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)

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.

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.

Aspectos clínicoepidemiológicos de pacientes con cáncer de mama del Policlínico 28 de septiembre / Clinical-Epidemiological Aspects of Patients with Breast Cancer and from the Policlínico 28 de Septiembre of Santiago de Cuba

Introducción: El cáncer de mama es considerado como un serio problema de salud pública por la alta prevalencia tanto en países desarrollados como en desarrollo. Son escasos los estudios clínico-epidemiológicos actualizados en el área de salud del Policlínico 28 de septiembre relacionados con dicha entidad clínica. Objetivo: Caracterizar desde el punto de vista clínico y epidemiológico a pacientes con cáncer de mama del área de salud perteneciente al Policlínico 28 de septiembre. Métodos: Estudio descriptivo en una serie de 35 mujeres mayores de 30 años con diagnóstico confirmado de cáncer de mama. Las variables estudiadas comprendieron edad, antecedentes familiares de cáncer de mama, factores de riesgo generales y hormonales, signos y síntomas clínicos, resultados de estudio ecográfico y diagnóstico histopatológico. Se utilizó el porcentaje como medida de resumen. Resultados: El 42,8 por ciento de la muestra objeto de estudio estuvo comprendido en el grupo de edad de 40-49 años. El 65,7 por ciento del total de mujeres tenía antecedentes familiares de cáncer de mama. La menarquía precoz (54,2 por ciento) y la nuliparidad (48,5 por ciento) representaron los factores de riesgo de mayor incidencia. El 57,1 por ciento de las lesiones diagnosticadas correspondieron a carcinomas en estadío I y IIa. Conclusiones: El cáncer de mama constituye un serio problema de salud en mujeres mayores de 30 años pertenecientes al Policlínico 28 de septiembre del municipio Santiago de Cuba(AU)

Introduction: Breast cancer is considered a serious public health concern due to its high prevalence in both developed and developing countries. There are few updated clinical-epidemiological studies carried out in the health area of the Policlínico Docente 28 de Septiembre related to this clinical entity. Objective: To characterize, from the clinical and epidemiological point of view, the patients with breast cancer and from the health area belonging to the Policlínico Docente 28 de Septiembre. Methods: A descriptive study was carried out with a series of 35 women aged more than 30 years and with a confirmed diagnosis of breast cancer. The variables studied included age, family history of breast cancer, general and hormonal risk factors, clinical signs and symptoms, ultrasound findings and histopathological diagnosis. Percentage was used as summary measure. Results: 42.8 percent of the study sample was in the age group 40-49 years old. Of the total number of women, 65.7 percent had a family history of breast cancer. Early menarche (54.2 percent) and nulliparity (48.5 percent) represented the risk factors with the highest incidence. 57.1 percent of the diagnosed lesions corresponded to stage I and IIA carcinomas. Conclusions: Breast cancer is a serious health problem in women older than 30 years and belonging to the Policlínico Docente 28 de Septiembre, of Santiago de Cuba Municipality(AU)

Association Between Markers of Adiposity During Childhood and Puberty Onset in Latino Girls.

CONTEXT: Prepubertal adiposity is associated with earlier puberty. It is unclear when this association starts, if all adiposity markers are similarly associated, and whether all pubertal milestones are similarly affected. OBJECTIVE: To evaluate the association between different adiposity markers during childhood and the timing of different pubertal milestones in Latino girls. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal follow-up of 539 female participants of the Chilean Growth and Obesity Cohort recruited from childcare centers (mean age 3.5 years) from the southeast area of Santiago, Chile. Participants were singletons born between 2002 and 2003 within the normal birthweight range. Since 2006, a trained dietitian measured weight, height, waist circumference (WC) and skinfolds to estimate body mass index (BMI) Centers for Disease Control and Prevention percentiles, central obesity, percentage of fat mass (%FM), and fat mass index (FMI, fat mass/height2). MAIN OUTCOME: Since 2009, sexual maturation was assessed every 6 months to assess age at (1) thelarche, (2) pubarche, (3) menarche, and (4) peak height velocity (PHV). RESULTS: At thelarche, 12.5% were obese and 2% had central obesity. The median age of pubarche, menarche, and PHV were all associated with markers of adiposity at different time points during childhood whereas thelarche only with %FM and FMI. Adiposity clusters models showed that children with trajectories of high WC, %FM, and FMI during childhood were related with earlier thelarche, pubarche, menarche, and PHV but BMI trajectories only with menarche and PHV. CONCLUSIONS: Higher WC, %FM, and FMI were associated with earlier age at thelarche, pubarche, menarche, and PHV. The effect of BMI was less consistent.

