Age at Menarche and Its Association with Excess Weight and Body Fat Percentage in Girls in the Southwestern Region of the Brazilian Amazon

Accepted Manuscript Age at Menarche and its Association with Excess Weight and Body Fat Percentage in Girls in the Southwestern region of the Brazilian Amazon Ivanice Fernandes Barcellos Gemelli, MSc, Edson dos Santos Farias, PhD, Orivaldo Florêncio Souza, PhD PII:

S1083-3188(16)00186-8

DOI:

10.1016/j.jpag.2016.02.011

Reference:

PEDADO 1971

To appear in:

Journal of Pediatric and Adolescent Gynecology

Received Date: 20 September 2015 Revised Date:

18 February 2016

Accepted Date: 22 February 2016

Please cite this article as: Gemelli IFB, Farias EdS, Souza OF, Age at Menarche and its Association with Excess Weight and Body Fat Percentage in Girls in the Southwestern region of the Brazilian Amazon, Journal of Pediatric and Adolescent Gynecology (2016), doi: 10.1016/j.jpag.2016.02.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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ACCEPTED MANUSCRIPT Original Study

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Age at Menarche and its Association with Excess Weight and Body Fat Percentage

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in Girls in the Southwestern region of the Brazilian Amazon

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Ivanice Fernandes Barcellos Gemelli, MSc1; Edson dos Santos Farias, PhD1; Orivaldo

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Florêncio Souza, PhD2

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Department of Health Sciences, Federal University of Rondônia, Brazil

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Department of Health Sciences, Federal University of Acre, Brazil

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Requests for reprints and galley proofs

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Ivanice Fernandes Barcellos Gemelli

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Universidade Federal de Rondônia - UNIR

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Campus - BR 364, Km 9,5

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76.801-059 - Porto Velho – RO, Brazil

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Telefax: +55 69 3224-2626

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E-mail: [email protected]

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Corresponding author

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Ivanice Fernandes Barcellos Gemelli

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Universidade Federal de Rondônia - UNIR

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Campus - BR 364, Km 9,5

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76.801-059 - Porto Velho – RO, Brazil

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Telefax: +55 69 3224-2626

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E-mail: [email protected]

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Source of Funding: This project was funded by The Federal University of Rondônia -

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Research Initiative Grant.

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Conflicts of Interest: None of the authors have any conflicts of interest.

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ACCEPTED MANUSCRIPT 1

Abstract

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Study objective: Analyze age at menarche and its association with excess weight and

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body fat percentage.

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Design: School-based cross-sectional survey.

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Setting: Southwestern region of the Brazilian Amazon.

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Participants: The sample was made up of 727 girls, in the 8- to 16-year age range,

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divided into three groups: early, normal and late menarche, from public and private

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schools, selected through proportional stratified random sampling.

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Intervention: Bioimpedance was used to measure body fat percentage and body mass

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index, applying the Global School-Based Student Health Survey questionnaire to

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categorize behavior variables. Age at menarche was determined by the status quo

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method. Sexual maturity was assessed through self-assessment according to criteria

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described by Tanner.

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Results: Overall age at menarche was 11.52 (±1.35), early 10.48 (±0.78), normal 12.39

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(±0.50) and late 14.27 (±0.51). Prevalence of excess weight and body fat was 28.1%

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and 40.1%, among those with menarche. There was a positive association between

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excess weight and body fat with age at early menarche (p=0.000 and 0.015).

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Conclusions: Age at menarche among girls from the Amazon region is similar to that of

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industrialized countries. Prevalence of excess weight and body fat was high, and there

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was evidence of an association between age with early menarche and excess weight.

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Trends in age at menarche and stage of sexual maturation should be monitored with

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related factors, in order to adopt obesity control strategies from an early age.

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Keywords: Menarche; Puberty; Obesity; Adolescent.

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Introduction

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Puberty is a biological phenomenon, in which morphological and physiological

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changes occur as a result of the activation of neural and hormonal mechanisms on the

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hypothalamic–pituitary–adrenal/gonadal (HPG) axis, secondary sexual characteristics

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begin to develop and the potential for sexual reproduction is reached, with the menarche

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being identified as a marker for reproductive maturity; however, this does not occur

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simultaneously with psychosocial maturity.1

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Genetic factors, of which the gene CYP3A4 (metabolizes testosterone), the LEP

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gene, a leptin gene variant, Xbal and Pvull polymorphisms of the estrogen receptor

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alpha gene, as well as polymorphism in ESR1 which codifies an estrogen receptor and

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is essential for sexual development and reproductive function, are related to age at

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menarche1 and determine the onset of puberty; however, other factors seem to have an

