Gonadotrophin-Releasing Hormone Analogues as Therapeutic Probes in Human Growth and Development: Evidence from Children with Central Precocious Puberty

ABSTRACT. Statural growth and skeletal development were assessed in 87 girls with idiopathic central precocious puberty (CPP) during gonadotrophin-releasing hormone analogue (GnRHa)-induced suppression of gonadarche. Before the start of therapy, mean chronological age (CA) was 6.3 years and mean bone age (BA) was 10.6 years. During up to 6 consecutive years of complete suppression of gonadal sex steroid secretion, the mean height velocity decreased from 10.8 cm/year to prepubertal rates. At each interval height velocity was found to be inversely and negatively correlated with BA such that girls with advanced BAs grew at rates well below prepubertal norms but appropriately for their degree of skeletal maturation. Skeletal maturation similarly slowed during prolonged GnRHa administration (ABA/ACA = 0.6 ± 0.1 over 3 years, mean ± SD, n = 66) and was also negatively correlated with the BA before the start of therapy. Predicted adult height increased progressively during therapy; however, when analysed as changes in height SDS(BA), the impact of treatment was variable and correlated positively with the initial degree of skeletal maturation. The effect of GnRHa therapy on growth in children with CPP requires long-term study and is best analysed by employing a developmental perspective.     

Gonadotrophin-Releasing Hormone Agonist Treatment of Central Precocious Puberty: an Analysis of Growth Data in a Developmental Context

ABSTRACT. Growth and skeletal maturation was assessed in 83 girls with central precocious puberty (CPP) during pituitary—gonadal suppression induced by treatment with a gonadotrophin-releasing hormone agonist (GnRHa). The mean pretreatment chronological age (CA) was 6.3 years and the mean bone age (BA) was 10.6 years. During the suppression of gonadal sex steroid secretion, mean height velocity (HV) decreased from a pretreatment value of 10.8 cm/year to 5.9 (year 1, n = 83), 4.9 (year 2, n = 72), 4.2 (year 3, n = 49, and 4.4 (year 4, n = 23) cm/year. During each interval, there was a negative correlation between HV and the pretreatment BA. In addition, the rate of skeletal maturation was reduced during GnRHa treatment (ΔBA/ΔCA = 0.6 ± 0.1 over 3 years, n = 45). The rate of skeletal maturation during therapy was also negatively correlated with pretreatment BA. Predicted adult stature, based upon z -scores of height for BA, increased significantly and progressively during therapy but the changes in height SDS for BA varied significantly. Since HV, ΔBA/ΔCA, and the change in height SDS for BA (ΔHT SDS for BA) during pituitary—gonadal suppression all correlated with the initial degree of skeletal maturation, the effect of GnRHa therapy on Final adult height in children with CPP will be best understood if growth data are assessed within a developmental framework.     

Reproductive outcome in patients treated and not treated for idiopathic early puberty: long-term results of a randomized trial in adults

OBJECTIVE: To evaluate the adult reproductive outcome in girls with early puberty who participated in a previous random study. STUDY DESIGN: A total of 22 subjects treated with triptorelin 3.75 mg every 4 weeks (group 1), 18 subjects not treated (group 2), and 22 age-matched normal volunteers (control group) underwent a physical examination, serum hormone level determination, and pelvic ultrasonography. RESULTS: The characteristics of menstrual cycles, serum hormone levels, and ultrasound results did not differ significantly among the 3 groups examined. The mean ovarian volume and the uterine volume tended to increase in the subjects of group 2, but the differences were not significant. The percentage of subjects who reported being sexually active at the time of the examination was greater in the 2 groups with previous early puberty than in the controls (76% of cases in group 1, 72% in group 2, and 59% in the control group). CONCLUSIONS: Neither early puberty nor its treatment seems to significantly affect the normal adult function of the pituitary-gonadal axis.