Menstrual Dysfunction in Adolescents with Chronic Illness: A Systematic Review.

STUDY OBJECTIVE: Menstrual dysfunction can impact both the physical and emotional health of young people.1 Multiple chronic diseases have been associated with menstrual dysfunction in adults2; however, there is little research in adolescents, despite nonadherence and suboptimal illness control in this group. We aimed to identify the impact of chronic illness on the age of menarche and the menstrual cycle in adolescents. METHODS: Studies were extracted of female adolescents aged 10-19 who had a chronic physical illness. Data included outcomes on age of menarche and/or menstrual cycle quality. Exclusion criteria aimed to exclude diseases where menstrual dysfunction was a known part of the disease pathophysiology (ie, polycystic ovarian syndrome)3 or in which medications were used that directly impacted gonadal function.4 A literature search (to January 2022) was performed on the EMBASE, PubMed, and Cochrane library databases. Two widely used modified quality analysis tools were used. RESULTS: Our initial search netted 1451 articles, of which 95 full texts were examined and 43 met the inclusion criteria. Twenty-seven papers focused on type 1 diabetes (T1D), with 8 papers examining adolescents with cystic fibrosis and the remaining studying inflammatory bowel disease, juvenile idiopathic arthritis, coeliac disease, and chronic renal disease. Metanalysis of 933 patients with T1D vs 5244 controls demonstrated a significantly later age of menarche in T1D (by 0.42 years; P ≤ .00001). There was also a significant association between higher HbA1c and insulin dose (IU/kg) and later age of menarche. Eighteen papers reviewed other aspects of menstruation, including dysmenorrhea, oligomenorrhoea, amenorrhea, and ovulatory function, with variable findings. CONCLUSION: Most studies were small and in single populations. Despite this, there was evidence of delayed menarche and some evidence of irregular menses in those with cystic fibrosis and T1D. Further structured studies are needed to evaluate menstrual dysfunction in adolescents and how it relates to their chronic illness.

The Accuracy of Early Reproductive History and Physical Activity Participation Recall Across Multiple Age Ranges.

Background: The ability to accurately recall specific reproductive health events is an integral aspect of medical decision making and evaluating a female's overall health and wellness across their lifespan. The Health and Reproductive Survey (HeRS) was developed to recall reproductive events and environmental influences on reproductive characteristics throughout the lifespan of a female. This study aimed to determine how reliably women recall certain events during menarche and early reproductive years. It was hypothesized that age at menarche, hormonal contraceptive use, and physical activity would be recalled reliably among all age ranges, while the recall reliability for cycle regularity and length would be more inconsistent with advancing age. Materials and Methods: A total of 144 participants (age: 32.73 ± 11.92), completed the HeRS on two occasions spaced 4 months apart to investigate recall reliability. Cohen's kappa coefficient was used to assess the consistency of categorical responses and 95% limits of agreement were used for continuous data. Results: Although physical activity changes had greater variability than anticipated (0.79), the recall reliability among the youngest (1) and oldest (0.89) age groups was high, and females were able to consistently recall the age of menarche (0.83), physical activity level (0.9), cessation of period during early reproductive years (0.91), and birth control use following menarche (0.85) and during the early reproductive years (0.9). Conclusions: The HeRS is a useful tool for reliably recalling reproductive history and physical activity participation across multiple age ranges and can be utilized to gather crucial information throughout the reproductive lifespan.

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.

