed in male negative controls. In multivariable regression and Mendelian randomization, older age at natural menopause is related to lower concentrations of inflammation markers, but we observe inconsistent results for LDL-related traits due to chronological age-specific effects. For example, older age at menopause is related to lower LDL-cholesterol in younger women but slightly higher in older women. Our findings support a role of reproductive traits on later life metabolic profile and provide insights into identifying novel markers for the prevention of adverse cardiometabolic outcomes in women.

The impact of menarche on hippocampal mechanisms of severity of psychotic-like experiences in the ABCD study.

Accumulating evidence suggests that estrogens play an important modulatory role in the pathogenesis of psychosis. Estrogens come online within a dynamic developmental context of emerging psychopathology and neurodevelopment. As a result, estradiol (the primary form of estrogen) may influence psychosis lability directly or indirectly through its neurodevelopmental influence on estrogens-sensitive areas like the hippocampus. Understanding this influence may provide novel insight into mechanisms of psychosis lability. This study included baseline and year 2 timepoints from 4422 female participants from the Adolescent Brain Cognitive Development (ABCD) study (age 8-13), who varied in estradiol availability (pre-menarche, post-menarche, pre- and post-menarche timepoints). Estradiol availability was related to psychotic-like experiences (PLE) severity both directly and as an interactive effect with hippocampal connectivity using menarche status (pre/post) in a multilevel model. PLE severity was highest in individuals with early menarche emphasizing the importance of the developmental timing. Although PLE severity decreased over time in the sample, it stayed clinically-relevant over 2 years. Lower hippocampal connectivity was related to elevated PLE severity. This effect was moderated by estradiol; before the availability of estradiol (pre-menarche), lower hippocampal connectivity significantly contributed to the PLE severity, but when estradiol was available (post-menarche) hippocampal dysconnectivity did not account for PLE severity. This moderation suggests that the estrodiol's influence on hippocampal plasticity also reduced the mechanistic role of the hippocampus on PLE severity. Further, the lack of a significant direct reduction of PLE severity post-menarche, may suggest an increased role for other interacting psychosis lability factors during this critical developmental period.