In order to assess the behavior of growth hormone, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) in girls with central precocious puberty treated with gonadotropin-releasing hormone (GnRH) analog-therapy, we studied 14 girls with this condition, the patients were subdivided into two groups, according to the therapy followed. Group A (n = 7; age 4.2-7.1 years) received GnRH analog in combination with cyproterone acetate, and Group B (n = 7; age 4.4-6.9 years) received long-acting analog alone. Before treatment, IGF-I levels were significantly increased compared to healthy age-matched children in the two groups (447 +/- 33 micrograms/l for Group A and 435 +/- 38 micrograms/l for Group B vs. control 175 +/- 78 micrograms/l; p < 0.01). Moreover, serum IGFBP-3 levels were significantly higher than the age-related reference range for IGFBP-3 (4478.2 +/- 178 micrograms/l for Group A and 4532.3 +/- 167 micrograms/l for Group B vs. control 2905 +/- 641 micrograms/l; p < 0.01). During the two years of gonadal suppression, Group A patients showed a significant decrease in IGF-I and IGFBP-3 levels, while in Group B there was no significant change in IGF-I; moreover, in Group B, IGFBP-3 levels increased significantly compared to baseline values during the first year of treatment (4532.3 +/- 167 micrograms/l vs. 5410.3 +/- 169 micrograms/l; p < 0.05) and decreased significantly at the end of the second year of treatment (3816.1 +/- 189 micrograms/l vs. 5410.3 +/- 169 micrograms/l; p < 0.01). Our study shows that the two different treatments of precocious puberty (with and without cyproterone acetate) have different effects on IGF-I and IGFBP-3, and suggests that these growth factors are under different metabolic regulation.