MC3R links nutritional state to childhood growth and the timing of puberty.

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.

Female reproductive histories and the risk of chronic obstructive pulmonary disease.

BACKGROUND: Female reproductive factors may influence the development of chronic obstructive pulmonary disease (COPD) through the female hormonal environment, but studies on this topic are limited. This study aimed to assess whether age at menarche, number of children, infertility, miscarriage, stillbirth and age at natural menopause were associated with the risk of COPD. METHODS: Women from three cohorts with data on reproductive factors, COPD and covariates were included. Cause specific Cox regression models were adjusted for birth year, race, educational level, body mass index and pack years of smoking, stratified by asthma, and incorporating interaction between birth year and time. Between cohort differences and within cohort correlations were taken into account. RESULTS: Overall, 2 83 070 women were included and 10 737 (3.8%) developed COPD after a median follow-up of 11 (IQR 10-12) years. Analyses revealed a U shaped association between age at menarche and COPD (≤11 vs 13: HR 1.17, 95% CI 1.11 to 1.23; ≥16 vs 13: HR 1.24, 95% CI 1.21 to 1.27). Women with three or more children (3 vs 2: HR 1.14, 95% CI 1.12 to 1.17; ≥4 vs 2: HR 1.34, 95% CI 1.28 to 1.40), multiple miscarriages (2 vs 0: HR 1.28, 95% CI 1.24 to 1.32; ≥3 vs 0: HR 1.36, 95% CI 1.30 to 1.43) or stillbirth (1 vs 0: HR 1.38, 95% CI 1.25 to 1.53; ≥2 vs 0: HR 1.67, 95% CI 1.32 to 2.10) were at a higher risk of COPD. Among postmenopausal women, earlier age at natural menopause was associated with an increased risk of COPD (<40 vs 50-51: HR 1.69, 95% CI 1.63 to 1.75; 40-44 vs 50-51: HR 1.42, 95% CI 1.38 to 1.47). CONCLUSIONS: Multiple female reproductive factors, including age at menarche, number of children, miscarriage, stillbirth, and age at natural menopause were associated with the risk of COPD.

The association between reproductive history and abdominal adipose tissue among postmenopausal women: results from the Women's Health Initiative.

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.

Dynamics of body time, social time and life history at adolescence.

Recent opposing trends towards earlier physical maturation and later social maturation present a conundrum of apparent biological-social mismatch. Here we use life history analysis from evolutionary ecology to identify forces that drive these shifts. Together with findings in developmental science, our life history analysis indicates that adolescence is a distinctive period for biological embedding of culture. Ethnographic evidence shows that mass education is a novel feature of the globalizing cultural configurations of adolescence, which are driven by transformations in labour, livelihood and lifestyle. Evaluation of the life history trade-offs and sociocultural ecologies that are experienced by adolescents may offer a practical basis for enhancing their development.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

Self-reported history of breastfeeding in relation to recalled age at menarche in the United States.

Menarche is a key life history event that shapes the female reproductive trajectory and is important to the study of human biology because of the associated epidemiological and social consequences later in life. Our question is whether breastfeeding is associated with the variation in timing of menarche. Using data from a college-aged female student population from Amherst, MA, we examined whether having been breastfed was associated with age at menarche. Of the 340 female participants with information on breastfeeding during infancy, we found that women who were breastfed (n = 286) had an adjusted mean age of menarche of 12.53 years (SE 0.09), while those who were not breastfed (n = 54) had an adjusted mean age of menarche of 12.04 years (SE 0.20; p < 0.03). We propose further research that explores a finer distinction between formula-fed, mixed-fed or predominantly breastfed infants, duration of breastfeeding and age at menarche.

C-reactive protein (CRP) in high altitude Bolivian peri-urban adolescents varies by adiposity, current illness, height, socioeconomic status, sex, and menarcheal status: The potential benefits and costs of adipose reserves in arduous environments.

