Is variation between countries in age at menarche of girls explained by Body Mass Index? Candace Currie, Child and Adolescent Health Research Unit, University of Edinburgh; Dorothy Currie, Child and Adolescent Health Research Unit, University of Edinburgh, Saoirse Nic Gabhainn, Health Promotion Research Centre, National University of Ireland, Galway, Emmanuelle Godeau, Service médical du rectorat and INSERM U558 - Université paul Sabatier, Toulouse Namanjeet Ahluwalia, INSERM U558, University Paul Sabatier, Toulouse, France

Early age of menarche: a public health concern Age at menarche (AAM) has been declining across recent decades in North America and Europe This is of public health concern since early menarche is associated with range of negative health consequences including risk behaviour and mental health Causal factors in age at menarche are wide ranging and complex It has been hypothesised that declining age at menarche is associated with rising levels of overweight and obesity

Evidence for decline in age of menarche Declining AAM over recent decades has been documented in a number of countries including: USA (Herman-Giddens, 2007) Canada (Harris et al, 2008) Ireland (O’Connell et al, 2008) Various European countries (de Muinck Keizer- Schrama and Mul, 2001; Ong et al, 2006)

Evidence for decline in AAM In US difference of 12 months in AAM in pre-1920s cohort compared to cohort More recent US data shows decline of 2.3 months between 1988/94 and 1999/2002 In Canada almost 9 month decline in AAM between cohorts born before 1933 and those born in In Europe AAM in Netherlands has declined by 7 months in 4 decades ( ) In general there is a general lack of comparable data across time and across countries

Evidence that weight in childhood predicts early menarche there is a convincing body of evidence that weight in early childhood strongly predicts age at menarche early menarche has also been linked to development of adult overweight but research suggests causal pathways are through the association between childhood weight and early AAM

Childhood weight, timing of menarche and adult weight Must et al (2005) prospective study in the US girls who were overweight before menarche were 8 times more likely to be overweight as adults early menarche (12 years or younger) did not elevate risk of adult overweight The influence of early AAM on adult female weight was due to effect of childhood overweight on early maturation

Childhood weight predicts timing of menarche Lee et al (2008) longitudinal study height and weight measurements at 36 and 54 months, and grades 1, 4, 5 and 6 with pubertal assessments in grades showed: relatively high BMI at age 3 and rate of change of BMI between age 3 and grade 1 associated with earlier onset of puberty

Childhood weight predicts timing of menarche Freedman et al (2003) longitudinal Bogaluso heart study in USA relatively fat 9 year old girls tend to undergo menarche earlier than thinner girls each standard deviation increase in pre-menarcheal BMI approximately doubles odds of early AAM (12 years or younger) most of the influence of menarcheal age on obesity was due to the association of childhood obesity to menarcheal age and adult obesity

Childhood weight predicts timing of menarche Ong et a l (2009) rapid weight gain between 1 and 2 months and also between 2 and 9 months associated with increased body fat relative to lean mass at age 10 and also with earlier menarche. Tam et al (2006) higher weight mass at age 8 predicted earlier age at menarche in a cohort study of 156 girls followed from birth. being long and light at birth also predicted earlier menarche. combining these measures best predicted age at menarche

Concurrent population increase in BMI and decline in AAM Anderson et al (2003) analysed 2 nationally representative samples in US, one from early 1990s and one from 25 years earlier found a drop of about 2.5 months in average age of menarche between periods 1963–1970 and 1988–1994 concurrent upward shift in population body mass index

Model of relationship between body weight and menarche Birth weight Childhood weight/ rate of growth in childhood Age at menarche Adult weight

Cross-national variation in AAM Few studies have compared age at menarche in different countries Parent et al (2003) reviewed existing evidence and found significant variation between countries evidence stems from multiple sources from different population groups and studies using different methodologies general lack of comparable data across time within individual countries, or across different countries

Copyright ©2003 The Endocrine Society Parent, A.-S. et al. Endocr Rev 2003; 24: FIG. 2. Average (mean or median) ages at onset of breast development (B2) or menarche in different well-off populations around the world USA EUROPE Other countries worldwide

Cross-nationally comparable data on AAM & BMI such data is gathered in the Health Behaviour in School-Aged Children: WHO Collaborative Cross-National Study (HBSC) allows us to examine whether variation in AAM between countries is associated with BMI

HBSC Study 43 member countries in Europe and North America cross-sectional school-based self-complete surveys conducted every four years survey instrument is an internationally standardised self- report questionnaire administered in a school class period representative samples of approximately 1550 pupils in three age groups - 11,13 and 15 years data presented is from 2005/2006 (hereafter ‘2006’) and 2001/2002 (hereafter ‘2002’) surveys

Health Behaviour in School-Aged Children: WHO Collaborative Cross-National Study (HBSC) cross-sectional internationally comparable data on age at menarche (AAM) and body mass index (BMI) is used from 34 countries that participated in 2006 study across Europe and North America participants were ~ 27, year old girls from nationally representative random samples of schools country level data on BMI was used from 29 of these countries that also participated on 2002 international study

