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; candace.currie@ed.ac.ukDorothy 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, ToulouseNamanjeet 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 1980-84 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 1986-1990

• In Europe AAM in Netherlands has declined by 7 months in 4 decades (1955-1997)

• 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 4 - 6

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

Childhoodweight/ 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; 24:668-693

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 countriesworldwide

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 ~ 27,000 15 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 sizeMenarcheal 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

MeasuresBMI

• BMI (kg/m2) 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)

0.0%

5.0%

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MT

US GL

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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 r2=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

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0% 5% 10% 15% 20% 25% 30%

Prevalence of overweight 15yo girls

Med

ian

ag

e at

men

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ths)

= -0.24 (0.072) r2=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 (r2=29.8%).

Association between prevalence of overweight 11yo girls (2002) and median AAM, 15 yo girls (2006)

148

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0% 5% 10% 15% 20% 25%

Prevalence of overweight 11 year old girls

Med

ian

ag

e at

men

arch

e (m

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ths)

= -0.331 (0.094) r2=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)

Null model Model 2 individual BMI

Model 3 Country overweight

Fixed effects Individual level

Family Affluence 0.75 (0.48 to 1.02) 0.53 (0.26 to 0.80) 0.54 (0.27 to 0.81)

Age (months, centered) 0.06 (0.00 to 0.12) 0.09 (0.03 to 0.14) 0.09 (0.03 to 0.14)

BMI (centered) - -1.02 (-1.09 to -0.95) 1.01 (-1.09 to -0.94)

Country Level

Prevalence of overweight (age 11, 2002)

- - -0.25 (-0.43 to -0.08)

Random effects

Country level variance (se)

6.32 (2.05)

4.83 (1.64)

3.53 (1.28)

100% 80% 59%

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)

Prevalence of overweight/obese 11yo girls by country, 2002 HBSC study

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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)

0%

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Proportion overweight at age 11

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r2=0.472

Missing BMI data

• Range in 34 countries: 12% to 57%

• 10 countries >10%

• 6 countries > 15%

• 4 countries > 50%