OBJECTIVES: In non-industrialized and low-income populations, adipose stores can serve as a valuable buffer against harsh conditions such as seasonal food scarcity. However, these reserves may incur costs due to adipocytes' production of pro-inflammatory cytokines; inflammation is associated with increased risk for cardiometabolic diseases later in life. Life history theory posits that, especially in populations with high juvenile mortality, higher adiposity may nonetheless be advantageous if its benefits in early life outweigh its later costs. Relatively little is known about adolescents' C-reactive protein concentration (CRP; an inflammation biomarker) in such environments. We investigated CRP and its associations with several hypothesized predictors in adolescents in an economically diverse peri-urban Andean community. METHODS: We measured CRP in dried blood spots and collected data on anthropometrics, illnesses, socioeconomic status (SES), and menarcheal status in 59 female and 40 male adolescents ("Alteños", 11.0-14.9 years old) with normal vital signs in El Alto, Bolivia (~4150 m amsl). We used Cole's LMS method to standardize all anthropometrics for sex and age, and principal components analysis to construct a "fat-factor" variable loading on these standardized z-scores. We used multiple linear regression to assess the influence of fat-factor and other likely predictors on CRP rank. RESULTS: Compared to a national Bolivian growth reference, Alteños were, on average, shorter and leaner; only 6% were classified as overweight and none were obese. Pre-menarche females were on average leaner than post-menarche females. The best-fitting model explained 24% of the variance in CRP rank. Significant predictors were fat-factor, SES, current illness for males and pre-menarche females, and z-height for females. CONCLUSIONS: Our results are consistent with a tradeoff between investments in growth versus immune functioning, as might be expected in an environment with limited resources and high pathogen exposure (e.g., soil-transmitted helminths, poor sanitation). Thinner Alteños appear to maintain a minimum CRP concentration independent of fat-factor, while fatter (or less-thin) Alteños' CRP rises with fat-factor. Female Alteños appear to be trading off investment in immune response for investment in growth and maturation. Alteños' high rate of stunting and absence of obesity suggests chronic, presumably multifactorial, stress. Adipose stores likely buffer against some of these stressors and, in an environment such as this-in which many lack sufficient nutritious foods, potable water, adequate sewage, and health care-may confer a net lifetime benefit.

