Is a Combination of a GnRH Agonist and Recombinant Growth Hormone an Effective Treatment to Increase the Final Adult Height of Girls with Precocious or Early Puberty?

Abstract

The aim of treatment for idiopathic central precocious puberty (ICPP) is to increase final adult stature, for which gonadotropin-releasing hormone agonist (GnRHa) is the gold standard. Early puberty is frequently similar to ICPP, with pubertal onset only slightly advanced. Short stature may result from early pubertal onset. Some studies have suggested that recombinant human growth hormone (rhGH) should be combined with a GnRHa to improve adult height, while others have not. Here, the aim was to compare the efficacy of combined GnRHa and rhGH treatment with GnRHa or rhGH treatment alone, or no therapy, for the improvement of the final height of girls with ICPP or early puberty. Electronic databases of randomized and quasi-randomized controlled trials, in which the efficacy of GnRHa preparations was compared with that of rhGH for the treatment of children with precocious or early puberty, were searched and a meta-analysis conducted. Five studies of early puberty and four studies of ICPP were identified. There were no statistically significant differences between final adult height standard deviation score and initial height standard deviation score in the treatment of early puberty (GnRHa and rhGH versus rhGH alone or no treatment). The overall analysis of the data failed to indicate any benefit of combined therapy, while individual reports suggested that in specific instances combined therapy may be beneficial in preserving or reclaiming growth potential and improving adult height.

The Effects of gonadotropin-releasing hormone analog and a combination of gonadotropin-releasing hormone analog and recombinant human growth hormone on adult height in girls with early puberty

“…[491718] Song et al in a meta-analysis from five studies of EP girls concluded that combination therapy could not significantly differ between final adult height SDS and initial height SDS in treated EP girls. Although individual reports suggest the beneficial effects of combined therapy on improving adult height[5] again, the controversies of view exist between experts in this field toward combined therapy, especially when the cost of drugs is too high. There is a report from China on GnRHa and rhGH in combination or GnRHa alone on the treatment of EP girls which argue that PAH at the end of combined therapy was higher than GnRHa alone, although the different was insignificant and both treatments had a similar effect on the final height of EP girls.…”

“…Early puberty (EP) is due to the activation of GnRH pulse generator in lower ages, occurring often in girls;[5] EP may be a potential cause for impairment of adult height. In EP girls, the pubertal onset is slightly advanced, leading to a short stature which may impose psychological problem both in children and parents.…”

“…GnRH analogs are the drug of choice in treatment of children with central precocious puberty (CPP) and also are used in treatment of girls with EP; although in this regard, some available data have reported minimal change on growth outcome in EP girls. [78] Retarded GnRH analogs are used to induce a biochemical and clinical suppression of HPG axis leading to a retardation and/or delay in bone age (BA) and secondary sexual characteristics, decrease pubertal progress, and inhibit advanced maturation of epiphyseal growth plate[5] giving a longer time for growth potential.…”

“…Combination therapy with GnRH analog (GnRHa) and rhGH causes a delay in the progression of BA and brings about more time for rhGH to insert its positive effect on bone growth, although the efficacy of this treatment for EP children has been questioned both in case of the poor impact on final height and also from the cost-benefit point of view. [58]…”

A Combination of Metformin and Insulin Is an Effective Treatment That Benefits the Cardiovascular and Cerebrovascular System in Individuals With Type 1 Diabetes Mellitus

“…The data extracted included the rst author, year of publication, country where the study was conducted, number of participants, number of patients lost to follow-up, mean age of participants, diabetes duration, intervention duration, clinical outcomes, and safety outcomes. Studies were excluded if they were case reports, letters, comments, or editorials or if no quantitative outcomes were reported 15 . The primary clinical outcomes of interest were cIMT 9 , reactive hyperemia index (RHI) 16 , ow-mediated dilation (FMD) 17 , pulse wave velocity (PWV) 18 , wall shear stress (WSS) 19 , and glucose infusion rate/insulin (M/I) 20 .…”