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influence, among them being nutritional status, general health, psychological status, and

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environmental factors.2

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Early puberty may cause adverse effects and consequences to health, influenced by intrinsic and extrinsic factors, which are of interest for public health.3

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Age at the onset of pubertal maturation and menarche is occurring earlier in the

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USA, in the last 50 years and the causes of this change have been studied.4 Although

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there is a more modest decrease in age at menarche in relation to breast development,

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this suggests that in addition to similar factors there are also singular factors that are

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individually associated to breast development and menarche.5

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Age at menarche seems to continue to decline in developed and developing

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countries; however, this fall does not occur in the same manner due to different

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influences from climatic, ethnic6 and nutritional factors.7-8

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A meta-analysis study, a European ancestry cohort, found a close link between the

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genetic regulation of energy homeostasis and pubertal timing, suggesting the presence

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of other pathways for this regulation, and identifying mean age of menarche as 12.4 to

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13.6 years.1

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Studies in several countries have found that the overall mean age at menarche ranges

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from 12.4 to 13.6 years.9-10

The rising global prevalence of obesity raises questions on to what extent excess

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weight may influence age of menarche. Obesity has been recognized as the major

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epidemic of the 21st century. Worldwide, 20% of children are affected by excess weight,

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and estimates point to a growth of approximately 15 million children and adolescents

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with excess weight.11

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Some factors may influence excess weight, such as physical activity, an important

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factor to maintain increased levels of basal metabolic rate, and amongst those that do

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not depend on external influence are genetic factors, and people who have a gene

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associated with obesity, termed the fat mass and obesity-associated (FTO) gene, have

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70% greater chance of becoming overweight, and weigh three kilograms more than

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people who do not have a copy.12

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In addition to these, the ghrelin hormone factor, neuropeptide Y (NPY) and

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hypothalamic agouti-related protein (AGRP) reduce metabolism and promote

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adipogenesis. Regarding prevalence in adolescents, studies in Brazil report that the

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prevalence of excess weight (overweight and obesity) is approximately 13.3%, being

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9.5% for overweight and 3.5% for obesity,13 whereas a more recent study found excess

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weight as 19.3 to 25.8%.14 Yet a European study points to a prevalence of excess weight

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of 17.9 to 33.4%.15

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ACCEPTED MANUSCRIPT In three longitudinal studies16-18, the first with 354 girls conducted by the National

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Institute of Child Health and Human Development Study of Early Child Care and Youth

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Development, showed that a higher body mass index (BMI) z-score in girls as young as

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36 months of age is associated to early puberty, which suggests that increasing rates of

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obesity in the United States may result in an earlier mean age for the onset of puberty in

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North American girls. The second showed that “among early-menarcheal African

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Americans, 57.5% had a BMI greater than the 85th percentile, and 32.5% had a BMI

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greater than the 95th percentile”, and the third demonstrated that increased weight seems

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to be a consequence, and not a determinant for age of menarche, and the shifts in BMI

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and mean age at menarche may be independent events; it also showed that girls with

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menarche before 11.9 years present cardiovascular risk factors, such as high blood

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pressure and glucose intolerance, independent of BMI.

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In Brazil, in the last decade, there has also been a change in obesity rates; in the

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Amazon region data is not available on the relationship between the rates of excess

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weight and age at menarche.

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In light of this, the objective of this study was to analyze age at menarche and its

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association with excess weight and body fat percentage in adolescent school girls in the

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Brazilian Amazon region.

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Materials and Methods

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This was a school-based, descriptive and cross-sectional study conducted in the city

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of Porto Velho, in the state of Rondônia, with 428,527 inhabitants, located in the

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southwest region of the Brazilian Amazon. The estimated total population of enrolled

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ACCEPTED MANUSCRIPT students, attending primary and secondary schools in Porto Velho was 26,546 students

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distributed in the 8- to 16-year age range. This study was conducted during the months

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of November and December 2014, data was collected in cooperation with the State

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Secretariat of Education (Rondônia). The schools were stratified according to the

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number of students using the simple randomization technique of pairing-proportionality

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with students from public, 479 (44.48%) and private schools, 598 (55.52%).

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The equation, no = 1 / Eo² n = N . n / N + no,19 was used to calculate our sample size

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based on a prevalence of 50% for excess weight, 3% margin of error, 95% confidence

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interval, which provided a total of 1026, accounting for a 5% non-response rate the

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study was conducted with 975 participants. After data collection for analysis, only girls

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with menarche (divided into three groups: early, normal and late) were included in the

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study, 248 girls that did not report the event (menarche) were excluded, resulting in 727

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individuals, with a 74.6% response rate.

