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1.  Earlier Mother's Age at Menarche Predicts Rapid Infancy Growth and Childhood Obesity 
PLoS Medicine  2007;4(4):e132.
Background
Early menarche tends to be preceded by rapid infancy weight gain and is associated with increased childhood and adult obesity risk. As age at menarche is a heritable trait, we hypothesised that age at menarche in the mother may in turn predict her children's early growth and obesity risk.
Methods and Findings
We tested associations between mother's age at menarche, mother's adult body size and obesity risk, and her children's growth and obesity risk in 6,009 children from the UK population-based Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort who had growth and fat mass at age 9 y measured by dual-energy X-ray absorptiometry. A subgroup of 914 children also had detailed infancy and childhood growth data. In the mothers, earlier menarche was associated with shorter adult height (by 0.64 cm/y), increased weight (0.92 kg/y), and body mass index (BMI, 0.51 kg/m2/y; all p < 0.001). In contrast, in her children, earlier mother's menarche predicted taller height at 9 y (by 0.41 cm/y) and greater weight (0.80 kg/y), BMI (0.29 kg/m2/y), and fat mass index (0.22 kg/m2/year; all p < 0.001). Children in the earliest mother's menarche quintile (≤11 y) were more obese than the oldest quintile (≥15 y) (OR, 2.15, 95% CI 1.46 to 3.17; p < 0.001, adjusted for mother's education and BMI). In the subgroup, children in the earliest quintile showed faster gains in weight (p < 0.001) and height (p < 0.001) only from birth to 2 y, but not from 2 to 9 y (p = 0.3–0.8).
Conclusions
Earlier age at menarche may be a transgenerational marker of a faster growth tempo, characterised by rapid weight gain and growth, particularly during infancy, and leading to taller childhood stature, but likely earlier maturation and therefore shorter adult stature. This growth pattern confers increased childhood and adult obesity risks.
Earlier age at menarche may be a transgenerational marker of faster growth, particularly during infancy, leading to taller childhood stature but earlier maturation and hence shorter adult stature.
Editors' Summary
Background.
Childhood obesity is a rapidly growing problem. Twenty-five years ago, overweight children were rare. Now, 155 million of the world's children are overweight and 30–45 million are obese. Overweight and obese children—those having a higher than average body mass index (BMI; weight divided by height squared) for their age and sex—are at increased risk of becoming obese adults. Such people are more likely to develop heart disease, diabetes, and other health problems than lean people. Many factors are involved in the burgeoning size of children. Parental obesity, for example, predisposes children to being overweight. In part, this is because parents influence the eating habits of their offspring and the amount of exercise they do. In addition, though, children inherit genetic factors from their parents that make them more likely to put on weight.
Why Was This Study Done?
To prevent childhood obesity, health care professionals need ways to predict which infants are likely to become obese so that they can give parents advice on controlling their children's weight. In girls, early menarche (the start of menstruation) is associated with an increased risk of childhood and adult obesity and tends to be preceded by rapid weight gain in the first two years of life. Because age at menarche is inherited, the researchers in this study have investigated whether mothers' age at menarche predicts rapid growth in infancy and childhood obesity in their offspring using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). In 1991–1992, this study recruited nearly 14,000 children born in Bristol, UK. Since then, the children have been regularly examined to investigate how their environment and genetic inheritance interact to affect their health.
What Did the Researchers Do and Find?
The researchers measured the growth and fat mass of 6,009 children from ALSPAC at 9 years of age. For 914 of these children, the researchers had detailed data on their growth during infancy and early childhood. They then looked for any associations between the mother's age at menarche (as recalled during pregnancy), mother's adult body size, and the children's growth and obesity risk. In the mothers, earlier menarche was associated with shorter adult height and increased weight and BMI. In the children, those whose mothers had earlier menarche were taller and heavier than those whose mothers had a later menarche. They also had a higher BMI and more body fat. The children whose mothers had their first period before they were 11 were twice as likely to be obese as those whose mothers did not menstruate until they were 15 or older. Finally, for the children with detailed early growth data, those whose mothers had the earliest menarche had faster weight and height gains in the first two years of life (but not in the next seven years) than those whose mothers had the latest menarche.
What Do These Findings Mean?
These findings indicate that earlier mother's menarche predicts a faster growth tempo (the speed at which an individual reaches their adult height) in their offspring, which is characterized by rapid weight and height gain during infancy. This faster growth tempo leads to taller childhood stature, earlier sexual maturity, and—because age at puberty determines adult height—shorter adult stature. An inherited growth pattern like this, the researchers write, confers an increased risk of childhood and adult obesity. As with all studies that look for associations between different measurements, these findings will be affected by the accuracy of the measurements—for example, how well the mothers recalled their age at menarche. Furthermore, because puberty, particularly in girls, is associated with an increase in body fat, a high BMI at age nine might indicate imminent puberty rather than a risk of long-standing obesity—further follow-up studies will clarify this point. Nevertheless, the current findings provide a new factor—earlier mother's menarche—that could help health care professionals identify which infants require early growth monitoring to avoid later obesity.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040132.
The Avon Longitudinal Study of Parents and Children has a description of the study and results to date
The US Centers for Disease Control and Prevention provides information on overweight and obesity (in English and Spanish)
US Department of Health and Human Services's program, Smallstep Kids, is an interactive site for children about healthy eating (in English and Spanish)
The International Obesity Taskforce has information on obesity and its prevention
The World Heart Federation's Global Prevention Alliance provides details of international efforts to halt the obesity epidemic and its associated chronic diseases
The Child Growth Foundation has information on childhood growth and its measurement
doi:10.1371/journal.pmed.0040132
PMCID: PMC1876410  PMID: 17455989
2.  Early life soy exposure and age at menarche 
SUMMARY
This study examines the timing of menarche in relation to infant feeding methods, specifically addressing the potential effects of soy isoflavone exposure through soy-based infant feeding. Subjects were participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers were enrolled during pregnancy and their children have been followed prospectively. Early life feeding regimes, categorized as primarily breast, early formula, early soy, and late soy were defined using infant feeding questionnaires administered during infancy. For this analysis, age at menarche was assessed through questionnaires administered approximately annually between ages 8 and 14.5. Eligible subjects were limited to term, singleton, white females. We used Kaplan-Meier survival curves and Cox proportional hazards models to assess age at menarche and risk of menarche over the study period.
