Timing Of Menarche Research Articles

Identifying environmental exposure profiles associated with timing of menarche: A two-step machine learning approach to examine multiple environmental exposures

BackgroundVariation in the timing of menarche has been linked with adverse health outcomes in later life. There is evidence that exposure to hormonally active agents (or endocrine disrupting chemicals; EDCs) during childhood may play a role in accelerating or delaying menarche. The goal of this study was to generate hypotheses on the relationship between exposure to multiple EDCs and timing of menarche by applying a two-stage machine learning approach. MethodsWe used data from the National Health and Nutrition Examination Survey (NHANES) for years 2005–2008. Data were analyzed for 229 female participants 12–16 years of age who had blood and urine biomarker measures of 41 environmental exposures, all with >70% above limit of detection, in seven classes of chemicals. We modeled risk for earlier menarche (<12 years of age vs older) with exposure biomarkers. We applied a two-stage approach consisting of a random forest (RF) to identify important exposure combinations associated with timing of menarche followed by multivariable modified Poisson regression to quantify associations between exposure profiles (“combinations”) and timing of menarche. ResultsRF identified urinary concentrations of monoethylhexyl phthalate (MEHP) as the most important feature in partitioning girls into homogenous subgroups followed by bisphenol A (BPA) and 2,4-dichlorophenol (2,4-DCP). In this first stage, we identified 11 distinct exposure biomarker profiles, containing five different classes of EDCs associated with earlier menarche. MEHP appeared in all 11 exposure biomarker profiles and phenols appeared in five. Using these profiles in the second-stage of analysis, we found a relationship between lower MEHP and earlier menarche (MEHP ≤ 2.36 ng/mL vs >2.36 ng/mL: adjusted PR = 1.36, 95% CI: 1.02, 1.80). Combinations of lower MEHP with benzophenone-3, 2,4-DCP, and BPA had similar associations with earlier menarche, though slightly weaker in those smaller subgroups. For girls not having lower MEHP, exposure profiles included other biomarkers (BPA, enterodiol, monobenzyl phthalate, triclosan, and 1-hydroxypyrene); these showed largely null associations in the second-stage analysis. Adjustment for covariates did not materially change the estimates or CIs of these models. We observed weak or null effect estimates for some exposure biomarker profiles and relevant profiles consisted of no more than two EDCs, possibly due to small sample sizes in subgroups. ConclusionA two-stage approach incorporating machine learning was able to identify interpretable combinations of biomarkers in relation to timing of menarche; these should be further explored in prospective studies. Machine learning methods can serve as a valuable tool to identify patterns within data and generate hypotheses that can be investigated within future, targeted analyses.

FACTORS AFFECTING THE RECEDING AGE OF ONSET OF MENARCHE IN YOUNG GIRLS – AN OBSERVATIONAL STUDY

Background: The time of first menarche is an important milestone in female sexual maturation. Studies have shown trends of decreasing age of menarche in most Indian states. Objective: To trace the factors associated with receding age at menarche and to evaluate the strength of association between those factors with receding age at menarche. Materials and methods: An observational study was done in the schools in Davangere from July 2018 to June 2019. 372 menstruating girls between the age of 9–15 years were included in the study. The participants data regarding chronological age, age of menarche, socioeconomic status, physical activity and diet were collected using a questionnaire. The anthropometric measurements were taken using standard techniques and general physical examination was done for all the participants. Results: The mean age of attainment of menarche was 11.94 ± 1.02 years. The study had a strong association between age at menarche and socioeconomic status (p&lt;0.001). Body mass index (BMI) and waist circumference (WC) was inversely and significantly associated with age of menarche (p&lt;0.01). Conclusion: The world wide trends of declining age of menarche were seen in our study too. The factors affecting being mother’s age of menarche, BMI, Waist circumference and higher socioeconomic status. This underline that further evaluation of factors associated with it and studying future implications of lower age at menarche is important.

Association between age at menarche and body mass index, waist circumference, waist to hip ratio, and waist to height ratio in adult women.

