Growth, bone maturation and ovarian size in girls with early and fast puberty (EFP) and effects of three years treatment with GnRH analogue (GnRHa)

INTRODUCTION: Early puberty (EP) in girls is defined as the onset of thelarche that begins after 6 years and before 8 years and/or acceleration in the tempo of pubertal development. The stage of puberty and the ovarian volume at presentation and the effect of treatment with GnRH analogue (GnRHa) on final adult height are still debated. PATIENTS AND METHODS: We analyzed the data of 22 girls, who presented early and fast puberty (FEP). The clinical stage of puberty, hormonal levels, and ovarian volume (OV) (measured by ovarian ultra-sonography) at presentation were studied. We recorded the effects of 3 years of treatment with GnRHa on their growth in relation to their mid parental height, pubertal progression, and bone maturation. RESULTS: At presentation, the mean age of girls was 7.7 ± 0.7 yr , Ht-SDS was 0.8 ± 0.9, and growth velocity (GV) was 8.7 ± 1.4 cm. Bone age was advanced by 1.9 ± 1 yr compared to their chronological age. The difference between their standing height (Z-Score: Ht-SDS) and their mid-parental Ht-SDS (MPht-SDS) was 1.4 ± 0.7. Their predicted final adult height (FA-Ht) was 155 ± 8cm. After 3 years of using GnRHa (Triptorelin:3.75 mg I.M. monthly), their mean Ht-SDS was 0.5 ± 1.5, associated with reduced growth velocity (GV: 5 ± 1.5 cm/yr) and deceleration of bone age (0.7± 0.8 yr compared to their chronological age). The difference between their Ht-SDS and their MPht-SDS was 1.2 ± 1 and their predicted FA-Ht improved to 159 ± 9cm. Their average MPht was 159 ± 4 cm. There was no change in breast development during the 3 years of therapy. The BMI-SDS significantly increased from 1.3 ± 0.7 before treatment to 1.7 ± 0.8 after 3 years of treatment (P = 0.001). At presentation, the mean OV was 2.3 ± 1.2mL. The OV correlated significantly with breast and pubic hair Tanner stages (r = 0.34, and 0.56, respectively; P: < 0.05). There was also a significant correlation between OV and the hormonal profile (LH, FSH, 17β-estradiol and IGF-1 levels; r = 0.80, 0.54, 0.485 and 0.40, respectively; P: < 0.05). There was no correlation between OV and bone age. Larger OV at presentation was associated with reduced Ht-SDS after 3 years of GnRHa treatment (r = 0.42, P: < 0.01) and negatively with the difference between Ht-SDS and MPH-SDS at the end of treatment (lower potential for growth; r =0.47, P: < 0.01). CONCLUSION: GnRHa therapy decreased the fast progress of puberty, skeletal maturation, and GV/year. It was successful in increasing the predicted final adult height comparable to or surpassing their mid-parenteral height. A larger OV at presentation was associated with reduced Ht-SDS after 3 years of GnRHa treatment. Clearly, a definitive evaluation of the efficacy of GnRHa as a treatment for EFP in girls will require expanded and concerted studies. (www.actabiomedica.it)