OBJETIVOS: En poblaciones no industrializadas y de bajos ingresos, las reservas adiposas pueden servir como un valioso amortiguador frente a condiciones duras como la escasez estacional de alimentos. Sin embargo, estas reservas pueden tener un coste debido a la producción de citoquinas proinflamatorias por parte de los adipocitos; la inflamación se asocia a un mayor riesgo de enfermedades cardiometabólicas en etapas posteriores de la vida. La teoría de la historia vital postula que, especialmente en poblaciones con una elevada mortalidad juvenil, una mayor adiposidad puede ser ventajosa si sus beneficios en los primeros años de vida compensan sus costes posteriores. Se sabe relativamente poco sobre la concentración de proteína C reactiva (PCR; un biomarcador de inflamación) de los adolescentes. Investigamos la PCR y sus asociaciones con varios predictores hipotéticos en adolescentes de una comunidad andina periurbana económicamente diversa. MÉTODOS: Se midió la PCR en muestras de sangre seca y se recogieron datos sobre antropometría, enfermedades, nivel socioeconómico (NSE) y menarquia en 59 mujeres y 40 varones adolescentes («alteños¼, 11,0­14,9 años de edad) con signos vitales normales en El Alto, Bolivia (~4150m amsl). Usamos el método LMS de Cole para estandarizar todos los parámetros antropométricos para sexo y edad, y análisis de componentes principales para construir una variable «factor de grasa¼ cargada en estos puntajes z­estandarizados. Se utilizó la regresión lineal múltiple para evaluar la influencia del factor grasa y otros posibles predictores en el rango de la PCR. RESULTADOS: En comparación con una referencia nacional boliviana de crecimiento, los alteños eran, en promedio, más bajos y más delgados; sólo el 6% estaban clasificados con sobrepeso y ninguno era obeso. Las chicas premenárquicos eran, en promedio, más delgados que las chicas postmenárquicos. El modelo de regresión que mejor se ajustaba explicaba el 24% de la varianza en el rango de PCR. Observamos una nueva asociación entre la adiposidad y la PCR. Cuando el factor adiposidad es >0, el rango de la PCR aumenta linealmente con el factor adiposidad. Cuando el factor adiposidad es <0, la PCR no varía con el factor adiposidad. Estos patrones sugieren que los Alteños más delgados mantienen una concentración mínima de PCR independiente del factor adiposidad, mientras que la PCR de los Alteños más gordos (menos delgados) aumenta con el factor adiposidad. Además, existe una mayor variación en el rango de la PCR en los adolescentes más delgados que en los más gordos. El autoinforme de una enfermedad actual en niños y niñas premenárquicas se asoció con una PCR significativamente más alta. La ausencia de una asociación significativa entre la enfermedad actual y la PCR en las chicas postmenárquicas puede reflejar confusión por cambios en la PCR durante el ciclo menstrual. Manteniendo constantes todos los demás factores predictivos, la PCR aumentó con el incremento del nivel socioeconómico. En las niñas, el aumento de la estatura se asoció a una disminución de la PCR, lo que sugiere que las niñas favorecen la inversión en crecimiento y maduración frente a la inversión en respuestas inmunitarias inflamatorias a corto plazo. En los chicos, no se observó una relación significativa entre la estatura y la PCR. La baja estatura y la delgadez de estos adolescentes sugieren que pueden estar invirtiendo en defensas humorales a más largo plazo (por ejemplo, anticuerpos contra helmintos), pero esta hipótesis requiere más estudios. CONCLUSIONES: La alta tasa de retraso en el crecimiento y la ausencia de obesidad de los alteños sugieren un estrés crónico, presumiblemente multifactorial. Muchas familias carecen de alimentos nutritivos suficientes, agua potable, alcantarillado adecuado y atención sanitaria. Es probable que las reservas adiposas amortigüen algunos de estos factores de estrés y confieran un beneficio neto a lo largo de la vida (la reducción de la mortalidad juvenil puede compensar cualquier aumento del riesgo de enfermedades cardiometabólicas en etapas posteriores de la vida). Sin embargo, estas compensaciones tienen un coste para los individuos y las sociedades. Reducir los riesgos de patógenos y mejorar la capacidad de los habitantes del altiplano para acceder sistemáticamente a agua limpia y a alimentos sanos suficientes y asequibles probablemente reportaría beneficios para la salud a lo largo de toda la vida.

Association between age at menarche and cardiometabolic risk among Samoan adults.

OBJECTIVES: Recent studies suggest that early menarche may increase cardiometabolic morbidity and mortality. Yet few studies have examined this association in the Pacific Islands, where obesity prevalence is among the highest globally. We sought to examine associations between age at menarche and cardiometabolic risk in Samoa. METHODS: Participants were from the Soifua Manuia study (n = 285, age 32-72 years) conducted in Samoa from 2017 to 2019. Logistic regressions were conducted to estimate odds of obesity, hypertension, diabetes, dyslipidemia, and metabolic syndrome per one-year increase in age at menarche. Linear regressions were conducted to examine associations between age at menarche and continuous measures of adiposity, blood pressure, insulin resistance, and serum lipids. RESULTS: Median age at menarche was 14 years (IQR = 2). After controlling for relevant covariates, each one-year increase in age at menarche was associated with a 15% decrease (OR = 0.85, 95% CI: 0.72-1.01, p = .067) in odds of hypertension, but a 21% increase (OR = 1.21, 95% CI: 1.01-1.45, p = .044) in odds of diabetes and 18% increase (OR = 1.18, 95% CI: 0.98-1.42, p = .081) in odds of high total cholesterol. Each additional year in age at menarche was associated with a 1.60 ± 0.52 kg (p = .002) decrease in lean mass and 1.56 ± 0.51 kg (p = .003) decrease in fat-free mass. CONCLUSIONS: Associations between age at menarche and cardiometabolic risk may be population-specific and are likely influenced by both current and historical nutritional and epidemiological contexts. Prospective studies are needed to clarify the role of childhood adiposity and other early life exposures on age at menarche and subsequent cardiometabolic risk.