The aim of the present study was to examine associations between age at menarche and body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) in young adult women. Anthropometric data and age at menarche information were collected in two cross-sectional surveys conducted in the years 2004-2006 (Cohort 1) and 2016-2018 (Cohort 2). A total of 2419 women, aged 19-24 years., were included. Statistically significant relationships between age at menarche and BMI, WHtR, and WC were observed. The values of the anthropometric parameters decreased with increasing age at menarche. The onset of menstruation before the age of 12 years. was linked to a heightened risk of overweight and obesity (BMI ≥ 25) and abdominal obesity defined as WC > 80 cm and/or WHtR ≥ 0.5. First menstruation after the age of 14 y. was associated with a lower risk of overweight and obesity (BMI ≥ 25, WC > 80 cm and/or WHtR ≥ 0.5), as well as a higher risk of being underweight (BMI < 18.5 and/or WHtR < 0.4). Associations between anthropometry and menarcheal timing were stronger in Cohort 1. Both early and late onset of menarche are associated with abnormal body composition: Early menarche is associated with overweight, while later maturing girls have a heightened risk of underweight.

Association between factors related to the pregnancy, neonatal period, and later complications (especially asthma) and menarcheal age in a sample of Lebanese girls

BackgroundStudies about the majority of the factors that may potentially influence the pubertal timing and menarche were controversial. The objective was to evaluate the association between factors related to the pregnancy, neonatal period, and the complications that may happen later in life and the menarcheal age in a sample of Lebanese girls admitted or not to the NICU at birth. Our secondary objective was to try to find, for the first time in literature, a correlation between respiratory distress at birth and the need of oxygen therapy with the age of the first menses in these girls.MethodsIt is a cross-sectional retrospective study, conducted between January and March 2019. Our sample included all the 2474 girls born in Notre-Dame-de-Secours hospital, between 2000 and 2005; the sample consisted of 297 girls (97 girls admitted to the NICU and 200 randomly chosen to participate in our study with a ratio of 1:2 (1 girl admitted to the NICU vs 2 girls born in the nursery).ResultsAsthma later in life was significantly associated with lower age at menarche in girls, whereas a higher mother’s age at menarche and a higher gestational age were significantly associated with higher age at menarche in girls. When taking each cause of NICU admission as an independent variable, showed that a higher mother’s age at menarche was significantly associated with higher age at menarche in girls, whereas a higher number of days of phototherapy, a preeclampsia in the mother during pregnancy and asthma later in life in the girl were significantly associated with a lower age at menarche in girls.ConclusionThe timing of menarche seems to be associated with many factors in Lebanese girls that should not be disregarded by physicians.

Pubertal timing in boys and girls born to mothers with gestational diabetes mellitus: a systematic review.

ContextThe incidence of gestational diabetes mellitus (GDM) has been on the rise, driven by maternal obesity. In parallel, pubertal tempo has increased in the general population, driven by childhood obesity.ObjectiveTo evaluate the available evidence on pubertal timing of boys and girls born to mothers with GDM.Data sourcesWe searched MEDLINE, EMBASE, CINAHL Plus, Cochrane library and grey literature for observational studies up to October 2019.Study selection and extractionTwo reviewers independently selected studies, collected data and appraised the studies for risk of bias. Results were tabulated and narratively described as reported in the primary studies.ResultsSeven articles (six for girls and four for boys) were included. Study quality score was mostly moderate (ranging from 4 to 10 out of 11). In girls born to mothers with GDM, estimates suggest earlier timing of pubarche, thelarche and menarche although for each of these outcomes only one study each showed a statistically significant association. In boys, there was some association between maternal GDM and earlier pubarche, but inconsistency in the direction of shift of age at onset of genital and testicular development and first ejaculation. Only a single study analysed growth patterns in children of mothers with GDM, describing a 3-month advancement in the age of attainment of peak height velocity and a slight increase in pubertal tempo.ConclusionsPubertal timing may be influenced by the presence of maternal GDM, though current evidence is sparse and of limited quality. Prospective cohort studies should be conducted, ideally coupled with objective biochemical tests.

