Hormonal changes during GnRH analogue therapy in children with central precocious puberty

Gonadotropin releasing hormone analogues (GnRHa) have been used for treatme nt of central precocious puberty (CPP) for more than 15 years, They are gen erally considered safe although data on potential long-term side effects ar e scarce. However, GnRHa therapy has profound effects on both the hypothala mopituitary-gonadal axis as well as on growth hormone (GH) secretion. Gonad al activity is increased in children with CPP; during GnRHa therapy secreti on of gonadal hormones is suppressed as reflected by measurements of LH, FS H, and estradiol/testosterone. More recently, studies of levels of inhibin A and B as well as markers of androgen action such as SHBG and prostate spe cific antigen have demonstrated marked suppression of gonadal function poss ibly to infra-physiological levels, The possible long-term consequences of these observations have yet to be determined. Detailed analyses of the GH-I GF-I axis have revealed a decrease in levels of free, biologically active I GF-I during GnRHa treatment. These findings are in accord with the observed decrease in height velocity in children with CPP under treatment with GnRH a, and may also play a role in the relatively small gain in final height in most patients.