The present analysis included 2,920 girls. Approximately 2% of mothers reported that soy products were introduced into the infant diet at or before 4 months of age (early soy). The median age at menarche [interquartile range (IQR)] in the study sample was 153 months [144–163], approximately 12.8 years. The median age at menarche among early soy fed girls was 149 months (12.4 years) [IQR, 140–159]. Compared to girls fed non-soy based infant formula or milk (early formula), early soy fed girls were at 25% higher risk of menarche throughout the course of follow up (Hazard Ratio 1.25 [95% confidence interval, 0.92, 1.71]). Our results also suggest that girls fed soy products in early infancy may have an increased risk of menarche specifically in early adolescence. These findings may be the observable manifestation of mild endocrine disrupting effects of soy isoflavone exposure. However, our study is limited by few soy-exposed subjects and is not designed to assess biological mechanisms. Because soy formula use is common in some populations, this subtle association with menarche warrants more indepth evaluation in future studies.
doi:10.1111/j.1365-3016.2011.01244.x
PMCID: PMC3443957  PMID: 22324503
3.  Prenatal and infant exposures and age at menarche 
Epidemiology (Cambridge, Mass.)  2013;24(2):277-284.
Background
Early menarche is related to increased risk of breast cancer. The number of established factors that contribute to early menarche is limited. We studied prenatal and infant exposures in relation to age at menarche in a nationwide cohort of women who have a family history of breast cancer.
Methods
The study comprised 33,501 women in the Sister Study who were aged 35-59 years at baseline (2003-2009). We used polytomous logistic regression to estimate separate relative risk ratios (rRRs) and 95% confidence intervals (CIs) for associations of self-reported exposures with menarche at ≤10, 11, 14, and ≥15 years relative to menarche at 12-13 years.
Results
Early menarche (≤10 or 11 years) was associated with having low birth weight, having had a teenage mother, being firstborn, and specific maternal prenatal exposures: smoking, DES (diethylstilbestrol), pre-pregnancy diabetes, and pregnancy-related hypertensive disorder. Prenatal exposures most strongly associated with very early menarche (≤10 years) were DES (rRR = 1.56 [95% CI = 1.24-1.96]), maternal pre-pregnancy diabetes (2.24 [1.37-3.68]), and pregnancy-related hypertensive disorder (1.45 [1.18-1.79]). Soy formula was associated with both very early menarche (1.21 [0.94-1.54]) and late menarche (14 years: 1.17 [0.98-1.40] or ≥15 years: 1.28 [1.06-1.56]).
Conclusions
Although menarche is only one marker of pubertal development, it is a commonly used surrogate. The observed associations of prenatal DES and soy formula exposure with age at menarche are consistent with animal data on exogenous estrogens and pubertal timing. Early-life exposures may confound associations between age at menarche and hormonally dependent outcomes in adults.
doi:10.1097/EDE.0b013e31828062b7
PMCID: PMC3563843  PMID: 23348069
4.  Age at menarche in the Korean female: secular trends and relationship to adulthood body mass index 
Purpose
The objective of this study is to estimate the trend in age at menarche in the Korean female and evaluate the relationship between age at menarche and adult body mass index (BMI), which is a indicator of later-life health.
Methods
We conducted a cross-sectional analysis of a nationally representative sample (self-reported age at menarche and measured height and weight) of 11,065 females aged 15 and older. Data were obtained from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV, 2007-2009).
Results
We found a statistically significant decline in age at menarche in successive birth groups, indicating a 0.726 year decrease per decade. The age at menarche in 1990-1994 year birth group was 12.60 years, which showed a significant decreased from 3.11 years in the 1980-1984 birth group. We also found a significant negative association between age at menarche and current BMI. A one-year decrease in age at menarche was associated with mean BMI increase of 0.109 kg/m2 (95% confidence interval [CI], 0.069 to 0.150) after adjustment for age. In multivariate logistic regression, the odds ratios of obesity in females with early menarche (<12 years) was 1.845 fold (95% CI, 1.441 to 2.361).
Conclusion
We found that age at menarche is still falling in the Korean female. We also found that early menarche is a risk factor for obesity in adults.
doi:10.6065/apem.2013.18.2.60
PMCID: PMC4027094  PMID: 24904853
Body mass index; Epidemiology; Menarche; Obesity; Korean
5.  Prenatal and childhood environmental tobacco smoke exposure and age at menarche 
Previous studies have reported mixed results regarding the association between age at menarche and environmental tobacco smoke exposure, both prenatally and during early childhood; however, few studies have had data available during both time periods. The present study examined whether exposure to prenatal tobacco smoke (PTS) via maternal smoking during pregnancy or childhood environmental tobacco smoke (ETS) was associated with age at menarche in a multi-ethnic birth cohort. With the uniquely available prospectively collected data on body size and growth at birth and in early life, we further examined whether the association between PTS and ETS exposure and age at menarche was mediated by these variables. From 2001 to 2006, we recruited 262 women born between 1959 and 1963 who were enrolled previously in a New York City site of the National Collaborative Perinatal Project. Mothers who smoked during pregnancy vs. those who did not were more likely to be White, younger, have more education and have lower birthweight babies. Daughters with heavy PTS exposure (≥20 cigarettes per day) had a later age at menarche (>12 years vs. ≤12 years), odds ratio (OR) = 2.1 [95% confidence interval (CI) 0.9, 5.0] compared with daughters with no PTS. Daughters exposed to only childhood ETS had a later age at menarche, OR = 2.1 [95% CI 1.0, 4.3], and those exposed to PTS and ETS combined had a statistically significant later age at menarche, OR = 2.2 [95% CI 1.1, 4.6] compared with daughters with no PTS and no ETS. These results did not change after further adjustment for birthweight and postnatal growth suggesting that exposure to PTS and ETS is associated with later age at menarche even after considering possible relationships with growth.
doi:10.1111/j.1365-3016.2010.01154.x
PMCID: PMC3070941  PMID: 20955229
menarche; puberty; maternal prenatal smoking; childhood environmental tobacco smoke
6.  The influence of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer 
Breast Cancer Research : BCR  2008;10(6):R107.