Association Between Reproductive Life Span and Incident Nonfatal Cardiovascular Disease

Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD. To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause. Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019. Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older. First nonfatal CVD event, including coronary heart disease and stroke events. A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (<30 years) were at 1.71 (95% CI, 1.58-1.84) times higher risk of incident CVD events than women with a reproductive life span of 36 to 38 years after adjustment for covariates. This association remained unchanged when adjusted for age at menarche but was attenuated to 1.26 (95% CI, 1.09-1.46) when adjusted for age at menopause. There was a significant interaction between reproductive life span and age at menarche associated with CVD risk (P < .001). Women who had both short reproductive life span (<33 years) and early menarche (age ≤11 years) had the highest risk of CVD (hazard ratio, 2.06; 95% CI, 1.76-2.41) compared with those with a reproductive life span of 36 to 38 years and menarche at age 13 years. Short reproductive life span was associated with an increased risk of nonfatal CVD events in midlife, and the risk was significantly higher for women with early age at menarche.

Modern dietary pattern is prospectively associated with earlier age at menarche: data from the CHNS 1997\u20132015

BackgroundEarly age at menarche is associated with risk of several chronic diseases. Prospective study on the association between dietary pattern and timing of menarche is sparse. We examined whether dietary patterns prior to the menarche onset were prospectively associated with menarcheal age in Chinese girls.MethodsOne thousand one hundred eighteen girls aged 6–13 y in the China Health and Nutrition Survey (CHNS) with three-day 24-h recalls and information on potential confounders at baseline were included in the study. Dietary patterns were identified using principal component analysis. Age at menarche was self-reported at each survey. Cox proportional hazard regression models were performed to examine the associations of premenarcheal dietary patterns and menarcheal timing. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.ResultsThree major dietary patterns were identified: modern dietary pattern, animal food pattern, and snack food pattern. After adjustment for age at baseline, region, ethnicity, maternal education level, energy intake at baseline, and body mass index Z-score at baseline, girls in the highest quartile of modern dietary pattern score had a 33% higher probability of experiencing menarche at an earlier age than those in the lowest quartile (HR: 1.33, 95% CI: 1.002–1.77, p for trend = 0.03). No significant association was found for the animal food pattern or snack food pattern.ConclusionsHigher adherence to modern dietary pattern during childhood is associated with an earlier menarcheal age. This association was independent of premenarcheal body size.

Heritability of pubertal timing: detailed evaluation of specific milestones in healthy boys and girls.

Pubertal timing is highly heritable. Observational studies were inconclusive concerning a potential sex-specific difference in the parental contribution, while genome-wide association studies highlighted a heterogeneity in the genetic architecture of pubertal timing between sexes. Our objectives were to evaluate the association of timing of pubertal milestones in offspring with parental pubertal timing and to identify the genetic basis of the heterogeneity. (1.) Population-based mixed cross-sectional/longitudinal cohort (2006-2014, COPENHAGEN Puberty Study) comprising 1381 healthy Danish children including their parents. (2.) UK Biobank-based summary statistics of genetic data on timing of menarche (n = 188 644), voice-break (n = 154 459) and facial hair (n = 161 470). (1.) Participants underwent clinical examination(s) including blood sampling. Parental pubertal timing was obtained by questionnaire. Timing of milestones were analyzed using SAS-lifereg. (2.) Genetic correlations between pubertal outcomes were estimated using LD Score regression. Genetic heterogeneity was analyzed using METAL. We observed significant associations of relative parental pubertal timing with timing of pubertal milestones in offspring of concordant sex, that is, fathers/sons (e.g. testicular enlargement: P = 0.004, β = 0.34 years per relative category) and mothers/daughters (e.g. thelarche: P < 0.001, β = 0.45 years per relative category). Fewer milestones were associated with relative parental pubertal timing in offspring of discordant sex compared to concordant sex. Large-scale genetic data highlight both moderate to strong genetic correlations between timing of menarche, voice-break and facial hair. Out of 434 lead single-nucleotide polymorphisms significantly associated with at least one outcome, 39 exhibited a significant genetic heterogeneity between sexes (P < 1.15 × 10-4). Our results highlight a distinct genetic heterogeneity of pubertal timing between sexes.