Relationship between age at menarche and metabolic diseases in Korean postmenopausal women: The Korea National Health and Nutrition Examination Survey 2016-2018.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Early menarche may be associated with an increased risk of metabolic diseases such as diabetes and cardiovascular disease. This study aimed to investigate the effect of menarche age and the risk of diabetes and metabolic syndrome in Korean postmenopausal women. METHODS: We analyzed 4,933 postmenopausal women (mean age: 64.7 years) using the Korean National Health and Nutritional Examination Survey 2016-2018. Subjects were divided into three groups according to menarche age (early menarche: ≤ 12 years (n = 451), reference: 13-16 years (n = 3,421), and late menarche: ≥ 17 years (n = 1,061)). Logistic regression analysis was used to estimate the odds ratio (OR) for diabetes and metabolic syndrome. RESULTS: Women with an early menarche age were younger, more educated, and had higher income than the other groups (p-value < 0.001). There were no differences in body mass index, blood pressure, fasting glucose, HbA1c, and cholesterol levels among the three groups. After adjusting for potential confounding factors, early menarche age was significantly associated with the risk of diabetes (OR 1.435, 95% confidence interval (CI): 1.069-1.928). The prevalence of metabolic syndrome in all subjects was 41.1%. After adjusting for potential confounding factors, the OR of metabolic syndrome in the early menarche group was 1.213 (95% CI: 0.971-1.515). CONCLUSION: The risk of diabetes was 1.43 times higher in postmenopausal Korean women with early menarche. Although the risk of metabolic syndrome was not statistically significant, it showed a tendency to increase in the early menarche group. Our results suggest that age at menarche may be helpful in diabetes risk stratification and early interventions for postmenopausal women.

Early physical maturation and subjective health complaints in adolescent girls: a pooled cross-sectional analysis.

BACKGROUND: Although adolescents are generally healthy, subjective health complaints (SHC) are common in this age group, especially in adolescent girls. We explored the association between early menarche and the frequency of psychosomatic symptoms and how this association varies between countries. METHODS: Our sample included 298 000 adolescent girls from 2002, 2006, 2010 and 2014 cycles of the Health Behaviour in School-aged Children (HBSC) study in 41 European and North American countries. School surveys measured the frequency of eight psychosomatic symptoms in the past 6 months. Early maturation was defined as self-reported age at menarche below 11 years. Using logistic regression, we estimated adjusted ORs (aORs) and 95% CIsof experiencing each psychosomatic symptom at least more than once a week and experiencing two or more symptoms at least more than once a week. RESULTS: Early menarche occurred in 4.73% of the sample and was positively related to headache, stomachache, backache, feeling low, irritability or bad temper, feeling nervous, difficulties in sleeping, feeling dizzy and two or more of these symptoms, respectively (all p values<0.001). The interactions between early menarche and survey circle were non-significant. Changing the age criterion to 12 years did not affect the results. The associations between early menarche and psychosomatic symptoms were robust across the HBSC-participating counties with two age criteria. CONCLUSIONS: Early menarche positively relates to various psychosomatic symptoms in European and North American adolescent girls. Our findings suggest that early-maturing girls may need early supportive interventions.

Dietary Fat and Polyunsaturated Fatty Acid Intakes during Childhood Are Prospectively Associated with Puberty Timing Independent of Dietary Protein.

Dietary fat and fat quality have been inconsistently associated with puberty timing. The aim of this study was to investigate the prospective associations of dietary fat, saturated fatty acid (SFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) with puberty timing. Using longitudinal data from China Health and Nutrition Survey (CHNS) and Southwest China Childhood Nutrition and Growth (SCCNG) Study, we analyzed dietary data, anthropometric measurements, and potential confounders. Dietary intakes were assessed by 3-day 24-h recalls. Age at Tanner stage 2 for breast/genital development (B2/G2) and age at menarche/voice break (M/VB) were used as puberty development markers. Cox proportional hazard regression models were used to estimate the relevance of dietary intake of total fat, SFA, PUFA, and MUFA on puberty timing. Among 3425 girls and 2495 boys, children with higher intakes of total fat and PUFA were more likely to reach their B2/G2 or M/VB at an earlier age. Associations were not attenuated on additional adjustment for childhood dietary protein intake. However, higher intakes of SFA or MUFA were not independently associated with puberty development. A higher intake of dietary fat and PUFA in prepuberty was associated with earlier puberty timing, which was independent of dietary protein intake.

Early menarche in visually impaired girls: evidence and hypothesis of light-dark cycle disruption and blindness effect on puberty onset.

