The Efficacy of GnRHa Alone or in Combination with rhGH for the Treatment of Chinese Children with Central Precocious Puberty

Abstract

The addition of recombinant human growth hormone (rhGH) to GnRH agonist (GnRHa) to treat central precocious puberty (CPP) is controversial. We systemically reviewed and evaluated the efficacy and safety of the rhGH and GnRHa adjunctive therapy in Chinese children with CPP and assessed the influence of age and therapy duration on the efficacy of the combined treatment. A total of 464 patients were included from 14 studies. Compared with baseline, administration of GnRHa plus rhGH led to a significant increase in height, predicted adult height (PAH) and height standard deviation for bone age (HtSDS-BA), corresponding to a weighted mean difference (WMD) (95%CI) of 9.06 cm (6.41, 11.70), 6.5 cm (4.47, 8.52), and 0.86 (0.58, 1.14) respectively. Subgroup analysis showed the combined therapy had increased efficacy in subjects with initial treatment age younger than 10 years old or with treatment lasting over 12 months. Compared with GnRHa alone treatment, the combined treatment led to a significant increase in height, PAH and HtSDS-BA, corresponding to a WMD (95% CI) of 3.56 cm (2.54, 4.57), 3.76 cm (3.19, 4.34) and 0.56 (0.43, 0.69). The combined treatment exhibited no safety concerns. Our findings may aid clinicians in making treatment decisions for children with CPP.

Comparative Efficacy and Safety of Three Current Clinical Treatments for Girls with Central Precocious Puberty: A Network Meta-Analysis

“…In addition to its inclusion of a total of 1,268 girls, another strength of this NMA was the specific inclusion criteria, complete search strategy, and eligibility assessed independently by two reviewers. Thirdly, Wang et al's (17) meta-analysis only analyzed 3 outcome measurements (height, PAH, and height standard deviation for bone age) with a total of 464 Chinese patients included from 14 studies, and Li et al's (18) meta-analysis included 8 studies with 309 girls and analyzed 2 endpoints (final height and standard deviation scores for final height). To provide a more complete clinical reference, we included 22 studies with 1,268 patients and 6 endpoints into analysis.…”

“…In some patients, the growth velocity decrease was so marked that predicted adult height (PAH) was impaired (16). Wang's meta-analysis included 14 studies composed of 7 observational studies and 7 case-control studies with a total of 464 Chinese patients (17). This study demonstrated that compared with GnRHa alone therapy, the addition of growth hormone (GH) to GnRHa treatment led to a marked increase in PAH, height, and height standard deviation for bone age, corresponding to a weighted mean difference (95% confidence interval [CI]) of 3.76 (3.19, 4.34) cm, 3.56 (2.54, 4.57) cm, and 0.56 (0.43, 0.69) cm, respectively (17).…”

“…Wang's meta-analysis included 14 studies composed of 7 observational studies and 7 case-control studies with a total of 464 Chinese patients (17). This study demonstrated that compared with GnRHa alone therapy, the addition of growth hormone (GH) to GnRHa treatment led to a marked increase in PAH, height, and height standard deviation for bone age, corresponding to a weighted mean difference (95% confidence interval [CI]) of 3.76 (3.19, 4.34) cm, 3.56 (2.54, 4.57) cm, and 0.56 (0.43, 0.69) cm, respectively (17). The results of a meta-analysis showed that GnRHa treatment may have a positive effect on the improvement of final height in girls with precocious puberty, while adding GH to the therapy may have more advantages (18).…”

Effects of Recombinant Human Growth Hormone on the Onset of Puberty, Leydig Cell Differentiation, Spermatogenesis and Hypothalamic KISS1 Expression in Immature Male Rats

“…These results demonstrate that in prepubertal male rats, rhGH accelerated the functional maturation of Leydig cells and increased testosterone synthesis, contributing to an early onset of puberty. In rhGH therapy for human children with short stature, effective dosages of rhGH are 0.08–0.13 IU/kg/d [ 24 25 ]. In peripubertal rat model study, administration of rhGH at 2–11 IU/kg/d increased body growth [ 18 19 ].…”

Should Skeletal Maturation Be Manipulated for Extra Height Gain?

“…Patients with a low growth velocity or no improvement in PAH during GnRHa benefitted most from the combination therapy ( 89 ) (LoE 2). A systematic review and meta-analysis reported an increase of PAH of 6.5 cm in CPP when treated with rhGH plus GnRHa, especially in those starting treatment before 10 years old, or with treatment lasting more than 12 months ( 90 ). Compared to GnRHa alone, the combined treatment showed a 3.7 cm higher PAH (LoE2).…”