Adrenal androgens, estrone, and insulin-like growth factor 1 are associated with thelarche without gonadotropin activation in girls.

INTRODUCTION: Although a well-known phenomenon, the hormonal mechanism of thelarche in the absence of gonadotropin activation remains unclear. To reveal the biological mechanisms of such thelarche we assessed serum concentrations of several hormones potentially related to breast development, as well as clinical signs of androgen action. METHODS: A population-based sample of 175 girls aged 9-11 was divided into those without thelarche (Tanner breast stage 1) and those with thelarche (Tanner breast stage ≥ 2). The girls were further categorized based on basal serum luteinizing hormone (LH) using a cut-off of 0.3 IU/L. This resulted in three groups: 114 girls with low LH without thelarche, 32 girls with low LH and thelarche, and 29 girls with higher LH and thelarche. Serum concentrations of sex steroids and insulin-like growth factor-1 (IGF-1) and clinical signs of androgen action were assessed at ages 7-9 and 9-11 years. RESULTS: Girls with low LH and thelarche had higher levels of dehydroepiandrosterone sulfate (DHEAS) (0.80 vs. 0.60 µmol/L, p=0.03 at 7-9 years; 0.97 vs. 0.72 µmol/L, p=0.03 at 9-11 years), testosterone (0.18 vs. 0.14 nmol/L, p=0.02; 0.27 vs. 0.22 nmol/L, p=0.02), estrone (14.5 vs. 11.5 pmol/L, p=0.02; 24.3 vs. 18.2 pmol/L, p=0.002), and IGF-1 (28.6 vs. 23.6 nmol/L, p=0.001; 35.9 vs. 31.1 nmol/L, p=0.006) than girls with low LH without thelarche. Differences in DHEAS, testosterone, and IGF-1 diminished after further adjustment for body fat percentage. Girls with low LH and thelarche also had more clinical signs of androgen action at both ages than girls with low LH without thelarche. There were no statistically significant differences in hormonal concentrations at 7-9 years between girls with low LH and thelarche and those with higher LH and thelarche. However, at 7-9 years, girls with low LH and thelarche had more signs of androgen action than girls with higher LH and thelarche. At 9-11 years, girls with higher LH and thelarche had higher hormonal concentrations except for DHEAS than girls with low LH and thelarche. CONCLUSION: Thelarche with low LH is associated with elevated DHEAS, testosterone, estrone, and IGF-1 concentrations, which is partly explained by BF%, suggesting that aromatization of adrenal androgens to estrogens in adipose tissue is one hormonal mechanism of thelarche in girls without gonadotropin activation.