GnRHa bolsters growth of girls with early puberty

Treatment with gonadotropin‐releasing hormone analog (GnRHa) helps boost the adult height lower the body mass index (BMI) of girls with idiopathic central precocious puberty (CCP), according to the results of a meta-analysis.

Compared with no treatment, GnRHa produced an increase of ≥2.32 cm in final adult height (FAH), bringing it closer to the target height, the researchers noted.

Furthermore, there was no increase in the risk of overweight or obesity and of polycystic ovary syndrome (PCOS), they added. In fact, BMI dropped by ≥0.28 kg/m² in girls who did versus did not receive GnRHa.

The meta-analysis included 98 studies involving 5,475 individuals. The risk of bias ranged from critical to moderate, while quality of evidence for each outcome varied between very low to moderate.

Based on pooled data from comparative studies comparing GnRHa exposure versus no treatment in girls with idiopathic CPP, the mean difference in FAH was 4.83 (95 percent confidence interval [CI], 2.32–7.34; I², 49 percent; four studies, n=242); that in BMI was –1.01 (95 percent CI, −1.64 to −0.37; I², 0 percent; three studies, n=334). [Clin Endocrinol 2021;doi:10.1111/cen.14410]

Meanwhile, the incidence of PCOS was similar in the two groups (three studies, n=179; risk ratio, 1.21, 95 percent CI, 0.46–3.15; I², 48 percent).

“Early evidence has indicated that precocious puberty may lead to certain psychological or social problems, which are considered to bother parents and may affect the clinical treatment of CPP,” the researchers noted. [Horm Res Paediatr 2019;91:357-372]

However, the present data indicate that GnRHa treatment did not aggravate the cognitive, psychological, and social problems of children with idiopathic CPP and had the potential to reduce problems in some children. [Front Psychol 2016;7:1053; Horm Res Paediatr 2017;88:347-353]

The findings are somewhat consistent with those of a previous systematic review that evaluated the long-term outcomes of GnRHa treatment in children with CPP. Specifically, it showed that GnRHa treatment helped improve FAH in girls with CPP and had no clear negative impact on BMI, risk of PCOS, or bone mass density. However, unlike the present meta-analysis, only the PubMed database was searched in the previous review. [Eur J Endocrinol 2016;174:R79-R87]

The researchers also acknowledged that the data for other long‐term outcomes were not enough to deduce the effects of GnRHa treatment. “Further, limited evidence is available on its effects in boys.”

A synthetic peptide drug modelled based on human hypothalamic GnRH, GnRHa interacts with its corresponding receptor and stimulates the synthesis and secretion of follicle-stimulating hormone and luteinizing hormone in the initial phase of administration (‘flare up’). It has been used for treating CPP, and its effects on hypothalamic–pituitary–gonadal axis suppression has been generally recognized. However, the long-term efficacy and safety remain unclear, and reports to date are mixed. [Arch Endocrinol Metab 2016;60:163-172; Pediatrics 2009;123:e752-e762]