Reduced levels of GH during GnRH analogue treatment in pubertal short girls born small for gestational age (SGA)

Abstract

Context: Several studies showed a decrease in height velocity during GnRH analogue (GnRHa) treatment. No information is available on GH levels during GnRHa treatment in short SGA girls.

Objective: To study overnight GH profiles and IGF-I and IGFBP-3 levels in girls with Tanner stage 2 and stage 3, before and after 3 months of GnRHa treatment, and to compare levels with those found in prepubertal short SGA girls.

Patients: Twenty-four pubertal and 16 prepubertal short SGA girls.

Intervention: After baseline overnight GH profiles, pubertal girls received leuprorelide acetate depots of 3.75 mg subcutaneously every 4 weeks.

Outcome measures: GH, IGF-I and IGFBP-3 levels.

Results: At baseline, GH levels were comparable to levels found in prepubertal short SGA girls and IGF-I and IGFBP-3 SDS were significantly below the population mean. After 3 months of GnRHa treatment, AUC(0) (P = 0.02), mean (P = 0.02) and maximum GH levels (P = 0.008) had significantly decreased. Mean GH levels were significantly lower than in prepubertal short SGA girls (P = 0.03). Eight girls with more than 40% decrease in mean GH levels also had a significantly greater decrease in IGF-I and IGFBP-3 levels. Mean and maximum GH levels at baseline correlated significantly with those after 3 months of GnRHa treatment.

Conclusion: Short SGA girls lack the normal increase in GH levels seen in puberty and have reduced IGF-I and IGFBP-3 levels, which might explain their reduced pubertal growth spurt. GnRHa treatment led to a significant reduction in GH levels. Therefore, combining GnRHa treatment with GH treatment might improve adult height of short SGA girls.