Associations between birthweight and preterm birth and the ages at menarche and menopause.

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 (ß) 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 ß=-0.361, SE = 0.09, P = < 0.001) and have a shorter reproductive window (adjusted ß = -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 ß=-0.506, SE = 0.16, P = 0.001) and have a shorter reproductive window (adjusted ß = -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.

Does timing of sexual debut following menarche among female youth in Uganda matter? A discrete time analysis.

BACKGROUND: The burden of early sexual engagement among youth is enormous. It directly raises the risk of sexually transmitted infections(STIs) and indirectly contributes to unintended pregnancy, unsafe abortion, premature childbirth, and psychosocial issues. The aim of this paper was to estimate the timing of sexual debut and examine the factors influencing the timing of first sexual intercourse following menarche among female youth aged between 15 and 24 in Uganda. METHOD: Self-reported data were extracted from the 2016 Uganda Demographic and Health Survey (UDHS), with a sub-sample of 7964 female youth from the individual woman file. Kaplan-Meier survival curves, decrement life-table analysis, and the discrete-time logit model were used to examine the timing of sexual debut and associated factors. RESULTS: 67.4% of the female youth had experienced first sexual initiation. Overall, the meantime to sexual debut was 4.4 years and the median time was 4.3 years, and all the female youth had experienced first sexual initiation by the end of the twelfth year following menarche. Significant factors found to influence the timing of sexual initiation include having higher education level (OR = 0.724: 95% CI = 0.59-0.89; p = 0.003), residing in the Northern region (OR = 0.877:95% CI = 0.79-0.97, p = 0.012), being employed (OR = 1.085: 95% CI = 1.01-1.16; p = 0.021), and being literate (OR = 1.155; 95% CI = 1.07-1.25; p < 0.001). CONCLUSIONS: These findings are expected to be central in the bid to delay first sexual intercourse. Also they shed light on some of the factors associated with the timing of sexual debut which may be addressed at community level for non-school going youth and in schools, as school based prevention sexual and reproductive health programs. The findings highlight the need for future studies to collect more data to explore further the linkage between time to first debut since menarche and, mass media, religion, type of residence, and wealth index.

Correlates of Menarcheal Age in a Psychiatric Sample of Adolescents.

ABSTRACT: Early pubertal timing is associated with more adverse childhood experiences (ACEs) and increased risk for psychopathology during adolescence. However, most work to date has used community or epidemiological samples, and it remains unclear whether these associations persist in acute clinical samples. The present study examined associations between age at menarche and ACEs, psychiatric symptoms, and emotion regulation difficulties in a sample of N = 140 adolescents on a psychiatric inpatient unit. Youth with early menarche reported higher levels of depressive symptoms, more severe suicidal ideation, and greater difficulty with emotion regulation than youth with normative age at menarche. There was a marginal effect of youth with early menarche reporting more ACEs and more anxiety symptoms. These results suggest menarcheal age, and ACEs may be useful risk factors to assess in inpatient settings to predict risk for more severe outcomes, and future research on pubertal timing in high acuity settings is warranted.

Menstrual pattern in polycystic ovary syndrome and hypothalamic-pituitary-ovarian axis immaturity in adolescents: a systematic review and meta-analysis.