Introduction
Hormonal factors are implicated in tumor progression and it is possible that factors influencing breast cancer induction could affect prognosis. Our study investigated the effects of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer.
Methods
We used a nationwide, population-based, case-case design of 2,640 Swedish women who were 50 to 74 years old and had postmenopausal breast cancer during 1993 to 1995. Follow-up was conducted until 31 December 2000. We used polytomous multiple logistic regression to investigate the relationships between menstrual factors (age at menarche, cycle length, irregular menstruation, lifetime number of menstrual cycles, and age at menopause), tumor characteristics (size, grade, estrogen receptor and progesterone receptor [PR] status, lymph node involvement, and histology), and Cox proportional hazards modeling for 5-year survival.
Results
Younger ages at menarche were significantly associated with grade and lymph node involvement. Women with an age at menarche of 11 years or younger had a more than twofold excess risk of medium-grade (odds ratio [OR] = 2.05; 95% confidence interval [CI] 1.00 to 4.18) and high-grade (OR = 2.04; 95% CI 1.01 to 4.16) tumors. Early menarche significantly increased the risk of lymph node metastases. Survival was poorest in women with the earliest age at menarche, with a 72% increased risk of dying within 5 years after diagnosis (hazard ratio = 1.72; 95% CI 1.02 to 2.89). No significant associations were observed for other menstrual factors with tumor characteristics or survival.
Conclusions
Age at menarche has a significant impact on breast cancer prognosis and survival. It remains to be established whether the associations are attributable to age at menarche directly or are associated with the early-life physiological events of breast development and carcinogenesis also taking place during childhood and puberty, as menarche is only the culmination of this series of events.
doi:10.1186/bcr2212
PMCID: PMC2656904  PMID: 19087323
7.  Association of age at menarche with metabolic syndrome and its components in rural Bangladeshi women 
Background
Early age at menarche is associated with increased risk of metabolic syndrome in both China and the West. However, little is known about the impact of age at menarche and metabolic syndrome in South Asian women, including those from low-income country, where age at menarche is also falling. The aim of the present study was to investigate whether age at menarche is inversely associated with metabolic syndrome in Bangladeshi women, who are mostly poor and have limited access to and or poor health care facilities.
Methods
This community-based cross-sectional study was performed using 1423 women aged between 15–75 years from rural Bangladesh in 2009 and 2010. Metabolic syndrome was defined according to standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between age at menarche and metabolic syndrome, with adjustment of potential confounding variables, including age, education, marital status, tobacco users, use of contraceptives and number of pregnancies.
Results
Early onset of menarche (<12 years) as compared to late onset (>13 years) was found to be associated with a higher prevalence of metabolic syndrome (odds ratio=1.55; 95 % confidence interval =1.05-2.30). Age at onset of menarche was also inversely associated with prevalence of high triglycerides (P for trend <0.01) and low high-density lipoprotein cholesterol (P for trend = 0.01), but positively associated with prevalence of high fasting blood glucose (P for trend =0.02). However, no significant association was found between age at menarche, high blood pressure and elevated waist circumference.
Conclusion
Early onset of menarche might promote or trigger development of metabolic syndrome. Thus, knowledge of the history of age at onset of menarche may be critical in identifying women at risk of developing metabolic syndrome and those likely to benefit the most from early interventions.
doi:10.1186/1743-7075-9-99
PMCID: PMC3541253  PMID: 23140264
Age at menarche; Metabolic syndrome; Women; Rural Bangladesh
8.  Diet, body size and menarche in a multiethnic cohort 
British Journal of Cancer  1999;79(11-12):1907-1911.
A multiethnic cohort of 1378 Southern California school girls aged 8–13 years was followed for 4 years to evaluate factors predicting age at menarche, a risk factor for breast cancer. Height and weight were measured and dietary intake was assessed using a semi-quantitative food frequency questionnaire. Of 939 girls providing data on menarcheal status, 767 were premenarcheal at the start of the study; 679 girls provided acceptable dietary data and were included in the analyses. Cox proportional hazards models were used to assess the relationship between diet, body size, ethnicity and age at menarche. Hispanic, Asian/Pacific Island and African-American girls were more likely to experience early menarche than non-Hispanic white girls. Tall (> 148.6 cm) versus short (< 135.9 cm) girls experienced earlier menarche (relative hazard (RH) = 2.9, 95% confidence interval (CI) 2.1–4.1) as did those with high Quetelet's index (QI, kg m−2) (> 20.7) versus low QI (< 16.1) (RH = 2.2, 95% CI 1.7–2.9). Of all the dietary variables analysed, only energy intake was related to age at menarche. High versus low energy intake (> 12013 kJ vs < 7004 kJ) was associated with a delay in menarche (RH = 0.7, 95% CI 0.5–0.9); this finding was limited to a subset of heavy Hispanic girls who appeared to underreport their dietary intake. © 1999 Cancer Research Campaign
doi:10.1038/sj.bjc.6690303
PMCID: PMC2362774  PMID: 10206312
menarche; diet; height; body mass index
9.  Anthropometry and Menarcheal Status of Adolescent Nigerian Urban Senior Secondary School Girls 
Background
Age at menarche is a significant indicator of growth and sexual maturation in girls. During adolescence, anthropometry provides a tool for monitoring and evaluating the hormone-mediated changes in growth and reproductive maturation.
Objectives
We aimed to examine the anthropometric status of pre- and post-menarcheal Nigerian adolescent girls attending senior secondary schools.
Materials and Methods
In this school-based cross-sectional survey, a pre-tested structured self-administered questionnaire was set for obtaining the socio-demographic data (age at menarche, number of siblings, occupation and educational attainment of their parents, etc.), while the anthropometric status data was obtained by direct measurement of weight and height. The body mass index (BMI) and the ponderal index (PI) of each participant were computed from their respective weight and height values. The study was designed to include all the students in the two schools that were randomly selected. The anthropometric indices of pre- and post-menarcheal girls were compared.