1631-P: Age at Menarche and Its Association with the Metabolic Syndrome in Type 1 Diabetes

Early menarche has been associated with a higher risk of metabolic syndrome (MetS), CVD and its risk factors in the general population. However, limited data exists regarding the association between age at menarche and MetS in women with type 1 diabetes (T1D), a population in which menarche may be delayed. We thus assessed the ability of age at menarche to predict incident MetS in female participants (n=235) of the EDC study, a cohort of childhood onset T1D. MetS was defined using modified AHA NCEP ATP III criteria: waist circumference ≥ 89 cm; triglycerides ≥ 150 mg/dL or treatment for elevated triglycerides; HDL cholesterol &amp;lt; 50 mg/dL; systolic/diastolic blood pressure ≥130/85 mmHg or on antihypertensive medications. Since all participants met the criteria of hyperglycemia, any two of the remaining four criteria were required for diagnosis of MetS. Participants were divided into 3 menarche timing groups: early (≤11 years, n=22), normal (12∼14 years, n=163) and delayed menarche (≥15 years, n=50). At baseline, women with delayed menarche were with longer diabetes duration and more likely to have lower estimated glomerular filtration rate (eGFR) compared with the other groups (all p-values&amp;lt;0.05). However, univariately, the incidence of MetS during the 25-year follow-up did not differ by menarche timing group (63.6% vs. 49.1% vs. 46.0%, respectively, p=0.37). In multivariable Cox models, compared with the normal menarche group, women with early and delayed menarche had non-significantly higher (HR =1.42, p=0.26) and lower (HR =0.89, p=0.64) hazards of developing MetS, respectively. Duration of T1D, HbA1c, BMI and smoking history were significantly associated with a greater risk of MetS, whereas eGFR was significantly associated with a lower hazard of MetS. In conclusion, unlike findings in the general population where early menarche increased the risk of MetS, in this cohort of women with T1D the incidence of MetS did not differ significantly by menarche timing group. Disclosure J. Ju: None. D. Rubinstein: None. S.R. El Khoudary: None. T.J. Orchard: None. T. Costacou: None. Funding National Institutes of Health (DK34818)

Mini review: The FDA-approved prescription drugs that induce ovulation in women with ovulatory problems.

Infertility is defined as not being able to become pregnant after 12 months or more of unprotected sexual intercourse. Female infertility as a serious health issue can result from ovulation disorders, menstrual cycle problems, structural problems, and environmental factors. Ovulation occurs once a month between the time of menarche and menopause. The release of a mature egg from the ovary is controlled with the hypothalamic-pituitary-ovarian axis. Several hormones such as gonadotropin-releasing hormone (GnRH), FSH (follicle-stimulating hormone), LH (luteinizing hormone), estrogen, and progesterone play fundamental roles in the ovulation process. Both FSH and LH are the main treatment for women with ovulation disorders. Depending on the reasons for infertility, several different types of treatment are available for infertile women. Fertility drugs as an important part of treatment work like the natural hormones to treat infertility. Several fertility drugs can regulate ovulation and the release of an egg from the ovary in women with polycystic ovary syndrome (PCOS) or undergoing in vitro fertilization (IVF) treatment. This mini-review is about the FDA-approved prescription drugs that induce ovulation in women with ovulatory problems.

SUN-725 Clinical and Genetic Features of Families with Maternally Inherited Central Precocious Puberty

Context: The clinical recognition of familial central precocious puberty (CPP) has significantly increased in the last years. This fact can be related to the recent descriptions of genetic causes associated with this pediatric condition, such as loss-of-function mutations of two imprinted genes (MKRN3 and DLK1). Inherited defects in both genes cause paternally inherited CPP. However, no genetic abnormality has been described in families with maternally inherited CPP so far. Objectives: To characterize the clinical and genetic features of several families with maternally inherited CPP. Setting and Participants: We analyzed clinical and genetic features of children with familial CPP. No brain MRI alterations were detected in the selected patients with CPP. MKRN3 and DLK1 pathogenic mutations were excluded. Whole-exome sequencing was performed in selected cases. Results: We studied 177 children from 141 families with familial CPP. Paternal inheritance was evidenced in 44 families (31%), whereas 58 (41%) had maternally inheritance. Indeterminate inheritance was detected in the remaining families. Maternally inherited CPP affected mainly female patients (69 girls and two boys). Thelarche occurred at mean age of 6.1 ± 1.9 years in this female group. Most of girls had Tanner 3 (41%) and Tanner 4 (35%) breast development at first evaluation. One boy had additional syndromic features (macrosomia, autism, bilateral eyelid ptosis, high arcade palate, irregular teeth and abnormal gait). The pedigree analysis of patients with maternally inherited CPP revealed the following affected family members: 42 mothers, 10 grandmothers, 11 sisters, 12 aunts, and 11 female cousins. Most of the families (41) had two affected consecutive generations, while eight families had three affected generations. No consanguinity was referred. Ongoing molecular analysis revealed two rare heterozygous variants in the boy with syndromic CPP and three affected family members with precocious menarche (mother, maternally half-sister, and maternally aunt): a frameshift deletion (p.F144fs) in MKKS; and a missense variant (p.P267L) in UGT2B4, which encodes a protein involved in estrogen hydroxylation and it was related to menarche timing in genome-wide association studies. Conclusions: Maternally inherited CPP was diagnosed mainly in girls, who had thelarche at mean age of 6 years old. Dominant pattern of inheritance was more prevalent, with direct maternal transmission in 72% of the studied families. New candidate genes might be implicated with maternally inherited CPP.