OBJECTIVE: To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and Polycystic Ovary Syndrome (PCOS) through a systematic review and meta-analysis. METHODS: The PubMed, EMBASE, Web of Science, Virtual Health Library, Scopus databases were searched using combinations of descriptors. Study quality was assessed using the Newcastle-Ottawa Scale. For data analysis, the results were grouped into PCOS group and NPCOS group (HPO axis immaturity). We performed a meta-analysis of raw data and the inverse variance method, employing the standardized mean difference, of the age at menarche and BMI of adolescents. RESULTS: Participants totaled 1,718 from nine selected studies. The meta-analysis showed that the PCOS group had a higher BMI than the NPCOS group (SMD 0.334; CI95% 0.073 - 0.595; p = .012). The degree of heterogeneity of the studies was approximately 40%. No significant difference in age at menarche (SMD - 0.027; CI95% -0.227 - 0.172; p = 0.790) and menstrual patterns was found, but amenorrhea was described only in adolescents with PCOS. CONCLUSIONS: The main characteristic in menstrual pattern that differentiated PCOS patients from girls with HPO axis immaturity was amenorrhea. Also, the BMI of PCOS patients was nearly one third higher than that of adolescents with HPO axis immaturity.

Association of Age at Menarche with General and Abdominal Obesity in Young Women.

Background and Objectives: Age at menarche is related to various biological and socioeconomic factors in childhood. The aim of the study was to examine the association of age at menarche with general and abdominal obesity in young women. Materials and Methods: A transversal anthropometric survey was conducted with 102 females from 21 to 25 years of age. The surveyed traits included height, weight, waist circumference (WC) and hip circumference (HC). General obesity was assessed using the body mass index (BMI) and abdominal obesity by WC, waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). A retrospective method was used for collecting age at menarche data. Results: The average age at menarche is 12.80 years. Early menarcheal age (<12 years) is detected in 25.5% of young females, while late onset of menarche (>14 years) is recorded for 20.6% of subjects. Early menarche age subjects exhibit significantly higher BMI, WC and WHtR in comparison with their late menarche age peers. There is a significant negative correlation between BMI, WC and WHtR values and menarcheal age. Late age at menarche is associated with higher probability of underweight status (BMI < 18.5 and/or WHtR < 0.4). Conclusions: Age at menarche has a negative correlation with general and abdominal obesity. Young women with early age at menarche show statistically higher values of BMI, WC and WHtR, while those with late menarcheal age show greater susceptibility to becoming underweight.

Age at menarche and its association with blood pressure in adult women of developing countries: a systematic review and meta-analysis.

CONTEXT: Evidence about the effect of age at menarche (AAM) on blood pressure (BP) has largely been drawn from studies in developed countries. Studies in developing countries are expanding recently but have not been summarised. OBJECTIVE: To systematically explore the association between AAM and BP and the potential modifiers in developing countries. METHODS: We searched PubMed, Embase, and Web of Science for publications until March 2022. A random-effects model was used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). RESULTS: Twenty studies were eligible. In studies with participants' mean age at BP assessment <55 years, women in the oldest group as compared with the middle or the youngest group of AAM had a higher risk of hypertension in those studies without adjustment for confounders (RR 1.79, 95% CI 1.41-2.28, I2=97.0%), those with adjustment for confounders excluding adiposity (1.25,1.04-1.51, I2=84.8%), and those with adjustment for confounders including adiposity (1.38,1.03-1.86, I2=91.8%). In studies with participants' mean age at BP assessment ≥55 years, no significant differences were found for studies without adjustment for confounders (RR 1.07, 95% CI 0.78-1.47, I2=90.3%), studies with adjustment for confounders excluding adiposity (0.85, 0.78-0.92, I2=12.3%), or studies with adjustment for confounders including adiposity (0.95, 0.80-1.11, I2=45.5%). A similar association was observed between AAM and baseline systolic BP and diabolic BP. CONCLUSION: Late menarche was associated with a higher risk of BP and this association was modified by age and adiposity in developing countries.