Results
Out of a total population of 2,166 students, 2,159 (99.7%) participated but 9 questionnaires were incompletely filled and were rejected, leaving 2,150 (510 were pre-menarcheal and 1,640 were post- menarcheal) for further analysis. The mean menarcheal age was 13.44 ± 1.32 years (95% Confidence Interval (CI) = 13.38-13.5). Girls from families with high socio-economic status (SES) attained menarche 8.0 and 9.0 months earlier than their counterparts from families with middle and low SES respectively. Girls from small-size families had a significantly lower menarcheal age than their counterparts from large-size families. A comparison of the anthropometric indices of pre- and post-menarcheal girls showed: weight, 41.1 ± 6.3 kg (95% CI = 40.6-41.6) vs 47.6 ± 7.2 kg (95% CI = 47.3-47.9), P < 0.001; height, 146.2± 5.5 cm (95% CI = 145.7-146.7) vs 153.6 ± 9.9 cm (95% CI = 153.1-154.1), P < 0.001; BMI, 16.4 ± 1.9 (95% CI = 16.2-16.6) vs 18.8 ± 1.6 (95% CI = 18.7-18.9), P < 0.001; and PI, 45.1 ± 1.7 (95% CI = 45.0-45.2) vs 44.6 ± 1.4 (95% CI = 44.5-44.7), P < 0.01.
Conclusions
Post-menarcheal girls were significantly taller and heavier with a higher BMI than their pre-menarcheal counterparts, but the pre-menarcheal girls possessed a better linear body as reflected by the PI.
doi:10.5812/ijem.8052
PMCID: PMC3693660  PMID: 23825976
Body Mass Index; Height; weight; Ponderal Index; Menarche
10.  Food insecurity and age at menarche among adolescent girls in Jimma Zone Southwest Ethiopia: a longitudinal study 
Background
Age at menarche is the reflection of cumulative pre-adolescent exposure of girls to either adverse environment such as food insecurity or affluent living conditions. Food insecurity could result in inadequate nutrient intake and stress, both of which are hypothesized to have opposing effects on the timing of menarche through divergent pathways. It is not known whether food insecure girls have delayed menarche or early menarche compared with their food secure peers. In this study we test the competing hypothesis of the relationship between food insecurity and age at menarche among adolescent girls in the Southwest Ethiopia.
Methods
We report on 900 girls who were investigated in the first two rounds of the five year longitudinal survey. The semi-parametric frailty model was fitted to determine the effect of adolescent food insecurity on time to menarche after adjusting for socio-demographic and economic variables.
Results
Food insecure girls have menarche one year later than their food secure peer (median age of 15 years vs 14 years). The hazard of menarche showed a significant decline (P = 0.019) as severity of food insecurity level increased, the hazard ratio (HR) for mild food insecurity and moderate/severe food insecurity were 0.936 and 0.496, respectively compared to food secure girls. Stunted girls had menarche nearly one year later than their non-stunted peers (HR = 0.551, P < 0.001).
Conclusion
Food insecurity is associated with delay of age at menarche by one year among girls in the study area. Stunted girls had menarche one year later than their non-stunted peers. Age at menarche reflects the development of girls including the timing of sexual maturation, nutritional status and trajectory of growth during the pre-pubertal periods. The findings reflect the consequence of chronic food insecurity on the development and well-being of girls in the study area.
doi:10.1186/1477-7827-9-125
PMCID: PMC3180361  PMID: 21910910
11.  Earlier menarche is associated with a higher prevalence of Herpes simplex type-2 (HSV-2) in young women in rural Malawi 
eLife  2014;3:e01604.
Remarkably little is known about associations between age at menarche and sexually transmitted infections, although girls with earlier menarche tend to have earlier sexual debut and school drop-out, so an association might be expected. In a population-based survey of >3000 women aged 15–30 in northern Malawi we show that those with earlier menarche had earlier sexual debut, earlier marriage and were more often Herpes simplex type-2 (HSV-2) positive. Compared to those with menarche aged <14, the age-adjusted odds ratios for HSV-2 were 0.89 (95%CI 0.71–1.1), 0.71 (0.57–0.89) and 0.69 (0.54–0.89) for menarche aged 14, 15 and 16+ respectively. This association persisted after adjusting for socio-economic factors, including schooling, and for sexual behaviour. No such association was seen with HIV infection, which is much less common and less uniformly distributed than HSV-2 in this population. The extra vulnerability of girls with earlier menarche needs to be recognised.
DOI: http://dx.doi.org/10.7554/eLife.01604.001
eLife digest
For many girls in sub-Saharan Africa their first menstrual cycle can mean an abrupt end to childhood because a girl’s first period is often taken as a signal that she is ‘ready’ for sex and marriage. Most girls in this region have their first menstrual cycle between the ages of 13 and 18, with the median being around 15, and this is likely to get earlier as nutrition improves.
The age at which a girl in sub-Saharan Africa has her first period can have dramatic effects on her future prospects. Previous research in rural Malawi showed that more than half of those young women who had their first period before their 14th birthday never finish primary school and have sex before they are 16 years old. By comparison, 70% of women whose first menstrual cycle occurs at age 16 or older finish primary school and delay sex until after age 18.
To assess whether early menstruation might also be associated with the risk of contracting a sexually transmitted infection, Glynn et al. surveyed more than 3000 women between the ages of 15 and 30 in northern Malawi. Women who had their first menstrual cycle at an older age were less likely than those with an earlier onset of menstruation to be infected with Herpes simplex type-2. This difference persisted after adjustment for age at first sex and marriage, and for differences in socio-economic position, education and number of sexual partners. This may suggest that women with earlier onset of menstruation tended to have higher risk partnerships. There was no relationship between HIV and age at first menstrual cycle, probably because HIV is much less common than Herpes in the areas where the women lived.
Community and individual level interventions are needed to encourage and enable adolescent girls with early onset of menstruation to stay in school throughout puberty and beyond, and to help them reduce sexual risk taking from before their first sexual experiences.
