Influence of GnRHa on Long-Term Outcomes in Idiopathic Central Precocious Puberty

Data from a systematic review and meta-analysis assessing nearly 100 studies with more than 5000 patients is detailing the long-term efficacy and safety of gonadotropin-releasing hormone analog (GnRHa) treatment in children with idiopathic central precocious puberty (CPP).

Although results of the study provide insight into the effects of GnRHa treatment, including its effects on final adult height (FAH), body mass index (BMI), and risk of polycystic ovary syndrome (PCOS), investigators point out the need for more high-quality studies assessing long-term outcomes of GnRHa treatment in children with CPP.

“In this systematic review, we aimed to determine the long-term efficacy and safety of GnRHa treatment in children with ICPP. Current evidence is mainly focused on girls with ICPP, and the overall quality of evidence for each studied outcome was found to range from very low to moderate,” wrote investigators.

Together with a team of colleagues from the Tongji Medical College, Xiaoping Luo, MB, professor and chairman of the department of pediatrics at the Tongji Hospital of Tongji Medical College, designed the current study as a systematic review and meta-analysis to provide clinicians with an overview of the long-term efficacy and safety of GnRHa treatment. With this in mind, investigators queried the PubMed, EMBASE, and Cochrane Library databases from inception through November 2019 to identify studies for inclusion in their systematic review and meta-analysis.

Investigators had 3 specific inclusion criteria for the study, which were that studies needed to be prospective or retrospective comparative studies and single-arm studies, studies needed to include participants with ICPP with the onset of secondary sex characteristics before 8 years of age in girls and before 9 years of age in boys, and studies need to report long-term outcomes in participants who received GnRHa compared with participants who received no treatment/placebo or GnRHa plus growth hormone.

The primary outcomes of interest for the study included FAH, target height (TH), BMI, and incidence of PCOS among girls and androgen excess among boys. Secondary outcomes of interest included menstrual parameters, growth velocity (GV), IGF-1 level, BMD, glucose and lipid metabolism, insulin resistance parameters, and psychological state.

Investigators identified a total of 98 studies enrolling a population of 5475 participants for possible inclusion in the current study. Of these 18 were randomized comparative studies and 81 were single-arm studies. The sample size of studies ranged from 6 to 33 and 98.5% of the total population were women.

Upon analysis, investigators determined the overall risk of bias among eligible studies ranged from critical to moderate and the overall quality of evidence for each outcome ranged from very low to moderate. When assessing evidence-based comparative studies, results indicated GnRHa treatment was associated with increased FAH (mean difference=4.83 cm [95% CI, 1.32 to 7.34]; I2=49%) and decreased BMI (MD=—1.01 [95%, -1.64 to -0.37]; I2=0%) in girls with idiopathic CPP compared with no treatment.

Additionally, incidence of PCOS did not appear to be significantly different with and without GnRHa therapy (RR, 1.21 [95% CI, 0.46 to 3.15]; I2=48%). Investigators pointed out evidence for other long-term outcomes were very weak and contributed to an inability to deduce effects of GnRHa treatment on these outcomes. Investigators also pointed out limited evidence prevents these results from being applicable to populations of boys with idiopathic CPP.

“The current evidence indicates that GnRHa treatment improve the FAH of girls with ICPP, thus allowing them to meet or exceed their TH. GnRHa treatment also reduce the BMI levels of participants compared with BMI of those treated with placebo,” wrote investigators. “Furthermore, GnRHa did not appear to increase the risk of PCOS. However, evidence regarding other predefined key outcomes, such as infertility, malignancy and metabolic diseases, is very weak to indicate the benefits or side effects of GnRHa treatment.”

This study, “Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta-analysis,” was published in Paediatric Endocrinology.