Measures and sample size Menarcheal status and AAM obtained from two part question that asks if menstruation had begun and age in year and months of first menstruation each pupil designated as pre- or post-menarcheal (after cleaning to remove those who give no information on month at menarche or age below 5 years or above current age)

Sample size Sample total of 7468 girls were excluded from analysis through cleaning for multi-level modelling only 29 countries (which also included 2002 data) were included reducing sample size to 16,000

Measures BMI BMI (kg/m 2 ) was calculated from self-reported height and weight without clothes or shoes girls categorised as ‘overweight/obese’ or ‘normal/underweight’ using international standardised age- and sex- specific metric proposed by Cole et al (2000)

Statistical analysis Median age at menarche and 95% confidence intervals was calculated using Kaplan–Meier estimation (survival analysis) Univariate regression was used at country level to measure association between prevalence of overweight and median AAM When AAM was outcome variable in regression models age at menarche was imputed as current age for those who were pre-menarcheal

Statistical analysis the proportion of 11-year olds in each country that were overweight/obese in 2002 was used as country level indicator of BMI 11 year olds in 2002 are same cohort as 15 year olds in 2006 (this provides non-contemporaneous data on BMI in each country and data from an age-group when fewer pupils, only 17%, have reached menarche)

Median AAM across countries 12 months range in median AAM among 15 year olds in 2006: ranging from 12 y/ 5m in Italy to 13y/ 5 m in Latvia youngest median AAM reported in Mediterranean, western European and North American countries oldest median AAM mainly in eastern European countries, Flemish Belgium and Israel

Variation in overweight across countries prevalence of overweight (including obese) also varied substantially across countries ranged from 4% in Romania to 28% in Malta among 15 year olds in 2006 ranged from 4% in Estonia to 21% in the USA among 11 year olds in 2002

Proportion of overweight 15 year old girls by country (2006 survey)

Association between median AAM and proportion overweight 15 year old girls Individual level At an individual level within and across countries a significant association was found between AAM and overweight Country level regression analysis of AAM and overweight conducted on 34 countries on 2006 data among 15 year olds shows an association of r 2 =23.7%

Association between prevalence of overweight 15yo girls and median AAM in each country Higher prevalence of overweight at country level associated with lower median AAM  = (0.072) r 2 =23.7%

Country level analysis using 2002 data from 11 year olds regression analysis conducted on data from 29 countries using 11 year old girls BMI data from 2002 and 15 year old girls AAM data from 2006 shows an association between prevalence of overweight among 11 year olds girls in each country in 2002 and median AAM among 15 year old girls in same country in 2006 (r 2 =29.8%).

Association between prevalence of overweight 11yo girls (2002) and median AAM, 15 yo girls (2006)  = (0.094) r 2 =29.8%

Next stage of analysis: Multilevel Modelling of variation in AAM Country level variation in AAM was estimated using 4- level hierarchical regression models, with age at menarche as the outcome variable Levels: Individual School Strata (eg geographic region) Country

Multi-level modelling Outcome – age at menarche Model 1 -Null model – Estimate country level variance in age at menarche (100%) Adjust for age and socioeconomic status (family affluence) Model 2- Add in individual level BMI Model 3 – Add in country level prevalence of overweight 11 year olds in 2002

Multilevel models of age at menarche (months)

Conclusions There is significant variation in AAM across countries There is significant variation in prevalence of overweight across countries There is a significant association between overweight and AAM at the individual level 40% of country level variation in AAM is explained by BMI

Implications over and above individual BMI there appears to be country level influence of prevalence of overweight on AAM this needs further investigation… as levels of overweight increase in populations across Europe then AAM in these countries may decline

Critique and limitations data on age at menarche and height and weight are self- reported self report weight – tends to be slightly underestimated and unlikely to affect general findings missing data on height and weight varied between countries: 12% to 57%; missing data likely to be from heavier individuals self reported age at menarche is robust measure -cross checked against clinical/ maternal reports missing data on AAM – country average 5.5%

Future work new data being collected in 2009/2010 in 43 countries will allow analysis to be repeated longitudinal research in context of HBSC would be useful – some countries are doing this assess public health significance of findings for prevention of overweight in population – environmental approach versus individual approach

Additional slides

Proportion of overweight/obese 11 year old girls by country (2002 survey)

Association between overweight/obesity in two cohorts There is a strong association between the proportion of overweight/ obese girls aged 11 in 2002 and an independent cohort of 15 year olds surveyed in the same countries in 2006 This provides a validity check on BMI data

Regression between proportions of overweight/obese girls aged 11 (2002) and girls aged 15 (2006) r 2 =0.472

Missing BMI data Range in 34 countries: 12% to 57% 10 countries >10% 6 countries > 15% 4 countries > 50%