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The selection process was conducted in three stages: first a stratified sample

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proportionate to the number of schools in each stratum (north, south, east and west

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areas) of the city was made; the second stage was the selection schools from each

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stratum through a proportional random selection in each stratum; and, in the third stage

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the classes were randomly selected, from which all female students were selected to

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participate in the study. This sampling process ensured that each student had the same

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chance of being selected. Inclusion criteria - all students were volunteers, with

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menarche, whose parents signed the informed consent form and agreed to participate in

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this two-stage study: stage 1) completing the questionnaire; and stage 2) having

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anthropometric measurements taken (body weight, height) and bioimpedance analysis

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(body fat % (BF%), body fat, muscle mass and BMI).

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ACCEPTED MANUSCRIPT Two questionnaires were used: 1) Associação Brasileira de Empresas de Pesquisa /

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Brazilian Market Research Association (ABEP), Brazilian Economic Classification

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Criteria. Available at: http://www.abep.org.br/mural/anep/04-12-97-cceb.htm. Accessed

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in February 2015, for socio-economic classification purposes, which takes into account

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the number of household appliances in general, classifying individuals according to

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social class - A (upper class), B (upper middle class), C ( middle class) and D (lower

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class); and 2) Global School-Based Student Health Survey (GSHS), self-administered,

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proposed by the World Health Organization (WHO), available for consultation on the

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Internet (http://www.who.int/chp/gshs/en). The questionnaire addresses ten key topics:

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(1) Alcohol use, (2) Dietary behaviors, (3) Drug use, (4) Hygiene, (5) Mental health, (6)

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Physical activity, (7) Protective factors, (8) Sexual behaviors, (9) Tobacco use, and (10)

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Violence and unintentional injury.

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The procedure for completion of the questionnaire was - in the classroom, in the

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presence of the researchers, and the teacher who helped them. The questionnaire was

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read and explained by the interviewer, and, while it was being filled in, doubts were

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cleared. When the questionnaires were completed, they were collected for analysis. The

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questions on the questionnaire were all closed with a single answer choice.

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The independent variables were social class (A, B, C and D), Living with parents

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(parents = mother and father, others (blood and non-blood relatives), Physical activity

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(active = individuals who reported participating in at least 30 minutes of moderate or

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vigorous physical activity, on three or more days a week; inactive = all others),

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Watching television (less or equal to two hours daily and more than two hours in front

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of the television).

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Mean age at menarche was determined using the status quo method by questioning

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the girl if she had or not had her first menstruation. For positive responses, a

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ACCEPTED MANUSCRIPT retrospective questionnaire was used seeking to identify the day, month and year of the

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event. Stage of sexual maturity was assessed through self-assessment with comparison

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to pictures of the five breast development classification stages (B1-B5), according to

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criteria described by Marshall & Tanner (1969).20 Girls with menarche with Tanner

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stage B2 or above with menstruation were considered, age at menarche was calculated

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subtracting the date of birth from the date at which first menarche has occurred,

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adopting the following cutoff points for age at menarche: early menarche (≤ 11 years),

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normal menarche (12 and 13 years) and late menarche (≥ 14 years).4

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Height was measured using a portable stadiometer according to protocol

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recommended by Petroski (2009),21 and body weight, BF%, muscle mass, body fat

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mass, and BMI using a bioimpedance device, for such measures a tetrapolar

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bioelectrical impedance analyzer (InBody, Rio de Janeiro) was used. This device

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measures the electrical resistance applied to the body, through predetermined electrodes

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on the soles of the feet and hands. The participant was asked not to eat anything for 2

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hours or do physical activity before the test, not to be menstruating and remain only

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with the physical education clothing, removing shoes, socks and metal objects.

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Technique: standing position on the platform, with minimal clothing, with feet parallel

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to each other, between which flows a minimum electric current that measures the body's

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resistance to current flow, according to protocol recommended by the National Institutes

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of Health (1996).22 The team was previously trained to apply the questionnaire and take

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measurements, which was made up of a physician-researcher and medical school

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students, all work was conducted in the school environment.