DOI: http://dx.doi.org/10.7554/eLife.01604.002
doi:10.7554/eLife.01604
PMCID: PMC3901398  PMID: 24473074
Herpes simplex type 2; sexual health; Africa; Human
12.  Childhood Abuse and Age at Menarche 
Purpose
Physical and sexual abuse are prevalent social hazards. We sought to examine the association between childhood physical and sexual abuse and age at menarche.
Methods
Among 68,505 participants enrolled in the Nurses’ Health Study II we investigated the association between childhood physical abuse and sexual abuse on menarche prior to age 11 (early) or after age 15 (late) using multivariate logistic regression analysis, mutually adjusting for both types of abuse.
Results
Fifty-seven percent of respondents reported some form of physical or sexual abuse in childhood. We found a positive dose-response association between severity of sexual abuse in childhood and risk for early menarche. Compared to women who reported no childhood sexual abuse, the adjusted odds ratio [AOR] for early menarche was 1.20 (95% confidence interval [CI], 1.10, 1.37) for sexual touching and 1.49 (95% CI, 1.34, 1.66) for forced sexual activity. Only severe physical abuse predicted early menarche (AOR=1.22, 95% CI, 1.10–1.37). Childhood physical abuse had a dose-response association with late age at menarche: AOR 1.17 (95% CI, 1.04, 1.32) for mild, 1.20 (95% CI, 1.08, 1.33) for moderate, and 1.50 (95% CI, 1.27, 1.77) for severe physical abuse. Sexual abuse was not associated with late menarche.
Conclusion
Childhood abuse was very prevalent in this large cohort of U.S. women. Severity of childhood sexual abuse was associated with risk for early onset of menarche, and physical abuse was associated with both early and late onset menarche.
Implications and Contribution
The severity of childhood sexual abuse and severe physical abuse were associated with risk for accelerated menarche, while severity of childhood physical was associated with risk for delayed onset of menarche. The nature of the association between different forms of childhood adversities and reproductive lifespan may vary.
doi:10.1016/j.jadohealth.2012.06.006
PMCID: PMC3950206  PMID: 23332491
menarche; adversities; child abuse; emotional support
13.  Exposures to Endocrine-Disrupting Chemicals and Age of Menarche in Adolescent Girls in NHANES (2003–2008) 
Environmental Health Perspectives  2012;120(11):1613-1618.
Background: The observed age of menarche has fallen, which may have important adverse social and health consequences. Increased exposure to endocrine-disrupting compounds (EDCs) has been associated with adverse reproductive outcomes.
Objective: Our objective was to assess the relationship between EDC exposure and the age of menarche in adolescent girls.
Methods: We used data from female participants 12–16 years of age who had completed the reproductive health questionnaire and laboratory examination for the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey (NHANES) for years 2003–2008 (2005–2008 for analyses of phthalates and parabens). Exposures were assessed based on creatinine-corrected natural log urine concentrations of selected environmental chemicals and metabolites found in at least 75% of samples in our study sample. We used Cox proportional hazards analysis in SAS 9.2 survey procedures to estimate associations after accounting for censored data among participants who had not reached menarche. We evaluated body mass index (BMI; kilograms per meter squared), family income-to-poverty ratio, race/ethnicity, mother’s smoking status during pregnancy, and birth weight as potential confounders.
Results: The weighted mean age of menarche was 12.0 years of age. Among 440 girls with both reproductive health and laboratory data, after accounting for BMI and race/ethnicity, we found that 2,5-dichlorophenol (2,5-DCP) and summed environmental phenols (2,5-DCP and 2,4-DCP) were inversely associated with age of menarche [hazard ratios of 1.10; 95% confidence interval (CI): 1.01, 1.19 and 1.09; 95% CI: 1.01, 1.19, respectively]. Other exposures (total parabens, bisphenol A, triclosan, benzophenone-3, total phthalates, and 2,4-DCP) were not significantly associated with age of menarche.
Conclusions: Our findings suggest an association between 2,5-DCP, a potential EDC, and earlier age of menarche in the general U.S. population.
doi:10.1289/ehp.1104748
PMCID: PMC3556609  PMID: 23124194
2,4-dichlorophenol; endocrine disruptors; menarche; NHANES; reproductive health
14.  Abnormal Timing of Menarche in Survivors of Central Nervous System Tumors: A Report From The Childhood Cancer Survivor Study 
Cancer  2009;115(11):2562-2570.
Background
Children who receive high dose radiation therapy to the hypothalamic-pituitary axis may be at risk for both early and late puberty. Data on risk of altered timing of menarche after higher dose RT, as used in the treatment of CNS tumors, are limited.
Patients & Methods
We evaluated 235 female survivors of CNS tumors, diagnosed between 1970-1986, and >1,000 sibling controls who were participants in the Childhood Cancer Survivor Study, and provided self-reported data on age at menarche.
Results
Survivors of CNS tumors were more likely to have onset of menarche before age ten compared to their siblings (11.9% vs. 1.0%) (Odds Ratio [OR] =14.1, 95% confidence interval [95% CI] 7.0-30.9). Of the 138 survivors who received RT to the HP axis, 20 (14.5%) had onset of menarche before age 10, compared to 4.3% of those who did not receive RT (OR=3.8, 95% CI=1.2-16.5). Age ≤4 years at diagnosis was associated with an increased risk (OR=4.0, 95% CI=1.7-10.0) of early menarche. Additionally, survivors of CNS tumors were more likely than siblings to have onset of menarche after age 16 (10.6% vs. 1.9%) (OR=6.6, 95% CI=3.4-11.4). Doses of RT to the H-P axis >50 Gy (OR=9.0, 95% CI 2.3-59.5) and spinal RT conferred an increased risk of late menarche, as did older age (>10 years) at the time of diagnosis (OR = 3.0, 95% CI 1.3-7.0).
Conclusion
Survivors of CNS tumors are at significant risk of both early and late menarche associated with RT exposure and age at treatment.
doi:10.1002/cncr.24294
PMCID: PMC2746632  PMID: 19309737
menarche; puberty; late-effects; brain tumor; pediatric
15.  Age at Menarche, Schooling, and Sexual Debut in Northern Malawi 
PLoS ONE  2010;5(12):e15334.
