Obesity Is Associated With Earlier Pubertal Onset in Boys

Alexander S. Busch; Brigitte Højgaard; Casper P. Hagen; Grete Teilmann


J Clin Endocrinol Metab. 2020;105(4) 

In This Article

Materials and Methods

Study Populations

A total of 218 obese (age-specific BMI/zBMI > +2SD) boys (median [range] zBMI: 2.79 [2.01–5.00]), with a median age at baseline of 10.8 years (range 4.2–17.0) were enrolled as part of a longitudinal prospective outpatient childhood obesity intervention program including a thorough clinical workup at The Children's Obesity Clinic, Department of Pediatrics, Nordsjællands Hospital, Hillerød, Denmark, between 2009 and 2017. Despite frequent visits around every 2 months, pubertal development was assessed at inclusion and 1 year after inclusion. After this, additional pubertal assessment was performed, if there was a clinical suspicion for precocious puberty. The median age at puberty assessment was 10.9 (5th–95th interval; 7.1–15.3) years. The examiners were all thoroughly trained by two senior physicians. Secondary diagnoses of chronic diseases in the study cohort includeed allergies (n = 23), asthma (n = 18), attention-deficit/hyperactivity disorder (n = 10), atopic dermatitis (n = 4), psychomotoric retardation (n = 3), epilepsy (n = 2), Asperger syndrome (n = 2), autism (n = 2), cerebral paresis (n = 1), and Tourette syndrome (n = 1). Mixed cross-sectional and longitudinal data on pubertal development was available, as participants underwent pubertal staging once (n = 176), twice (n = 41), or three times (n = 1). As controls, we included 660 healthy boys participating in the COPENHAGEN Puberty Study with a zBMI between -2SD and +2SD (n = 660, cross-sectional data (n = 570) and longitudinal data (n = 90), median age at baseline 10.8 [range: 5.8–19.1]). The COPENHAGEN Puberty Study (ClinicalTrials.gov ID: NCT01411527) is a population-based cohort study of healthy Danish children and adolescents. In brief, the study is a mixed cross-sectional and longitudinal study conducted at 10 schools in the Copenhagen area between 2006 and 2014. A total of 3101 boys were invited to participate in the study, with an overall participation rate ca 25%. Of 799 healthy boys with clinical pubertal staging, we excluded 137 boys due to non- Danish origin (n = 67), history of severe chronic illness (n = 2), or a zBMI/mean zBMI (in the longitudinal cohort) > 2SD or -2SD ≤ (n = 68). The clinical assessment of pubertal development according to Tanner & Marshall, including genital stage (G1–5) and pubic hair (PH1–5), was performed by trained physicians in both cohorts. "Scrotal enlargement and change in texture of the scrotal skin" and "sparse development of pigmented hair at the base of penis" defined genital stage G2 and pubic hair stage PH2, respectively.[12] In addition, testicular volume was measured using a Prader orchidometer to the nearest mL. Pubertal timing in male participants of the COPENHAGEN Puberty Study has previously been published.[5]

Statistical Analyses

Timing of pubertal milestones was estimated by lifereg analyses (SAS: proc lifereg). Proc lifereg allows integrating left- (n = 98), right- (n = 108), and interval- (n = 12) censored observations and yes/no to "event occurred" as the binary response variable. Children experiencing a pubertal event during a follow-up were included as interval-censored data (their age at the last visit without the pubertal event and their age at the last visit with the occurred pubertal event). Data was included as right censored data if a child had not experienced the event at his last examination (or at the only examination, if seen once), and data was included as left censored data if a child had experienced the event at his first examination (or at the only examination, if seen once). Age-specific body mass index scores were obtained by comparison to the WHO 2007 reference.[13] For individuals with longitudinal data on pubertal status, a mean BMI z-score across all visits was calculated. Since zBMI > +5SD is not defined in the WHO reference, data points exceeding 5 zBMI were set to 5 (n = 4). Pubertal development in obese boys was compared to puberty reference data, that is, puberty nomograms, based on Danish boys from the cross-sectional part of the COPENHAGEN Puberty study.[14] We did not collect data on inter-observer reliability systematically. However, the interobserver reliability for orchidometer has previously been observed to be sufficiently high, that is, with an intraclass correlation coefficient of 0.97.[15] Likewise, the intraclass correlation coefficient for the genital and pubic hair stages in boys was found to be high, that is, 0.94 and 0.83, respectively.[16] A P value < 0.05 was considered statistically significant.

Ethical Considerations

The study at Nordsjællands Hospital has been approved by the Danish Data Protection Agency (journal number: 2007-58-0015 and NOH-2014-020-03092). All custody holders of the participants gave written consent for participation in the treatment. The study is considered to be a prospective observational quality development study. Therefore, notification to the National Committee on Health Research Ethics or to the National Board of Health was not required (Ref: H-2-2014- FSP59). The COPENHAGEN Puberty Study was approved by the ethical committee of The Capital Region of Denmark (No. KF01282214) as well as the Danish Data Protection Agency (No. 2015–41-4494).