Early Pituitary-Gonadal Activation before Clinical Signs of Puberty in 5- to 8-Year-Old Adopted Girls: A Study of 99 Foreign Adopted Girls and 93 Controls

Context: Recent studies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Clinical studies including a contemporary control group are lacking. Objective: The objective was to study clinical, biochemical, and ultrasonographic markers of pituitary-gonadal activation in prepubertal adopted girls and a control group in the same age categories. Setting: The study took place at University Hospital, Copenhagen, Denmark. Design and Participants: The study included randomly selected internationally adopted girls [(n = 99; mean age, 6.9 (5.1–8.5) yr] and controls of Danish origin [n = 93; mean age, 6.8 (5.2–8.5) yr] who were studied cross-sectionally. Methods: Height, weight, and pubertal stage were assessed with serum levels of reproductive hormones. Size and morphology of internal genitals were evaluated by ultrasonography. Bone age was evaluated by x-ray of the left hand. Results: Serum values of FSH were significantly higher in prepubertal adopted girls compared with controls [median, 1.4 (95% confidence interval, 0.4–3.6) vs. 1.0 (0.4–2.4) IU/liter; P <0.001]. Serum estradiol was above detection limit (>18 pmol/liter) in 46.5% of prepubertal adopted girls and 20.7% of controls (P = 0.001). In prepubertal adopted girls, the proportion of measurable samples increased significantly with age [odds ratio, 2.5 (95% confidence interval, 1.3–5.0; P = 0.009]. In controls, the odds ratio was 1.0 (0.6–1.7) (P = 0.9). Serum SHBG levels were significantly lower in prepubertal adopted girls compared with controls [99.0 (50.4–153.0) vs. 115.0 (53.1–202.1); P < 0.001]. Conclusion: Five- to 8-yr-old adopted girls showed signs of increased pituitary as well as gonadal activity despite prepubertal phenotype in the majority of girls. Our findings suggest that early onset of puberty in adopted girls is centrally driven.