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Classification of nutritional status of the schoolchildren, according to BMI, was

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based on criteria proposed by the Center for Health Statistics in collaboration with the

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National Center for Chronic Disease Prevention and Health Promotion (CDC).23 The

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cutoff points adopted were: without excess weight (> -2 and < +1 z-score), with excess

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weight (≥ +1 z-score); and the cutoff points for the classification of BF%, according to

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recommendations proposed by Slaughter et al.,24 which adopts ≥ 30 with risk of excess

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body fat, and < 30 without risk of excess body fat. In the descriptive analysis, absolute frequency measurements were made for all

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variables analyzed according to age at menarche (early, normal and late) using Pearson's

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chi-square test, with the significance level α = 0.05. Binary multiple logistic regression

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was also performed to investigate the association between BMI z-score categories (with

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and without overweight) and fat % (with and without fat) with age at menarche (early,

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normal and late), adjusted for the following covariates: socioeconomic status, living

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with parents, number of siblings, physical activity, television viewing and maturity

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stages. The values of odds ratios and the 95% confidence interval (95% CI) were

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obtained using multiple binary logistic regressions. P values less than 0.05 were

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considered statistically significant. Calibration was calculated using the Hosmer-

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Lemeshow test and the P value >0.05 indicates that the model fits the data. All

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statistical analyses were performed using the statistical software package SPSS, version

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17.0.

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The study was approved by the Research Ethics Committee of the Federal University

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of Rondônia on 07/16/2014, CAAE: 335422014.0.0000.5300. Regulatory norms for

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research involving human beings were followed according to resolution number

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466/2012, certified by the National Health Council on December 12, 2012.

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Results

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ACCEPTED MANUSCRIPT Data from 727 schoolgirls with menarche in the in the 10- to 18-year age range were

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analyzed, mean age at menarche was 11.52±1.35 (8.0 – 16.0) years. The mean age of

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the girls that did not report menarche (n=350) was 11.12±0.93 (9.08 – 14.10) years,

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excluded since they do not meet the proposed objective of the study, to analyze girls

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with and its association with excess weight.

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The prevalence of excess weight was 28.1%, corresponding to 260 girls, and excess

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body fat was 40.1%, or 371 girls from the sample with menarche. Regarding study

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variables, only watching television was associated (positively) with the classification of

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age at menarche. For menarche, the highest frequency of occurrence was at Tanner

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stage B4, of which 45.5% were classified as early, 56.4% as normal, and 49.0% as late.

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The prevalence of excess weight and body fat was greater in girls with early menarche

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age (35.5% and 48.9%) when compared to the others (Table 1)

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[Table 1]

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Figure 1 presents positive association for excess weight and body fat with early menarche age (p=0.000 and 0.015).

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[Figure 1]

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The association between age at menarche and excess weight according to BMI z-

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score showed statistical significance in the adjusted model (socio-economic levels,

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living with parents, number of siblings, physical activity, watching television, and

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maturity stage). The girls who presented normal or late menarche had less chance of

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having excess weight in relation to those with early menarche; however, no alteration

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was observed in the odds ratio between age at menarche, and excess weight after

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adjustment for socio-economic variables (Table 2).

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[Table 2]

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The association between excess body weight, and age at menarche remained

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significant in the non-adjusted model, and after adjustment, only in the model with the

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normal menarche group, presented less chance of having excess body fat in relation to

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the early menarche group. This association was not evident in the late menarche group (Table 3).

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[Table 3]

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The inclusion of blocks of adjustment variables minimally altered the odds ratio of normal and late menarche age in association with excess weight and body fat.

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Discussion

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Despite major changes in the nutritional profile of the worldwide and Brazilian

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populations, there are still few studies that address this theme in association with sexual

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maturity. Current studies, which investigate age at menarche, and possible changes in

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this mean age are necessary for us to be able to predict impact on public health, and

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repercussions on fertility in general.

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ACCEPTED MANUSCRIPT The present study found a high prevalence of early menarche (52.27%) , together

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with the fact that these presented The high prevalence of early menarche (52.27%),

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together with the fact that these girls presented high prevalence of excess weight

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(35.5%) and excess body fat (48.90%) when compared to girls with normal and late

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menarche. This suggests that there is a significant association between age at menarche

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and excess weight.

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In comparison with Tanner, 1969,20 who studied a group of British girls and found

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the mean age at menarche was 13.47±0.10; and as this study is from the 20th century it

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emphasized association between nutritional status and age at menarche. Since then, a

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decrease in age at menarche has been observed, as much in developed as in developing

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countries, and studies from around the world have sought to clarify the relationship

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between the shift in age at menarche and its possible driving factors, among them being

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genetics, environment, seasonality, nutritional status, and physical activity, with the

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menarche also being used as an indicator of socio-economic change since it suffers

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interference from the environment.1,25,26

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Carvalho et al.,8 in a review, identified that age at menarche in India in the year 2000

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was 13.6 years, and 12.8 years in the USA, thus demonstrating the differences in age

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with regards to social class; the same author reports that in 2006, age at menarche in the

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USA was 12.3 years (a reduction of 5 months in less than a decade), and in Demark, in

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2006, 13.4 years, the author attributed this difference to the low prevalence of obesity in

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this country in comparison to the USA.

