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

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, AUC0(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.

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