Background
Age at sexual debut is a key behavioural indicator used in HIV behavioural surveillance. Early age at menarche may precipitate early sex through perceived readiness for sex, or through school drop-out, but this is rarely studied. We investigated trends and circumstances of sexual debut in relation to schooling and age at menarche.
Methods and Findings
A cross-sectional sexual behaviour survey was conducted on all individuals age 15–59 within a demographic surveillance site in Karonga District, Malawi. Time trends were assessed using birth cohorts. Survival analysis was used to estimate the median age at menarche, sexual debut and first marriage. The 25th centile was used to define “early” sex, and analyses of risk factors for early sex were restricted to those who had reached that age, and were done using logistic regression. Of the 8232 women and 7338 men resident in the area, 88% and 78%, respectively, were seen, and, 94% and 92% of these were interviewed. The median reported age at first sex was 17.5 for women and 18.8 for men. For women, ages at menarche, sexual debut and first marriage did not differ by birth cohort. For men, age at sexual debut and first marriage decreased slightly in later birth cohorts. For both men and women increased schooling was associated with later sexual debut and a longer delay between sexual debut and first marriage, but the associations were stronger for women. Earlier age at menarche was strongly associated with earlier sexual debut and marriage and lower schooling levels. In women early sexual debut (<16 years) was less likely in those with menarche at age 14–15 (odds ratio (OR) 0.31, 95%CI 0.26–0.36), and ≥16 (OR 0.04, 95%CI 0.02–0.05) compared to those with menarche at <14. The proportion of women who completed primary school was 46% in those with menarche at <14, 60% in those with menarche at 14–15 and 70% in those with menarche at ≥16. The association between age at menarche and schooling was partly explained by age at sexual debut. The association between age at menarche and early sex was not altered by adjusting for schooling.
Conclusions
Women with early menarche start sex and marry early, leading to school drop-out. It is important to find ways to support those who reach menarche early to access the same opportunities as other young women.
doi:10.1371/journal.pone.0015334
PMCID: PMC3000342  PMID: 21151570
16.  Gestational Weight Gain and Daughter's Age at Menarche 
Journal of Women's Health  2011;20(8):1193-1200.
Abstract
Background
Sexual development begins in utero and enters a dormant phase during infancy. The influence of maternal gestational weight gain (GWG) on daughter's age at menarche has not been explored.
Methods
We investigated the association between maternal GWG and age at menarche (<11 years, 11–15 years, >15 years of age) in a large cohort study of U.S. nurses, The Nurses' Health Study II (NHS II), and the Nurses' Mothers' Cohort Study.
Results
Among 32,218 respondents, 7% reported age at menarche age 15. Compared with women whose mothers gained 20–29 lbs during pregnancy, those whose mothers reported <10 lbs or >40 lbs of GWG were 30% more likely to report early onset menarche (<11 years of age) in logistic regression models adjusted for sociodemographic and maternal characteristics, and childhood body size and physical activity: adjusted odds ratio (OR) 1.31, 95% confidence interval (CI) 1.05-1.62, and 1.27, 95% CI 1.06-1.56. Maternal GWG was not associated with late menarche in the fully adjusted model (ptrend=0.07).
Conclusions
These results suggest that either extreme of maternal GWG may influence risk for early age at menarche in daughters. Maternal GWG may be a modifiable risk factor for early menarche.
doi:10.1089/jwh.2010.2517
PMCID: PMC3153868  PMID: 21711153
17.  African-American/White Differences in the Age of Menarche: Accounting for the Difference 
Social science & medicine (1982)  2012;75(7):1263-1270.
Lifetime health disparity between African-American and white females begins with lower birthweight and higher rates of childhood overweight. In adolescence, African-American girls experience earlier menarche. Understanding the origins of these health disparities is a national priority. There is growing literature suggesting that the life course health development model is a useful framework for studying disparities. The purpose of this study was to quantify the influence of explanatory factors from key developmental stages on the age of menarche and to determine how much of the overall race difference in age of menarche they could explain. The factors were maternal age of menarche, birthweight, poverty during early childhood (age 0 through 5 years), and child BMI z-scores at 6 years. The sample, drawn from the US National Longitudinal Surveys of Youth Child-Mother file, consisted of 2337 girls born between 1978 and 1998. Mean age of menarche in months was 144 for African-American girls and 150 for whites.
An instrumental variable approach was used to estimate a causal effect of child BMI z-score on age of menarche. The instrumental variables were prepregnancy BMI, high gestational weight gain and smoking during pregnancy. We found strong effects of maternal age of menarche, birthweight, and child BMI z-score (−5.23, 95% CI [−7.35,−3.12]) for both African-Americans and whites. Age of menarche declined with increases in exposure to poverty during early childhood for whites. There was no effect of poverty for African-Americans. We used Oaxaca decomposition techniques to determine how much of the overall race difference in age of menarche was attributable to race differences in observable factors and how much was due to race dependent responses. The African-American/white difference in childhood BMI explained about 18% of the overall difference in age of menarche and birthweight differences explained another 11%.
doi:10.1016/j.socscimed.2012.05.018
PMCID: PMC3407312  PMID: 22726619
USA; race disparities; menarche; childhood BMI; instrumental variables; age; girls
18.  Timing of Menarche and the Origins of Conduct Disorder 
Archives of general psychiatry  2006;63(8):890-896.
Context
Precocious onset of menses (ie, age ≤11 years) has repeatedly been identified as a risk factor for higher rates of delinquency or conduct disorder (CD) in girls. Although this association is often conceptualized as environmentally mediated (via processes such as affiliation of early-menstruating youth with older, more deviant peers), such conclusions are premature as biological and genetic explanations have yet to be fully considered.
Objective
To uncover the origins of the association between CD and timing of menarche.
Design, Setting, and Participants
The sample consisted of a population-based birth cohort of 708 mid-adolescent female twins assessed as part of the ongoing Minnesota Twin Family Study. We conducted 2 sets of analyses: standard bivariate analyses to uncover possible common genes and moderator analyses to evaluate possible moderation of genetic influences on CD by timing of menarche.