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A study conducted in the southeast region of Brazil,27 comparing two cross-sectional

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cohorts identified that the age of menarche had been anticipated in 3.24 months between

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2001 and 2010, being 12.35 and 12.08, respectively, with an increase in obesity and a

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reduction of normal weight individuals (without excess weight and fat); however, not

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only excess weight influenced age at menarche, since girls that were overweight, normal

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weight and without excess fat also had an earlier period. Therefore, possibly, it is not

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just the increase in the prevalence of excess weight that is involved; there may also be

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other factors at work.5 Three studies performed in two cities in the southeast of Brazil, in 2012 and 2014

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found similar results, with mean age at menarche being between 12 and 12.2

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years.10,25,27 With regards to the prevalence of obesity, Castilho et al. (2012)27 identified

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that prevalence for overweight was 22.9%, and 10% for obesity, in 2010, which was

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also greater than that of 2001, being 21.2 and 5.4%, respectively. A study in the

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Brazilian northeast showed that the prevalence of excess weight in adolescents, was

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13.3% for overweight and 3.8% for obesity.13

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Comparing international and Brazilian studies with the results from this study, we

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observed that the north region, the Brazilian Amazon region, had not only an earlier age

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at menarche, but also the girls with menarche presented higher BF% and prevalence of

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excess weight. This fact may be related to excess weight at the time of menarche. It is

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worth pointing out that this was not the case in previous studies, which reported age at

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menarche and prevalence of excess weight of adolescent students in the Amazon region.

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Yet girls without excess weight and without excess body fat, in their majority,

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seemed to present timing of menarche as normal or late.

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In assessing the prevalence of excess weight according to BMI and excess body fat

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according to BF%, between the menarche groups, we observed that there was smaller

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variation of BF% between the groups (p<0.015) and according to BMI prevalence

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variation was greater (p<0.000), which may be attributed to lower precision in using

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BMI as an adiposity indicator, as mentioned by the Fels Longitudinal Study.18

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ACCEPTED MANUSCRIPT Since excess weight, currently affects, as much girls from the upper classes as those

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from the intermediate classes, it is not surprising that menarche occurs at the same age

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in both.10 In this study there were no statistically significant differences between age at

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menarche, and the different social classes. This may be due to nutritional changes,

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which took place in the last decade; however, after the application of logistic regression,

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we observed that the socio-economic level, maintained a correlation with excess weight

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and age at menarche in all the adjusted models, and with BF%, the correlation was only

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maintained in relation to normal menarche. However, all models after logistic

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regression presented inverse correlation, between BMI and age at menarche.

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In the literature, studies have also identified an inverse correlation, between BMI,

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excess weight and age at menarche, suggesting that obesity may be largely responsible

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for the shift in the onset of puberty.4,10,28

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Data from the Family Budget Surveys, 2012 (Pesquisa de Orçamentos Familiares

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(POF) de 2012) (www.tabnet.datasus.gov.br, accessed in July 2015), with regards to

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income ratio in Brazil in the different regions, displayed that between 2011 and 2012,

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there were differences in all of the regions; however, in comparing the north region to

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the southeast, this difference was 19.85 – 15.36 and 21.50 – 13.52, respectively,

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showing a reduction in the north region, where economical abysm no longer exists,

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though with less impact, compared to the other more developed regions of Brazil.

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Nonetheless, our result points to age at menarche being lower in the north region than in

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the others, presupposing an approximation of social classes, with better nutrition

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accompanied by excess weight, as observed in this study.

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Assessing the differences between regions, age at menarche was anticipated in 2.7

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months in the southeast region of Brazil in a decade, and it has remained stable at 12.1

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years. When comparing the north of the country, data from this study, mean age at

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menarche was 11.52 years, 5.8 months earlier than in the Southeast.26 Inasmuch as the

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results from this study show an earlier age at menarche and an elevated prevalence of

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excess weight, in relation to the other Brazilian states, the repercussion of these findings

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is worrying. The outcomes of early age at menarche and association with excess weight is an

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issue that brings about health concern worldwide, the Fels Longitudinal Study18

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conducted in the 20th century, found that girls with less than 11.9 years at menarche

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presented cardiovascular risk factors, such as high blood pressure and glycose

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intolerance,29 independent of BMI. Regarding the fertility of girls with excess weight,

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they present earlier sexual maturation, and as a result they are exposed to sexual

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initiation earlier; and according to a Brazilian study, there is an increase in the number

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of pregnant adolescents, which is not the case in other western countries, and factors