Growth and Puberty Attainment of Girls with Human Immunodeficiency Virus.

SUMMARY: Pattern of physical growth and pubertal changes among 59 girls, aged 8-15 years, diagnosed as cases of HIV on anti-retroviral therapy was cross-sectionally studied. Besides, measurement of body weight, height, and body mass index, breast development stage, presence or absence of pubic and axillary hair, and age of attainment of menarche were also noted in these subjects in the growth clinic of the department. With the advancement of age, the weight and height of HIV girls increased; however, they were lighter and shorter compared to their normal peers. 15.3% of HIV girls were short-statured and underweight. None of the study participants were found to be overweight or obese. 40.7% of HIV girls had attained menarche (mean age: 12.58 ± 1.349 years). The appearance of pubic (13.45 ± 1.64 years) and axillary hair (13.73 ± 1.41 years) occurred around 1 year later. The delayed physical growth and puberty attainment of HIV girls than their normal counterparts may be due to the influence of the disease.

Childhood Overweight and Obesity and Pubertal Onset Among Mexican-American Boys and Girls in the CHAMACOS Longitudinal Study.

Secular trends in earlier initiation of puberty have been observed in recent decades. One risk factor appears to be increases in adiposity, as measured by body mass index. This trend is particularly notable among Latino populations, who have higher rates of overweight/obesity compared with non-Latino White youth. Previous research has focused primarily on White girls, resulting in data gaps regarding male puberty and among potentially high-risk populations. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, we examined body mass index at age 5 years (2005-2006) and multiple markers of pubertal onset, assessed repeatedly and longitudinally at 7 in-person visits, starting at age 9 and continuing through age 14 (2009-2015), among 336 Mexican Americans in Salinas, California. We observed no associations among boys, but found significantly earlier thelarche in overweight (HR = 1.7, 95% CI: 1.1, 2.7) and obese girls (HR = 1.5, 95% CI: 1.0, 2.4), menarche in overweight girls (HR = 1.6; CI: 1.0, 2.4), and pubarche in obese girls (HR = 1.9; CI: 1.2, 3.0), compared with normal-weight girls. This study examined an understudied population and included key covariates, such as birth weight and early adverse events, which are typically omitted in studies.

Cohort-based analysis of maternal age at menarche in relation to young adult offspring anthropometric and metabolic parameters.

OBJECTIVES: Age of menarche is a determinant factor of cardiometabolic risk, adiposity and stature at adulthood. However, little is known about the transgenerational effects of age of menarche, especially beyond childhood of any offspring, and the studies remain limited to anthropometric outcomes in children at birth or before adolescence. In the present study, we aim to investigate the relationship of maternal age at menarche (MAM) with anthropometric and metabolic parameters in the young adult offspring (aged 15-35 years) in a Persian population. DESIGN, PATIENTS AND MEASUREMENTS: In this cohort-based cross-sectional study, we recruited 1139 mother-young adult dyads enroled in Rafsanjan Cohort Study (RCS) at adult RCS (aged 35-70 years) and youth RCS (aged 15-35 years) as part of the comprehensive PERSIAN (Prospective Epidemiological Research Studies in IrAN). In this study, MAM was categorized to early (MAM < 12 years), normal (12 ≤ MAM ≤ 14) and late menarche (MAM > 14 years). For these analyses, bivariate and multiple logistic regression models were used to investigate the relationships between late or early MAM and offspring anthropometric and metabolic parameters. RESULTS: Early MAM displayed a significant association with an increased odds ratio (OR) of tall stature adjusting for sex, age, socioeconomic status index, maternal age at birth and maternal height (as genetically determined factor). Sensitivity analysis by sex indicated this relationship to be specific to male offspring only (adjusted OR: 1.84 95% CI: 1.13-3.00, p value: .014). In addition, late MAM displayed a significant association with reduced OR of overweight/obesity and abdominal obesity in daughters only (obesity adjusted OR: 0.49, 95% CI: 0.27-0.88, p value: .018, abdominal obesity adjusted OR: 0.44, 95% CI: 0.23-0.82, p value: .010). dose-response analysis by categorization of MAM, further supported our results. On the contrary, our analyses do not support a significant relationship between MAM and youth metabolic indices, that is, metabolic syndrome, fasting blood sugar (FBS), high-density lipoprotein (HDL) and triglyceride (TG). CONCLUSIONS: The results of the present study indicate an association of maternal age of menarche with anthropometric measures of offspring in young adulthood in a sex differential manner. The data does not support a significant relationship between the metabolic indices FBS, TG and HDL in offspring with MAM. Overall, this study provides evidence for the intergenerational effects of age at menarche in the development of anthropometric measures in offspring in young adulthood (15-35), which is the first study of this kind in this age range.

