The Relationship Between Luteinizing Hormone and Estradiol Secretion in Female Precocious Puberty: Evaluation by Sensitive Gonadotropin Assays and the Leuprolide Stimulation Test

We used the GnRH agonist (GnRHa) stimulation test (20 micrograms/kg leuprolide sc, followed by 24-h serial sampling) to investigate the relationship between gonadotropin and estradiol (E2) secretion in the early phase of female central precocious puberty (CPP). Girls with CPP and moderately increased (early pubertal) peak E2 concentrations after GnRHa stimulation (136 +/- 11 pmol/L; range, 92-176; group B; n = 7) were compared to girls with CPP and higher (midpubertal) peak E2 responses to GnRHa (mean +/- SE, 590 +/- 63 pmol/L; range, 235-1189; group C; n = 19) and to a group of subjects with no breast development and a prepubertal hypothalamic-pituitary-gonadal axis (peak E2 response to GnRHa, 39 +/- 7 pM/L; range, 18-62; group A; n = 6). Compared to group A subjects, patients in group B had similar (P > 0.2) peak GnRHa-stimulated LH concentrations (B, 4.8 +/- 1 IU/L; A, 2.3 +/- 0.5 IU/L) and peak nocturnal LH (B, 0.81 +/- 0.2; A, 0.25 +/- 0 IU/L), but higher peak GnRHa-stimulated FSH concentrations (B, 26 +/- 7; A, 11 +/- 2 IU/L; P < 0.05) and mean nocturnal FSH (B, 4.2 +/- 1; A, 1.1 +/- 0.3 IU/L; P < 0.05) concentrations. Compared to group B, group C patients had higher (P < 0.001) GnRHa-stimulated peak LH (67 +/- 19 IU/L) and higher (P < 0.05) peak nocturnal LH (9.7 +/- 2.9 IU/L) concentrations, but similar GnRHa-stimulated peak FSH (27 +/- 3 IU/L) and mean nocturnal FSH (3.8 +/- 0.5 IU/L) levels. Group C patients with a ratio of peak GnRHa-stimulated LH to FSH concentrations below or above 1, respectively, had similar peak E2 responses to GnRHa (516 +/- 80 vs. 644 +/- 92 pM/L; P > 0.1). Stepwise regression analysis indicated that the peak LH response to GnRHa (r = 0.76; P < 0.001), but none of the FSH secretory parameters (P > 0.10), affected the E2 response to GnRHa. These data suggest that girls with CPP in the early phase of activation of the hypothalamic-pituitary-gonadal axis are capable of clinically relevant E2 production, which may occur in the face of low LH secretion and low LH/FSH ratios and cannot be explained solely on the basis of increased FSH secretion. Thus, endocrine or paracrine factors other than gonadotropins may be important in amplifying E2 secretion in the early phase of CPP.