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such as a global reduction in mean age at menarche, and the first sexual relationship are

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included in the risk context for the increase in these rates.30

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On the other hand, there is a worldwide reduction in the fertility rate, with 2.1

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children per female being necessary for population replacement, in Brazil this rate is

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1.94, being lower in the southeast at 1.75 and higher in the north region at 2.51, this

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may be due to less favorable socio-economic indicators, and also a higher proportion of

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rural population.31

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In addition to this, Brazil is an aging country, while the elderly population, aged 65

21

years or more will increase at an accelerated rate (2 to 4% a year), and the younger

22

population will reduce in the near future.32

23

Obesity and subfertility seem to be related, at least partially, a reduction in the

24

frequency of ovulation and increase in body weight seem to be an activity regulator of

25

the HPG axis. The hormones derived from adipose tissue influence fertility with leptin

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ACCEPTED MANUSCRIPT being among the possible regulators for the onset of puberty and reproductive capacity,

2

in addition to the effect of sex steroids accumulated in the fatty cells interfering on the

3

HPG axis.26,33 The adolescents in this study, in agreement with the literature, presented

4

early menarche associated to excess weight and this combined with increased longevity,

5

means that they will be exposed to a hormonal environment and sex steroids for a

6

longer period of time, and this may possibly lead to insulin resistance, increase in

7

cardiovascular diseases, and greater risk of breast cancer.4

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At the time of data collection, the girls who had already had menarche were between

9

Tanner stages B3 and B5, concurring with the first studies of sexual maturation stages,

10

or Tanner stages,20 in which the menarche usually occurs between Tanner stages B3 and

11

B4 (Table 1).

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Regarding sedentary behavior and age at menarche for the late menarche group, we

13

identified a significant association using the chi-square test (p<0.005) for watching

14

television at least 2 hours a day. After using physical activity and watching television as

15

adjustments, the multiple logistic regression confirmed association for the variables of

16

excess weight and age at menarche. Studies demonstrate that an increase in BMI had

17

shown association with decline in physical activity.4 Data from WHO, from 2010,

18

informed that worldwide, 81% of adolescents from which 84% of girls and 74% of

19

boys, aged between 11 and 17 years, are insufficiently active, confirming high rates of

20

sedentary behavior among adolescents (http://www.who.int/end-childhood-obesity/en/

21

accessed in August 2015).

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22

Regarding the limitations of the study, since this is a cross-sectional study, we cannot

23

exclude that factors other than excess weight, may be associated with early age at

24

menarche. Furthermore, considering that the menarche event and the time of data

25

collection did not coincide, changes in habits and lifestyle may have occurred.

18

ACCEPTED MANUSCRIPT There are no comparative studies for the Brazilian region studied, nonetheless our

2

data were correlated with other regions of the country and other countries, in the same

3

way that due to the nature of a cross-sectional study, we cannot exclude other factors

4

(besides excess weight), from being associated to early age at menarche, as well as

5

considering the fact that the menarche event and time of data collection do not coincide,

6

and that during this period changes in habits and lifestyles may have occurred.

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Concerning the use of the questionnaire, despite being a validated method, there is

8

still limitation on the subjectivity of responses. On the other hand, there are few studies

9

that address the issue, particularly in the region studied, which reflect the outcomes of

10

changes in behavior and lifestyle of young Brazilians as a result of the new global

11

economic scenario in the last two decades.

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Conclusion

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This study brings about opportunity for projection, not just for public, but also social

17

and economic health, demonstrating the association of age at menarche with excess

18

weight, the high prevalence of early menarche, as well as its implications for earlier

19

sexual initiation, and pregnancy during adolescence. Furthermore, excess weight and

20

body fat have a negative reflection on fertility and health in adult life.

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Therefore, despite the complexity of regulation in puberty involving genetic,

22

hormonal and environmental mechanisms, studies similar to this one are of extreme

23

relevance, so that plans can be elaborated in face of modifiable factors, and in this

24

context for the education of children and adolescents, as well as their parents; and

25

alerting the family and schools environments, referring to the control of sedentary

19

ACCEPTED MANUSCRIPT 1

behavior and obesity. An urgent strategy is necessary, not only for the individual but

2

also for the community, extending also to education in sexual health, and prevention, for

3

girls that have a tendency for early sexual maturity.

6 7

Acknowledgments

The authors wish to thank the medical school students who assisted in the collection of data, and the school teachers for their patience and valuable assistance.

