Childhood Adiposity and Adolescent Sex Steroids in the Exploring Perinatal Outcomes Among Children Study

Catherine Kim; Kylie K. Harrall; Deborah H. Glueck; Daniel Shumer; Dana Dabelea

Disclosures

Clin Endocrinol. 2019;91(4):525-533. 

In This Article

Abstract and Introduction

Abstract

Objective: It is unclear how childhood adipose tissue deposition influences sex hormone profiles in later adolescence.

Design: Prospective cohort study.

Participants: Children (n = 418) with a mean age of 10.5 (1.5) years at visit 1 and 16.7 (1.2) at visit 2 in the Exploring Perinatal Outcomes among Children (EPOCH) Study.

Measurements: We used reverse-scale Cox proportional hazard models to assess associations between pubertal dehydroepiandrosterone (DHEA), testosterone (T), and oestradiol (E2) and childhood-to-puberty rate of change in visceral (VAT) and subcutaneous adipose tissue (SAT). Models stratified by sex and adjusted for childhood adiposity, maternal factors, birthweight and pubertal onset, and then further adjusted for insulin, luteinizing hormone (LH), leptin and hepatic fat fraction.

Results: Among boys, more rapid accumulation of either VAT or SAT was associated with lower testosterone at visit 2 (HR 0.86, and .96, respectively, both P < .0001), independently of race/ethnicity, LH, leptin and hepatic fat fraction. Among boys, more childhood VAT was associated with lower testosterone in adolescence (HR 0.98, P = .003), but this association did not persist after adjustment for leptin or insulin. No associations were observed between either fat measure and oestradiol or DHEA in boys. In girls, no associations between childhood fat or fat accumulation and sex hormones were observed.

Conclusions: More rapid accumulation of fat is associated with lower testosterone in boys. These associations suggest that fat growth influences androgen profiles in adolescent boys. Since fat accumulation is a modifiable risk factor, the study results provide a possible intervention target and time period for improving adult health.

Introduction

The pubertal transition represents a period of dramatic alterations in body composition and sex hormone profiles. Previous reports in girls[1–4] suggest that obesity is associated with earlier onset of puberty and hyperandrogenemia, whereas the opposite may be true in boys.[5,6] As most of these reports were cross-sectional, it is unclear whether the speed of fat accumulation or baseline body fat influenced the onset of puberty, and to what extent sex steroid hormones as opposed to other markers of puberty were altered. How growth in specific adipose tissue depots, particularly visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), are associated with sex profiles in adolescence is also not established. Finally, adipose tissue production of leptin may stimulate gonadotropin secretion and luteinizing hormone (LH) release as well as insulin resistance, but whether the associations between fat accumulation and sex hormones occur after accounting for luteinizing hormone (LH), fasting insulin, hepatic fat deposition and leptin has not been studied.

The Exploring Perinatal Outcomes in Children (EPOCH) study is a longitudinal cohort study of youth in Colorado.[7] Approximately 418 children had magnetic resonance imaging (MRI) assessed VAT and SAT during prepuberty and early puberty, followed by repeated adiposity and sex hormone measures six years later. In this report, we examined the associations between baseline VAT and SAT in childhood, and growth rate in VAT and SAT with sex hormone levels later in adolescence. We also examined whether these associations changed after adjusting for potential mediators including LH, fasting insulin, hepatic fat and fasting leptin concentrations. Based on previous studies in children, we hypothesized that greater VAT and VAT growth would be associated with higher testosterone levels in girls at the follow-up visit,[1–4] whereas greater VAT and VAT growth would be associated with lower testosterone levels in boys.[5,6] Based on studies in adult women,[8] we also hypothesized that greater SAT would be associated with higher oestradiol levels in girls at the follow-up visit.

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