SUN-081 High Throughput Genetic Analysis Revealed Novel Genomic Loci and Candidate Genes Involved in Central Precocious Puberty Associated with Complex Phenotypes

Background: Central precocious puberty (CPP) is mostly described as an isolated entity. Few studies have shown an association of CPP with complex cases or genetic syndromes, but without making inferences on molecular causalities.Objective: To genetically investigate a cohort of patients with CPP associated with complex phenotypes using high throughput methodologies.Patients and methods: From a large cohort of patients with idiopathic CPP followed at a university hospital outpatient clinic, thirty-eight patients were selected for high throughput genetic investigation for presenting at least 3 additional clinical features and conditions, characterizing complex phenotypes. All had normal brain MRI. Pathogenic allelic variants in CPP known genes were initially excluded. All patients were submitted to genomic microarray (SNP or CGH arrays). A subset of patients was also submitted to whole-exome sequencing (11 cases) or target panel sequencing (18 cases).Results: Among the group of 38 patients (35 girls, 4 boys; 21 sporadic, 17 familial), mean age at puberty onset was 5.8 ±2.1 and 8.3 ±3.0 yr in girls and boys, respectively. The more prevalent clinical features described included metabolic, growth and neurocognitive phenotypes; less prevalent features included dysmorphic features and congenital anomalies. Pathogenic or probably pathogenic genetic defects were identified in 9 cases: 5 sporadic (all identified as de novo) and 4 familial. Defects in sporadic cases were as follows: three cases with 7q11.23 deletion (Williams syndrome); one girl with ventricular arrhythmia presenting a rare 1p31.3 duplication, involving NFIA gene coding a transcription factor of NFI family with hypothalamic expression; and one girl with imperforate anus and learning difficulties with rare frameshift variants in AREL1 gene (p.Ser229Aspfs*3) coding an ubiquitin ligase, and TNRC6B gene (p.Gly665Leufs*35) coding a regulator of translational inhibition. In the four familial cases, the genetic defects segregated with CPP in a dominant inheritance mode. Three cases from unrelated families presented growth phenotypes and Xp22.33 deletions, including SHOX gene and other elements. One boy with maternal familial CPP and autism had two rare potentially pathogenic variants: a frameshift deletion in MKKS gene (p.Phe144Leufs*14); and a missense variant (p.Pro267Leu) in UGT2B4 gene. Interestingly, the later gene encodes a protein involved in estrogen hydroxylation and is associated to menarche timing in GWAS.Conclusion: Novel genetic defects were identified in 23% cases of CPP associated with complex phenotypes. Three chromosomal regions represented loci potentially implicated in CPP: Xp22.33, 7q11.23 and 1p31.3. Five genes were identified as candidate genes associated with CPP: NFIA, AREL1, TNRC6B, MKKS and UGT2B4.