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References

2

1. Elks CE, Perry JR, Sulem P, et al: Thirty new loci for age at menarche identified

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by a meta-analysis of genome-wide association studies. Nat Genet 2010;

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3. Cheng G, Buyken AE, Shi L, et al: Beyond overweight: nutrition as an

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2. Eisenstein E: Adolescência: definições, conceitos e critérios. Adolesc Saude

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chemicals on tomorrow's women. J Pediatr Adolesc Gynecol 2009; 22:3

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5. Biro FM: Puberty-Whither goest? J Pediatr Adolesc Gynecol 2006; 19:163

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7. Mueller NT, Jacobs DR Jr, MacLehose RF, et al: Consumption of caffeinated

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8. Carvalho WRG, Farias ES, Guerra-Júnior G: A idade da menarca está

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11. Instituto Brasileiro de Geografia e Estatística – IBGE, Diretoria de Pesquisas,

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Coordenação de Trabalho e Rendimento: Pesquisa de orçamentos familiares

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2008-2009: antropometria e estado nutricional de crianças, adolescentes e

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adultos no Brasil, Rio de Janeiro, IBGE, 2010, pp 1-130 12. Goulart AO, Tock L, Carnier J, et al: Etiologia Da Obesidade. In: Obesidade,

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(2nd ed.). Edited by A Dâmaso. Rio de Janeiro, Guanabara Koogan, 2009, pp 3-

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13. Leal VS, Lira PI, Oliveira JS, et al: Excesso de peso em crianças e adolescentes

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no Estado de Pernambuco, Brasil: prevalência e determinantes. Cad Saude

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Publica 2012; 28:1175

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14. Benedet J, de Assis MAA, Calvo MCM, et al: Excesso de peso em adolescentes: explorando potenciais fatores de risco. Rev Paul Pediatr 2013; 31:172 15. Lazzeri G, Rossi S, Pammolli A, et al: Underweight and overweight among

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children and adolescents in Tuscany (Italy). Prevalence and short-term trends. J

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Prev Med Hyg. 2008; 49:13

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onset of puberty. Pediatrics 2007; 119:e624

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16. Lee JM, Appugliese D, Kaciroti N, et al: Weight status in young girls and the

17. Kronenberg HM, Melmed S, Polonsky KS, et al: Williams tratado de endocrinologia (11th ed.), Rio de Janeiro, Elsevier, 2010, pp 1-1560

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18. Demerath EW, Towne B, Chumlea WC, et al: Recent decline in age at menarche: the Fels Longitudinal Study. Am J Hum Biol 2004; 16:453

19. Barbetta PA. Estatística aplicada às ciências sociais (5th ed.), Florianópolis, UFSC, 2004, pp 1-2015. 20. Marshall WA, Tanner JM: Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44:291

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21. Petroski EL: Antropometria: técnicas e padronizações (3rd ed.), Blumenau, Nova Letra, 2007, pp 1-182 22. Bioelectrical impedance analysis in body composition measurement: National

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Institutes of Health Technology Assessment Conference Statement. Am J Clin

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Nutr 1996; 64:524S

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23. Kuczmarski RJ, Ogden CL, Guo SS, et al: 2000 CDC Growth Charts for the

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United States: methods and development. Vital Health Stat 11 2002; (246):1

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24. Slaughter MH, Lohman TG, Boileau RA, et al: Skinfold equations for

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estimation of body fatness in children and youth. Hum Biol 1988; 60:709 25. Domingues da Silva Faria AL, Fernandes da Graça BM, Alvarenga AP, et al:

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Idade da menarca em estudantes de instituições públicas no município de

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Jundiaí, Brasil. Perspectivas Médicas 2014; 25:27

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26. Biro FM, Greenspan LC, Galvez MP: Puberty in girls of the 21st century. J Pediatr Adolesc Gynecol 2012; 25:289

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27. Castilho SD, Pinheiro CD, Bento CA, et al: Tendência secular da idade da

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menarca avaliada em relação ao índice de massa corporal. Arq Bras Endocrinol

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Metabol 2012; 56:195

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28. Al-Awadhi N, Al-Kandari N, Al-Hasan T, et al: Age at menarche and its

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relationship to body mass index among adolescent girls in Kuwait. BMC Public

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Health 2013; 13:29

29. Piancastelli CH, Spirito GC Di, Flisch TMP: Saúde do Adulto (2nd ed.), Belo Horizonte, Nescon/UFMG, 2013, pp 1-183

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30. Cerqueira-Santos E, Paludo S dos S, dei Schirò EDB, et al: Gravidez na

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adolescência: análise contextual de risco e proteção. Psicol Estud 2010; 15:72

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31. Berquó E, Cavenaghi S: Fecundidade em declínio: breve nota sobre a redução

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no número médio de filhos por mulher no Brasil. Novos Estud – CEBRAP 2006;