Prepubertal Internalizing Symptoms and Timing of Puberty Onset in Girls.

Stressful environments have been associated with earlier menarche. We hypothesized that anxiety, and possibly other internalizing symptoms, are also associated with earlier puberty in girls. The Lessons in Epidemiology and Genetics of Adult Cancer From Youth (LEGACY) Girls Study (2011-2016) included 1,040 girls aged 6-13 years at recruitment whose growth and development were assessed every 6 months. Prepubertal maternal reports of daughter's internalizing symptoms were available for breast onset (n = 447), pubic hair onset (n = 456), and menarche (n = 681). Using Cox proportional hazard regression, we estimated prospective hazard ratios and 95% confidence intervals for the relationship between 1 standard deviation of the percentiles of prepubertal anxiety, depression, and somatization symptoms and the timing of each pubertal outcome. Multivariable models included age, race/ethnicity, study center, maternal education, body mass index percentile, and family history of breast cancer. Additional models included maternal self-reported anxiety. A 1-standard deviation increase in maternally reported anxiety in girls at baseline was associated with earlier subsequent onset of breast (hazard ratio (HR) = 1.22, 95% confidence interval (CI): 1.09, 1.36) and pubic hair (HR = 1.15, 95% CI: 1.01, 1.30) development, but not menarche (HR = 0.94, 95% CI: 0.83, 1.07). The association of anxiety with earlier breast development persisted after adjustment for maternal anxiety. Increased anxiety in young girls may indicate risk for earlier pubertal onset.

Delayed age at menarche in chronic respiratory diseases.

OBJECTIVE: Age at menarche (AAM) is an important indicator of physiological development in women, and delayed AAM has been associated with chronic illnesses. We investigated predictive factors at diagnosis that influence AAM in adolescents with chronic respiratory diseases. STUDY DESIGN: AAM was assessed in 1207 northern Italian female aged 11-24 (1062 healthy, 98 with asthma and 47 with cystic fibrosis [CF]). AAM was defined by recall and status quo methods. We studied anthropometric data, metabolic status, diagnosis parameters, presence of irregular menses. Clinical data of subjects with chronic respiratory illness were compared with that of healthy adolescents. RESULTS: Mean AAM for healthy adolescents was 12.49 ± 1.2 years. Mother's AAM was positively associated with that of their daughters (P < .001). BMI was negatively correlated with AAM (P < .001). 69% of healthy adolescents referred regular menses. AAM in the different groups was 12.79 ± 3.0 years for patients with asthma (P < .05 vs healthy) and 13.24 ± 1.44 years for adolescents with CF (P < .0001 vs healthy). In the asthmatic group, 57% of the patients referred regular menses, and no significant differences were found between AAM and control of the disease (ACT test). In the CF group, no correlation was found between the type of CFTR mutation or FEV1% and AAM. 53% of the patients with CF referred regular menses. CONCLUSIONS: AAM in patients with CF and asthma was significantly higher than in healthy adolescents, and menses abnormalities were observed in the last two groups. Inflammation influences the reproductive function in chronic respiratory disease.

Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies.

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.