Sex steroids and adiposity in a prospective observational cohort of youth

Abstract

Objective Adiposity, particularly visceral adipose tissue (VAT), predicts adverse cardiovascular risk factor profiles in children as well as adults. Although endogenous sex steroids likely influence VAT in adults, such an association has not been established in youth. The association between childhood and adolescent sex steroids with adiposity, specifically VAT, was examined before and after adjustment for other hormone changes. Methods These analyses examined longitudinal associations between sex steroids (testosterone, estradiol, dehydroepiandrosterone [DHEA]) and magnetic resonance imaging assessments of VAT in 418 children, 49% of whom were non‐White, at approximately 10 years old at Visit 1 (V1) and 17 years old at Visit 2 (V2). Linear mixed effects models adjusted for maternal education, household income, child caloric intake, physical activity, fasting insulin and leptin, and hepatic fat fraction. Differences in associations by race and pubertal stage were also assessed. Results At V1, mean body mass index (BMI) for boys was 19.1 (4.7) kg/m2 and for girls was 18.5 (4.1) kg/m2. At V2, mean BMI for boys was 23.7 (5.5) kg/m2 and for girls was 23.6 (5.7) kg/m2. For each ng/dl (0.035 nmol/L) increase in testosterone at V1, there was a 0.25 cm2 increase in concurrent and future VAT in non‐White (p = 0.04) but not White girls (p = 0.78). Higher levels of testosterone and DHEA at V1 were associated with greater concurrent and future VAT at V2. These associations were consistent regardless of pubertal stage. In boys, higher testosterone predicted higher future VAT but lower concurrent VAT. Estradiol and DHEA did not predict future VAT in boys. In girls, DHEA predicted future subcutaneous adipose tissue (SAT), and no sex steroids predicted future SAT in boys. Conclusions Testosterone levels predict VAT in boys and girls, and DHEA predicts VAT in girls, even after adjustment for other hormone changes.

Epigenetic age acceleration is associated with speed of pubertal growth but not age of pubertal onset

“…To some extent, this reflects the fact that greater fat mass is associated with lower testosterone in boys, since this association was partially mediated by the various fat measures available in EPOCH. In previous EPOCH reports 19 , 37 , more rapid accumulation of VAT or SAT was associated with lower testosterone independent of confounders including age, insulin and leptin levels.…”

The role of prenatal maternal sex steroid hormones in weight and adiposity at birth and growth trajectories during infancy

“…This evidence could explain how high maternal testosterone levels were associated with lower birthweight, particularly in male fetuses. Furthermore, testosterone has been implicated in promoting visceral preadipocyte proliferation and adiposity in human (13,47), with sex-speci c responses likely in uenced by sex dimorphism in adipose tissue biology, such as differential expression of sex steroid receptors in adipose tissue, the number of adipocyte precursor cells, and differential programming by sex chromosome (27). Additionally, testosterone interacts with epigenetic enzymes and can regulate epigenetic modi cations (48), potentially in uencing postnatal growth and adiposity.…”