Timing of Menarche Impacts Hippocampal Connectivity in Youth at Clinical-High Risk for Psychosis

Timing of Menarche Impacts Hippocampal Connectivity in Youth at Clinical-High Risk for Psychosis

Timing of menarche and abnormal hippocampal connectivity in youth at clinical-high risk for psychosis

The “estrogen hypothesis” suggests that estrogen is a protective factor against psychotic disorders such as schizophrenia. Although the precise protective mechanisms are still unclear, one potential explanation lies in the role that increased estrogens play in mediating hippocampal plasticity, as this may reduce hippocampal dysconnectivity that is characteristically observed in psychosis. In support of this view, later age at menarche- less available estrogen during critical early adolescent development- is related to earlier onset of psychosis and increased symptom severity. Furthermore, if estrogens have protective effects, then we should see this effect in the psychosis risk period in those at clinical high-risk (CHR) for psychosis — i.e., individuals showing attenuated symptoms at imminent risk for transitioning to a psychotic diagnosis. This study examined whether earlier age at menarche would result in more normative hippocampal connectivity in CHR youth; menarche is an easily assessed, developmental marker associated with the availability of estrogens. Resting-state connectivity was examined in sixty female participants (26 CHR and 34 healthy control; age 12–21) using a cross-sectional approach; hippocampal connectivity was found to relate to age at menarche. Later age at menarche in the CHR group related to increased hippocampal dysconnectivity to the occipital cortex (a region with a neurotrophic response to estrogen) compared to the controls. Results suggest that earlier availability of estrogens may have neuroprotective effects on hippocampal plasticity. Findings have relevance for understanding sex differences and etiology, as well as guiding novel treatments.

Delayed menarche in girls with chronic kidney disease and the association with short stature.

Children with chronic kidney disease (CKD) have delays in normal growth and pubertal development. We describe factors associated with delayed menarche and the association of delayed menarche with short stature in girls with CKD. Two hundred eighty-seven girls with CKD onset prior to menarche within the Chronic Kidney Disease in Children (CKiD) cohort were studied. Delayed menarche was defined as menarche at age 15years or older; short stature was defined as last available height 2 standard deviations below projected adult height. Kaplan-Meier cumulative incidence function was used to estimate median age at menarche. Chi-squared and Wilcoxon rank-sum tests were used to assess factors associated with delayed menarche. Chi-squared test was used to evaluate the association between delayed menarche and short stature. Among 287 girls, 68 enrolled with prevalent menarche, 131 were observed to have incident menarche, and 88 were pre-menarchal at their last study visit. Median age at menarche was 12years. Ten percent had delayed menarche. African American race, lower estimated glomerular filtration rate, ever corticosteroid use, and longer CKD duration were associated with delayed menarche (p < 0.05). Girls with delayed menarche had lower height and weight percentiles at the time of menarche (p < 0.05). Sixty-one percent of girls with delayed menarche had short stature compared with only 35% of girls without delayed menarche (p = 0.03). Median age at menarche is similar among girls with CKD and healthy girls. Ten percent of girls with CKD had delayed menarche and may be at risk for short stature.

A Systematic Literature Review of Factors Affecting the Timing of Menarche: The Potential for Climate Change to Impact Women's Health.

Menarche is the first occurrence of a woman’s menstruation, an event that symbolizes reproductive capacity and the transition from childhood into womanhood. The global average age for menarche is 12 years and this has been declining in recent years. Many factors that affect the timing menarche in girls could be affected by climate change. A systematic literature review was performed regarding the timing of menarche and four publication databases were interrogated: EMBASE, SCOPUS, PubMed, and Cochrane Reviews. Themes were identified from 112 articles and related to environmental causes of perturbations in menarche (either early or late), disease causes and consequences of perturbations, and social causes and consequences. Research from climatology was incorporated to describe how climate change events, including increased hurricanes, avalanches/mudslides/landslides, and extreme weather events could alter the age of menarche by disrupting food availability or via increased toxin/pollutant release. Overall, our review revealed that these perturbations in the timing of menarche are likely to increase the disease burden for women in four key areas: mental health, fertility-related conditions, cardiovascular disease, and bone health. In summary, the climate does have the potential to impact women’s health through perturbation in the timing of menarche and this, in turn, will affect women’s risk of disease in future.

