The Observation Of Combined Use Of Gonadotropin-releasing Hormone Analogues And Growth Hormone In Central Precocious Puberty

Objective Central precocious puberty (CPP), also known as gonadotropin-releasing hormone (GnRH)-dependent precocious puberty, is due to hypothalamic-pituitary-gonadal axis (HPGA)) early start, early secretion of GnRH to activate the gonadal axis, stimulate the pituitary’s secretion of gonadotropins, results in gonadal development, and thus causes the emergence of the external genitalia and secondary sexual characteristics.Gonadotropin-releasing hormone analogue (GnRHa) is the standard drug of current international treatment of central precocious puberty (CPP) which can effectively inhibit the activity of the hypothalamic-pituitary-gonadal axis (HPGA),suppress the secretion of sex hormone, slow the progress of bone age (BA) and improve the adult height. For most children, early and adequate treatment of GnRHa can improve adult expected height effectively. However, some children’s bone age increaes so rapidly that it impairs growth potential and predicted height is often not ideal. Therefore, how to improve the height better is particularly important. This study is to oberve the effect of the use of GnRHa alone and combined use of GnRHa and recombinant human growth hormone (rhGH) in the treatment of central precocious puberty in girls. Method Girls of central precocious puberty were recruited from our hospital between September2008～February2012The inclusion criteria was:1. Secondary sexual characteristics appeared under8years of age;2. Serum gonadotropin levels reached puberty level;3.Gonads increased;4. Linear growth accelerated;5. Bone age>1year;6. Organic diseases were excluded. And those children’s bone age progressed rapidly, impaired growth potential, predicted adult height failed to meet the genetic target height or the ideal height, they were indicated for GnRHa.40patients met the criteria.20cases were treated with GnRHa plus GH,the other20cases were given GnRHa alone. The two groups of children were matched for age, bone age and height and there were no significant difference between them.No children showed growth hormone deficiency. The informed consent was signed. The monotherapy group was given subcutaneous injection of GnRHa at a dose of100μg/(kg), every28～32days. The combined treatment group was given additional subcutaneous injection of rhGH at a dose of0.3mg/(kg week),in order to observe the efficacy of the two different drugs. The treatment time of the two groups both reached one year(1.45±0.32year and1.68±0.40year) Results1.Patients of the group treated with GH plus GnRHa showed an predicted adult height significantly higher than pretreatment (158.45±3.55cmVS150.76±2.42cm), the difference was statistically significant (P<0.05), and reached the genetic target height158.18cm. Predicted adult height in the group treated with GnRHa alone was also increased (154.68±2.83cmVS151.41±1.95cm), the difference was statistically significant (P<0.05), but failed to reach genetic target height159.29cm.2. Standard deviation scores of bone age (HtSDSBA) in combined treatment group and monotherapy group was statistically significant than pretreatment, but the HtSDSBA of combination group increased more significantly, from-1.89±0.42to-1.05±0.46, the monotherapy group group increased from-1.89±0.29to-1.64±0.28.3. The growth rate of the combined treatment group was7.53±0.73cm/year and was faster than the monotherapy group with the growth rate of4.92±0.41cm/year, but there was no significant difference of△bone age/△chronologial age between the two groups. Body mass index (BMI) was increased after treatment in both roups.△BMI is1.01±1.20kg/m2in the monotherapy group and is bigger than combined treatment group with△BMI of0.61±1.17kg/m2, but there was no significant difference (P>0.05)and both in the normal range. No adverse effect was observed in both groups during treatment. Conclusion For children with idiopathic central precocious puberty whose growth potential damaged and predictd adult height was not ideal, combined therapy of GnRHa and GH can improved predicted adult height better than treatment with GnRHa alone. Combination therapy improved height difference scores of bone age significantly and accelerated growth rate in children while bone age was no significant increased. Short-term combination therapy of GnRHa and GH had no significant effect with BMI and no side effect was observed.