Main Outcome Measures
Conduct disorder was assessed via individual semistructured interviews with mothers and adolescents. Menarcheal status and age at menarche were assessed via the Pubertal Development Scale.
Results
The results argued against common genetic influences but did provide evidence of etiological moderation of CD by timing of menarche. The heritability of CD was strongest (67%) in girls with average timing of menarche (ie, age 12–13 years) and substantially weaker (8%) in those with early onset. Those with late initiation of menses (ie, age >13 years) similarly exhibited weaker genetic influences (29%). Shared environmental influences showed the opposite pattern, as they were far stronger for those with precocious and delayed onset vs those with average onset.
Conclusions
Our findings provide indirect support for psychosocial interpretations of the impact of precocious menarche and, to a lesser extent, delayed menarche on CD development. Further, they lend support to the notion that in some cases, genetic influences on psychopathology may be strongest in the “average, expectable” environment.
doi:10.1001/archpsyc.63.8.890
PMCID: PMC2242428  PMID: 16894065
19.  Childhood Abuse and Early Menarche: Findings From the Black Women’s Health Study 
American journal of public health  2009;99(Suppl 2):S460-S466.
Objectives
We examined the association between childhood abuse and early menarche in a sample of US Black women.
Methods
We conducted multivariable log-binomial regression on data from 35330 participants in the Black Women’s Health Study to estimate risk ratios and 95% confidence intervals for the relation of childhood physical and sexual abuse with early age at menarche (i.e., <12 years).
Results
In adjusted analyses, sexual abuse was positively associated with early menarche, and the risk of early menarche increased with increasing frequency of sexual abuse incidents. We observed a weak but statistically significant association between physical abuse and early menarche. Associations between sexual abuse and early menarche were stronger when we used a more stringent cutpoint for early menarche (i.e., <11 years).
Conclusions
Our data suggest an increased risk of early menarche among Black women who experienced childhood sexual abuse. Evidence for an association between childhood physical abuse and early menarche was equivocal.
doi:10.2105/AJPH.2008.149005
PMCID: PMC2881664  PMID: 19443822
20.  Earlier age at menarche is associated with higher diabetes risk and cardiometabolic disease risk factors in Brazilian adults: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) 
Objectives
Early menarche has been linked to higher risk of type 2 diabetes in Western and Asian societies, yet whether age at menarche is associated with diabetes in Latin America, where puberty and diabetes may have different life courses, is unknown. We tested the hypothesis that earlier menarche is associated with higher diabetes risk in Brazilian adults.
Methods
We used data from 8,075 women aged 35-74 years in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who had complete information on age at menarche, diabetes status, and covariates. Diabetes was defined based on self-reported physician diagnosis, medication use, and laboratory variables (fasting glucose, 2-hour glucose, and glycated hemoglobin). Poisson regression was used to generate risk ratios (RR) and 95% confidence intervals (CI).
Results
Menarche onset < 11 years [vs. 13-14 years (referent)] was associated with higher risk of diabetes (RR = 1.34; 95% CI: 1.14-1.57) after adjusting for sociodemographic factors, maternal education, maternal and paternal diabetes, and birth weight. This persisted after further control for BMI at age 20 years and relative leg length. Additionally, among those not taking diabetes medications, earlier menarche [<11 years vs. 13-14 years (referent)] was associated with higher % glycated hemoglobin (p < 0.001), alanine aminotransferase (p < 0.001), triglycerides (p < 0.001), C-reactive protein (p = 0.003), waist circumference (p < 0.001), and BMI measured at baseline exam (p < 0.001).
Conclusion
These findings support the hypothesis that earlier menarche is associated with greater risk for adult diabetes and cardiometabolic disease in the Brazilian context.
doi:10.1186/1475-2840-13-22
PMCID: PMC3899384  PMID: 24438044
Puberty; Menarche; Diabetes; Cardiometabolic risk; Metabolic syndrome; Obesity; Brazil; Nutrition transition; Primordial prevention; Epidemiology
21.  Age at Menarche and Risks of All-Cause and Cardiovascular Death: A Systematic Review and Meta-Analysis 
American Journal of Epidemiology  2014;180(1):29-40.
We conducted a systematic review and meta-analysis to investigate the associations between menarcheal age and all-cause and cardiovascular death. Medline, Embase, Scopus, and Web of Knowledge were searched for articles published prior to March 2013 reporting on the associations between menarcheal age and death from all causes or from cardiovascular disease (total cardiovascular disease, ischemic heart disease (IHD), and stroke) in adult women. Nine articles were eligible for inclusion; these reported 5 estimates each for death from all causes and total cardiovascular death, 6 estimates for IHD, and 7 estimates for death from stroke. Our meta-analysis showed that each 1-year increase in age at menarche was associated with a 3% lower relative risk of death from all causes (pooled hazard ratio = 0.97, 95% confidence interval: 0.96, 0.98) with low heterogeneity (I2 = 32.2%). Meta-analysis of 2 cohorts showed a higher risk of death from all causes for women who experienced early menarche (at <12 years of age) versus “not early” menarche (at ≥12 years of age) (pooled hazard ratio = 1.23, 95% confidence interval: 1.10, 1.38; I2 = 0%). An inverse association between age at menarche and death from IHD was observed only among nonsmoking populations or populations with low prevalence of smoking. We found no evidence of association between age at menarche and death from all cardiovascular diseases or stroke. Early menarche was consistently associated with higher risk of death from all causes. Further studies are needed to clarify the role of menarcheal age on cardiovascular outcomes and to investigate the potential modifying role of smoking.
doi:10.1093/aje/kwu113
PMCID: PMC4070937  PMID: 24920784
cardiovascular disease; death rate; menarche; mortality; puberty
22.  Association of Age at Menarche and Menstrual Characteristics with Adult Onset Asthma among Reproductive Age Women 
Background
Observations of increasing asthma incidence, decreasing age at menarche, and common risk factors have led investigators to hypothesize potential associations of age at menarche or menstrual characteristics with incidence of adult onset asthma. We evaluated these associations among reproductive age women.