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(74), 11 32. Nasri F: O envelhecimento populacional no Brasil. Einstein 2008; 6:S4

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33. Oliveira FR, Lemos CNCD. Obesidade e reprodução. Femina 2010; 38:245

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ACCEPTED MANUSCRIPT Table 1. Socio-demographic and behavioral characteristics, and nutritional status of girls with menarche in the southwestern region of the Brazilian Amazon, 2014 and 2015 (n=727). Normal

Late

Menarche

Menarche

Menarche

Variables

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Early

p-

n=380

52.27%

n=298

40.99%

n=49

6.74%

value

SC

0.898

Social class 249

65.5

200

67.1

33

67.3

C and D

131

34.5

98

32.9

16

32.7

Living with parents

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A and B

0.834

180

47.4

146

49.0

22

44.9

Others

200

52.6

152

51.0

27

55.1

Number of siblings ≤ 2 siblings

0.289

282

74.2

230

77.2

41

83.7

98

25.8

68

22.8

8

16.3

EP

> 2 siblings

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Parents

0.502

AC C

Physical activity

Active

218

57.4

168

56.4

32

65.3

Inactive

162

42.6

130

43.6

17

34.7 0.008

Television

≤ 2 hours

154

40.5

122

40.9

31

63.3

> 2 hours

226

59.5

176

59.1

18

36.7 0.119

Tanner stages B2

3

0.8

2

0.7

1

2.0

ACCEPTED MANUSCRIPT B3

95

25.0

68

22.8

12

24.5

B4

173

45.5

168

56.4

24

49.0

B5

109

28.7

60

20.1

12

24.5 0.001

Without excess 245

64.5

237

79.5

135

35.5

61

20.5

weight With excess weight

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BMI z-score

39

79.6

10

20.4

0.015

Without excess 51.1

186

48.9

With excess body fat

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p-value calculated using Chi-square test

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185

62.1

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194 body fat

SC

Body fat %

113

37.9

26

53.1

23

46.9

ACCEPTED MANUSCRIPT Table 2. Association between excess weight and age at menarche in girls from the southwestern region of the Brazilian Amazon, 2014 and 2015, using analysis of multiple logistic regression Gross

Beta

Adjusted

(standard

Odds Ratio

(standard

Odds Ratio

error)

(95% CI)*

Age at Menarche Early

p-value

1

RI PT

Beta

error)

(95% CI)*

p-value

1

-0.761 (0.179)

0.46 (0.32; 0.66)

0.000

-0.748 (0.18)

0.47 (0.33; 0.67)

0.000

late

-0.765 (0.370)

0.46 (0.22; 0.96)

0.039

-0.809 (0.37)

0.44 (0.21; 0.93)

0.032

Constant

-0.596 (0.107)

0.55

0.000

-2.238 (0.53)

0.10

0.000

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* Model adjusted for the following covariates: socioeconomic status, living with parents, number of siblings, physical activity, television viewing and maturity stages; Goodness-of-fit test for the gross

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models"(χ2: 0.000; p = 1.000) and adjusted (χ2: 8.547; p = 0.382).

ACCEPTED MANUSCRIPT Table 3. Association between body fat % and age at menarche, in girls from the southwestern region of the Brazilian Amazon, 2014 and 2015, using the analysis of multiple logistic regression Gross

Beta

Adjusted

(standard

Odds Ratio

(standard

Odds Ratio

error)

(95% CI)*

Age at menarche Early

p-value

1

RI PT

Beta

error)

(IC95%)*

p-value

1

-0.451 (0.157)

0.63 (0.46; 0.86)

0.004

-0.444 (0.162)

0.64 (0.46; 0.88)

0.006

Late

-0.080 (0.304)

0.92 (0.50; 1.97)

0.791

-0.061 (0.316)

0.94 (0.50; 1.74)

0.848

Constant

-0.596 (0.103)

0.95

0.682

-2.529 (0.487)

0.08

0.000

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* Model adjusted for the following covariates: socioeconomic status, living with parents, number of siblings, physical activity, television viewing and maturity stages; Goodness-of-fit test for the gross

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models"(χ2: 0.000; p = 1.000) and adjusted (χ2: 5.099; p = 0.747).

ACCEPTED MANUSCRIPT

Normal

Late

EXCESS WEIGHT (P<0.000)

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SC

20.40%

20.50%

35.50%

37.90%

46.90%

48.90%

Early

EXCESS BODY FAT (P<0.015)

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Figure 1. Excess weight in relation to age at menarche categories of 727 schoolgirls attending primary and secondary schools, located in the southwest region of the Brazilian Amazon, 2014 and 2015.