Adiposity, Chronic Inflammation and the Prepubertal Decline of Sex Hormone Binding Globulin in Children: Evidence for Associations with the Timing of Puberty (EarlyBird 58).

Background: The regulation and role of Sex Hormone Binding Globulin (SHBG) in children are poorly defined. Here we investigated whether adiposity-related mechanisms regulate SHBG and whether SHBG levels are associated with the age of puberty. Methods: Longitudinal modelling of annual physiological and endocrine measurements from age 5-15 years in a cohort of 347 Plymouth schoolchildren. Results: SHBG levels were highest at age 5 and then declined. Mean (SE) SHBG levels were higher in boys than girls at age 5 (mean (SE) difference 7.68 (3.80) nmol/l; p=0.045), but lower in boys by age 15 (difference 12.19 (3.4) nmol/l; p<0.001). SHBG correlated inversely with adiposity (BMIsds), insulin, IGF-1, C-reactive protein (CRP) and leptin, positively with adiponectin, but not with dehydroepiandrosterone sulphate (DHEAS), androstenedione or testosterone. In linear mixed models, five adiposity-related covariates - insulin, leptin, adiponectin, IGF-1 and CRP - all exerted significant main effects on SHBG (boys 0.04>p<0.001; girls 0.007>p<0.001). However, the further addition of BMIsds rendered effects of leptin, insulin and adiponectin non-significant, whereas CRP and IGF-1 remained significant. In separate models, the individual effects on SHBG of insulin, leptin, IGF-1 and adiponectin, but not CRP, were displaced by BMIsds. Finally, in linear regression, BMIsds little affected R-square resulting from the five adiposity-related signals. Girls with lower SHBG levels at age 5 reached Tanner stage 2 earlier, tended to have earlier LH secretion, age at peak height velocity (APHV) and menarche. In contrast, boys with lower SHBG levels at age 5 reached Tanner stage 2 earlier, but there were no relationships between SHBG and earlier onset of LH secretion or APHV. Conclusions: Adiposity-related endocrine mechanisms and chronic inflammation were associated with the prepubertal decline of SHBG, and lower SHBG levels anticipated earlier puberty. These findings may be relevant to the occurrence of earlier puberty in recent decades.