Urinary cadmium and timing of menarche and pubertal development in girls

BackgroundCadmium (Cd) is a developmental toxicant that is released into the environment during industrial processes. Previous animal studies suggest that Cd may impact the onset of puberty. ObjectivesTo determine whether Cd exposure, measured as urinary Cd concentration, was associated with ages at menarche and pubertal development. MethodsA cohort of 211 girls, ages 10–13 years at baseline, was followed for up to two years. Girls completed an interview and self-assessment of Tanner stages of breast development and pubic hair growth. They were followed monthly until menarche. Urinary Cd concentrations were measured in overnight urine specimens. Multivariable Cox regression was used to evaluate the association between urinary Cd and age at menarche and cumulative logit regression was used to evaluate the associations between urinary Cd and breast development and pubic hair growth. ResultsThe baseline geometric mean creatinine-adjusted Cd concentration was 0.22 μg/g creatinine (geometric standard deviation = 1.6) and decreased with increasing age (p-trend = 0.04). Cd levels were higher among Asian than White girls or girls of other/mixed race/ethnicity (p = 0.04). In multivariable analyses, girls with urinary Cd ≥ 0.4 μg/L were less likely to have attained menarche than girls with urinary Cd < 0.2 μg/L (hazard ratio = 0.42; 95% confidence interval, 0.23–0.78). Urinary Cd was negatively associated with pubic hair growth (p-trend = 0.01) but not with breast development (p-trend = 0.72) at baseline. ConclusionsThese findings suggest that a higher Cd body burden may delay some aspects of pubertal development among girls.

Relationships of Lead, Mercury and Cadmium Levels with the Timing of Menarche among Korean Girls.

PurposeThis study utilized data from the Korean National Health and Nutrition Examination Survey (KNHANES) to explore differences in the timing of menarche in Korean girls according to blood heavy metal concentrations.MethodsThis study performed a secondary analysis of cross-sectional data from the sixth KNHANES. Data from 179 female children and adolescents aged 10~18 were included in this study. The relationships of blood heavy metal concentrations (lead, mercury, and cadmium) with age of menarche were analyzed using complex sample multiple logistic regression.ResultsIn the participants of this study, the geometric mean values of blood lead, mercury, and cadmium concentrations were 1.15±0.04 μg/dL, 1.80±0.08 μg/L, and 0.30±0.03 μg/L, respectively. Mercury poisoning (>5 μg/L) was found in 1.5% of participants. Furthermore, significant relationships were found between blood lead and mercury concentrations and age at menarche (p for trend: p<.001 and p=.015, respectively).ConclusionThrough an analysis of national big data, this study found evidence that Korean girls showed a younger age at menarche in response to higher blood lead and mercury concentrations. To prevent and manage precocious puberty in Korean children and adolescents, a systematic policy that monitors both exposure to environmental hazards and blood heavy metal concentrations is needed.

Evaluation of Abnormal Bleeding in Children

Abnormal bleeding or bruising is a relatively common clinical concern, frequently causing parents to seek care from their children's primary care provider. Although ecchymosis from playful trauma, occasional epistaxis, and heavy menstrual bleeding around the time of menarche and beyond are common occurrences, it can be difficult for pediatricians and other primary care providers to determine if their patient has age-appropriate symptoms versus abnormal or excessive bleeding. This review discusses considerations for abnormal bleeding in pediatrics and discusses an initial approach for evaluation of hemostasis in a child with bleeding symptoms. [Pediatr Ann. 2020;49(1):e36-e42.].

Declining ages at menarche in an agrarian rural region of Poland.

Age at menarche in Poland has varied with political and socioeconomic changes. An increase in age at menarche corresponded to a period of economic crisis and food rationing between 1976 and 1989. Experiencing food shortages in utero or during childhood development can affect menarcheal timing, but this national effect may be buffered in local agrarian regions growing their own food. Here we examine patterns of age at menarche over time in the rural, agrarian Beskid Wyspowy region of southern Poland. This study examined menarcheal timing using data collected from Polish women (n = 1326) recruited at the Mogielica Human Ecology Study Site between 2003 and 2018. Simple linear regressions were used to assess changing ages at menarche over time. Comparisons between ages at menarche for women born before and after the fall of communism in 1989 were assessed via one-way analysis of variance. Age at menarche has declined over time in the Beskid Wyspowy region of southern Poland from 1920 to 2000 (R2 = .08, P < .0001). There was not a statistically significant increase or decrease in age at menarche for women born and growing up during the period of food rationing. The declining age at menarche is likely reflective of a transitioning environment, suggesting that major socioeconomic changes affect life history traits like pubertal timing. Living in agricultural regions may have helped buffer the increasing ages at menarche seen in other areas of Poland during times of food rationing.