Puberty onset is tightly regulated by a broad spectrum of neuroendocrine signals and peripheral stimuli which coordinate the hypothalamic-pituitary-gonadal (HPG) axis activation. Numerous studies suggest that light stimulation influences HPG axis function; however, the effect of blindness on puberty timing remains controversial. Given that menarche is a suitable marker for sexual development initiation, the evaluation of the age at which blind girls attain it allows to indirectly assess the effect of light-dark cycle disruption on pubertal development. The present investigation aimed to review the evidence regarding menarcheal age drift in visually impaired girls, as well as to discuss the findings based on the existing hypotheses of the physiological mechanisms linking the light-dark cycle and photic sensitivity loss to the onset of puberty. Eleven studies were retrieved from a literature search conducted in PubMed, Scopus, ScienceDirect, SpringerLink, and Google Scholar databases. Eight studies concluded that light perception impairment is related to a moderately earlier age at menarche. Moreover, the evidence gathered in this review suggests a positive association between the degree of light perception loss and precocious menarcheal onset; yet, no conclusive outcomes were found regarding menarche advancement in acquired versus congenital blindness. We encourage further research aiming to elucidate the physiological mechanism underlying photosensitive regulation and blindness effect on the neuroendocrine pathways involved in human sexual maturation.

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.

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.

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.

A Longitudinal Study of Bone Mineral Accrual during Growth in Competitive Premenarcheal Rhythmic Gymnasts.

The purpose of this investigation was to study whether prolonged competitive rhythmic gymnastics training influenced bone mineral accrual in premenarcheal girls. Eighty-nine girls (45 rhythmic gymnasts [RG] and 44 untrained controls [UC]) between 7 and 9 years of age were recruited and measured annually for four years (not all participants were measured at every occasion). Dual energy x-ray absorptiometry was used to assess the development of whole body (WB), femoral neck (FN) and lumbar spine (LS) bone mineral content (BMC). In addition, body composition, blood adipokine and jumping performance characteristics were obtained. For longitudinal analyses, hierarchical mixed-effects models were constructed to predict differences in the development of WB, FN and LS BMC between RG and UC groups, while accounting for differences in body composition, blood adipokine and jumping performance values. It appeared that from 8 years of age, RG had lower (p < 0.05) fat mass and leptin values, and higher (p < 0.05) jumping performance measures in comparison with UC girls. Hierarchical mixed-effects models demonstrated that RG had 71.9 ± 12.0, 0.23 ± 0.11 and 1.39 ± 0.42 g more (p < 0.05) WB, FN and LS BMC, respectively, in comparison with UC girls. In addition, WB, FN and LS BMC increased more (p < 0.05) between 7 to 12 years of age in RG girls in comparison with UC. In conclusion, these findings suggest that the prolonged exposure to competitive rhythmic gymnastics trainings in premenarcheal girls is associated with greater bone mineral accrual despite lower body fat mass and leptin values.

[Epidemiology and clinical features of patients with breast cancers hospitalized in the Department of Oncology in Fianarantsoa, Madagascar from 2011 to 2018]. / Aspects épidémio-cliniques des cancers du sein au Service d´Oncologie de Fianarantsoa, Madagascar de 2011 à 2018.

INTRODUCTION: we conducted the first epidemiological study of patients with breast cancers living in Fianarantsoa. The purpose of this study was to describe the epidemiology and clinical features of these patients in the Department of Oncology Fianarantsoa. METHODS: we conducted a retrospective and descriptive study in the Department of Oncology at the University Hospital Center of Tambohobe over a period of 8 years (2011-2018). All patients with breast cancer diagnosed based on cytological and/or histological examination were included. The parameters studied were: age, occupation, a family history of breast cancer, menarche, menopause, parity, use of oral contraceptives, smoking, circumstances leading to detection, breast symptoms, signs of locoregional and distant spread, tumour site and stage of the disease. RESULTS: the study included 62 patients with an average age of 52.83 ± 10.47 years. Housewives accounted for 39% (n = 24) of cases. No patient had an early menarche. Late menopause had occurred in 6.45% (n = 4) of patients and a family history of breast cancer was found in 8.06% (n = 5) of patients. Chewing tobacco was used by 17.74% (n = 11) of patients. Patients reporting breast symptoms accounted for 95.2% (n = 59). Breast cancers had affected the upper outer quadrant in 53.23% (n = 33) of cases. Stage III breast cancer was diagnosed in 55% (n = 34) of cases and stage IV in 32% (n = 20) of cases. CONCLUSION: in patients diagnosed with cancer at an advanced stage, risk factors for breast cancer were little observed.