Methods
Study participants were selected from among women enrolled in a pregnancy cohort study. Information on age at menarche, menstrual characteristics, and history of asthma was collected using interviewer-administered questionnaires. Adult onset asthma was defined as asthma first diagnosed after onset of menarche. Women who had no information on asthma and menstrual history and those who were diagnosed with asthma before menarche were excluded. A total of 3,461 women comprised the analytic population. Logistic regression was used to estimate adjusted relative risk (aRR) and 95% confidence intervals (95% CI) relating age at menarche and menstrual characteristics with adult onset asthma.
Results
Mean age at menarche was 12.8 years (standard deviation=1.46). Among study participants, 7.5% were diagnosed with asthma after the onset of menarche. After controlling for potential confounders (age, race, body mass index, and socio-economic status), women who had early menarche (<12 years old) had 60% higher risk of being diagnosed with adult onset asthma as compared with women who did not have early menarche (≥ 12 years old) (aRR= 1.59, 95% CI 1.19 – 2.13). Menstrual irregularities or abnormal (short or long) cycle length were not associated with risk of adult onset asthma. In addition, no significant interaction was observed between age at menarche or menstrual characteristics with body mass index or physical activity (in adolescence) in relation to adult onset asthma.
Conclusion
Early menarche is associated with a higher risk of developing adult onset asthma among reproductive age women. Mechanisms for this association are potential areas of future research.
doi:10.4172/2161-038X.1000111
PMCID: PMC4192656  PMID: 25309820
23.  Lower age at menarche affects survival in older Australian women: results from the Australian Longitudinal Study of Ageing 
BMC Public Health  2010;10:341.
Background
While menarche indicates the beginning of a woman's reproductive life, relatively little is known about the association between age at menarche and subsequent morbidity and mortality. We aimed to examine the effect of lower age at menarche on all-cause mortality in older Australian women over 15 years of follow-up.
Methods
Data were drawn from the Australian Longitudinal Study of Ageing (n = 1,031 women aged 65-103 years). We estimated the hazard ratio (HR) associated with lower age at menarche using Cox proportional hazards models, and adjusted for a broad range of reproductive, demographic, health and lifestyle covariates.
Results
During the follow-up period, 673 women (65%) died (average 7.3 years (SD 4.1) of follow-up for decedents). Women with menses onset < 12 years of age (10.7%; n = 106) had an increased hazard of death over the follow-up period (adjusted HR 1.28; 95%CI 0.99-1.65) compared with women who began menstruating aged ≥ 12 years (89.3%; n = 883). However, when age at menarche was considered as a continuous variable, the adjusted HRs associated with the linear and quadratic terms for age at menarche were not statistically significant at a 5% level of significance (linear HR 0.76; 95%CI 0.56 - 1.04; quadratic HR 1.01; 95%CI 1.00-1.02).
Conclusion
Women with lower age at menarche may have reduced survival into old age. These results lend support to the known associations between earlier menarche and risk of metabolic disease in early adulthood. Strategies to minimise earlier menarche, such as promoting healthy weights and minimising family dysfunction during childhood, may also have positive longer-term effects on survival in later life.
doi:10.1186/1471-2458-10-341
PMCID: PMC2908577  PMID: 20546623
24.  Factors associated with early menarche: results from the French Health Behaviour in School-aged Children (HBSC) study 
BMC Public Health  2010;10:175.
Background
Puberty is a transition period making physiological development a challenge adolescents have to face. Early pubertal development could be associated with higher risks of poor health. Our objective was to examine risk behaviours, physical and psychological determinants associated with early menarche (<11 years).
Methods
Early menarche was assessed in the Health Behaviour in School-aged Children French cross-sectional survey. Data were collected in 2006 by anonymous self-reported standardized questionnaire from a nationally representative sample of 1072 15 years old girls in school classrooms. Family environment, school experience, physical and psychological factors, risk behaviours (substance use and sexual initiation) were recorded. Logistic regression models were applied (analysing for crude and adjusted relationships between early menarche and risk behaviours controlled for family context).
Results
Median age at menarche was 13.0 years; 57 girls (5.3%) were early-matured. Controlled for familial environment, early menarche was associated with having had more than two life-drunkenness episodes (adjusted OR = 2.5 [1.3-4.6]), early sexual initiation (adjusted OR = 2.8 [1.3-6.0]) and overweight (adjusted OR = 7.3 [3.6-14.9]).
Conclusion
Early-maturing girls may affiliate with older adolescents, hence engage in risk behaviours linked to their appearance rather than their maturity level. Factors associated with early menarche highlight the need to focus attention on early-matured girls to prevent further health problems linked to risk behaviours.
doi:10.1186/1471-2458-10-175
PMCID: PMC2853511  PMID: 20353570
25.  Association of maternal and intrauterine characteristics with age at menarche in a multiethnic population in Hawaii 
Cancer causes & control : CCC  2009;21(2):259-268.
This study seeks to further elucidate the mother–daughter hormonal relationship and its effects on daughter’s breast cancer risk through the association with early age at menarche. Four hundred and thirty-eight healthy girls, age 9–18 and of White, Asian, and/or Polynesian race/ethnicity, were recruited from an HMO on Oahu, Hawaii. Anthropometric measures were taken at a clinic visit, and family background questionnaires were completed. Cox proportional hazards regression was used to test the association of maternal and intrauterine hormone-related exposures with age at menarche. Weight and gestational age at birth and maternal pregnancy-induced nausea were not associated with age at menarche. Each year older of the mother’s age at menarche was associated with a 21% reduced risk of an early age at menarche for the daughter (95% CI: 0.73–0.86). This association between mother’s and daughter’s menarcheal age was statistically significant for girls of Asian, White, and Mixed, Asian/White race/ethnicity, but not for girls of Mixed, part-Polynesian race/ethnicity (pinteraction = 0.01). There was a suggestion that maternal history of breast cancer was associated with an increased risk of early age at menarche (HR = 2.18, 95% CI: 0.95–4.98); there was no association with second-degree family history. These findings support the hypothesis that maternal and intrauterine hormone-related exposures are associated with age at menarche.
doi:10.1007/s10552-009-9457-1
PMCID: PMC2811221  PMID: 19862633
Menarche; Breast cancer; Hormones; Mothers

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