Serum Sex Hormone-Binding Globulin Levels in Healthy Children and Girls with Precocious Puberty before and during Gonadotropin-Releasing Hormone Agonist Treatment

Abstract

The regulation of SHBG is complex and influenced by sex steroids and insulin. Our objective was to describe serum levels and evaluate determinants of SHBG levels in healthy children and in girls with central precocious puberty (CPP) before and during GnRH analog (GnRHa) treatment. We conducted a cross-sectional study on healthy subjects and a 2-yr longitudinal study in girls with CPP. The study took place at a tertiary referral center for pediatric endocrinology. A total of 903 healthy schoolchildren served as healthy subjects, and 25 girls with precocious/early puberty participated. Girls with CPP were treated with the long-acting GnRHa triptorelin. SHBG levels declined with increasing age in both sexes until adulthood. In healthy children, SHBG was significantly negatively correlated with testosterone, estradiol, dehydroepiandrosterone sulfate, and body mass index (BMI) in boys (total model R(2) = 0.71) but only with dehydroepiandrosterone sulfate and BMI in girls (total model R(2) = 0.26). Body fat percentage was significantly negatively correlated with SHBG levels (P < 0.001) in both boys (R(2) = 0.18) and girls (R(2) = 0.23). Girls with CPP had significantly lower pretreatment SHBG levels compared with age-matched controls [SHBG sd score, -1.29 (-4.48; 0.01)], which declined even further during GnRHa treatment [-2.75 (-5.9; 0.53); P < 0.001]. Even after adjustment for BMI and pubertal stage, girls with CPP had lower SHBG levels (P < 0.001) compared with healthy controls. SHBG levels were strongly dependent on body composition and sex steroid levels in children with normal and precocious puberty. Studies on insulin sensitivity and SHBG in puberty are needed to better understand the interaction between body composition and gonadal maturation.