Joint Associations of Actual Age and Genetically Determined Age at Menarche With Risk of Mortality.

Importance: Previous studies have shown an association between actual age at menarche and risk of all-cause mortality; however, the results are inconsistent, and no study has analyzed the joint associations between genetic susceptibility and actual age at menarche with the risk of mortality in prospective cohorts. Objectives: To investigate joint associations of actual age and genetically determined age at menarche with risk of all-cause mortality. Design, Setting, and Participants: This prospective cohort study was conducted using data from the UK Biobank population across the United Kingdom from March 13, 2006, to October 1, 2010. A total of 264 546 women aged between 39 and 71 years with actual menarcheal age were included in this study; 246 676 of these women had genetic data available. Actual age at menarche was obtained from the touchscreen questionnaire at recruitment from 2006 to 2010. Genetically determined age at menarche was assessed by a genetic risk score. Statistical analysis was performed from August 22 to December 12, 2019. Exposure: Age at menarche. Main Outcomes and Measures: A multivariable Cox proportional hazards regression model was used to assess associations of actual or genetically determined age at menarche with risk of all-cause mortality. Results: The mean (SD) age of the study population at baseline was 56.4 (8.0) years, and the mean (SD) age at menarche included in the analyses was 13.0 (1.6) years. During a median of 9.0 years (range, 8.3-9.7 years) of follow-up, 7761 deaths were documented among the women with actual age at menarche, and 7054 deaths were documented among the women with genetically determined age at menarche. Both the actual age at menarche and the genetically determined age at menarche showed a U-shaped association with the risk of all-cause mortality (lowest actual age [<12 years] vs reference age [15 years]: hazard ratio [HR], 1.16 [95% CI, 1.07-1.26]; highest actual age [≥16 years] vs reference age [15 years]: HR, 1.17 [95% CI, 1.05-1.31]; P < .001 for quadratic trend; genetic risk score [GRS] of 1 vs reference score [GRS of 4]: HR, 1.10 [95% CI, 1.01-1.19; GRS of 6 vs reference score [GRS of 4]: HR, 1.09 [95% CI, 1.00-1.18]; P = .03 for quadratic trend). Significant interactions were also found between actual age at menarche and genetically determined age at menarche with all-cause mortality (HR of mortality associated with age of menarche <12 year was 1.24 [95% CI, 1.10-1.40] in the GRS of 1 group and 1.44 [95% CI, 1.21-1.72] in the GRS of 6 group; P = .001 for interaction). Women with mismatch of actual age and genetically determined age at menarche had the highest mortality risks; participants with the lowest genetic risk score and the highest age at menarche had an HR of 2.12 (95% CI, 1.58-2.83), and participants with the highest GRS and the lowest age at menarche had an HR of 1.44 (95% CI, 1.21-1.72). Conclusions and Relevance: The results suggest that both actual age and genetically determined age at menarche exhibit U-shaped associations with all-cause mortality. Women with mismatch of actual age and genetically determined age at menarche may have the highest risk of all-cause mortality.

Faster life history strategy manifests itself by lower age at menarche, higher sexual desire, and earlier reproduction in people with worse health.

Factors which indicate lower life expectancy also induce switching to a faster life strategy, that is, a higher investment in current reproduction at the expense of future reproduction and body maintenance. We tested a hypothesis according to which impairment of individual health serves as a signal for switching to a faster life strategy using online-gathered data from 32,911 subjects. Worse health was associated with lower age at menarche and earlier initiation of sexual life in women and higher sexual desire and earlier reproduction in both sexes. Individuals with worse health also exhibited lower sexual activity, lower number of sexual partners, and lower total number of children. These results suggest that impaired health shifts individuals towards a faster life strategy but also has a negative (physiological) effect on behaviours related to sexual life. Signs of a faster life strategy were also found in Rh-negative men in good health, indicating that even just genetic predisposition to worse health could serve as a signal for switching to a faster life strategy. We suggest that improved public health in developed countries and the resulting shift to a slower life strategy could be the ultimate cause of the phenomenon of demographic transition.

Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts.

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis. SIGNIFICANCE: Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.