Long‐term efficacy and safety of gonadotropin‐releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta‐analysis

Abstract

Objective To investigate the long‐term efficacy and safety of gonadotropin‐releasing hormone analog (GnRHa) treatment in children with idiopathic central precocious puberty (CPP). Method The protocol was registered with International Prospective Register of Systematic Reviews (CRD42018102792). PubMed, EMBASE and the Cochrane Library were searched for eligible comparative and single‐arm studies. Results We identified a total of 98 studies that included 5475 individuals. The overall risk of bias of the eligible studies ranged from critical to moderate. The overall quality of evidence for each outcome ranged from very low to moderate. Evidence‐based comparative studies showed that GnRHa treatment increase final adult height (FAH, cm; studies = 4, n = 242; mean difference [MD] = 4.83; 95% confidence interval [CI], 2.32 to 7.34; I2 = 49%) and decrease body mass index (BMI, kg/m2; studies = 3, n = 334; MD = −1.01; 95% CI, −1.64 to −0.37; I2 = 0%) in girls with idiopathic CPP compared with no treatment. The incidence of polycystic ovary syndrome (PCOS) did not significantly differ with and without GnRHa treatment (studies = 3, n = 179; risk ratio = 1.21; 95% CI, 0.46 to 3.15; I2 = 48%). The evidence for other long‐term outcomes was very weak to deduce the effects of GnRHa treatment. Further, limited evidence is available on its effects in boys. Conclusion Compared with no treatment, evidence indicates that GnRHa treatment increase FAH and decrease BMI in girls with idiopathic CPP. GnRHa treatment did not evidently increase the risk of PCOS. However, evidence regarding other key long‐term outcomes (such as infertility and malignant or metabolic diseases) was considered very weak to suggest the benefits or side effects of GnRHa treatment. Additional high‐quality evidence is needed before firm conclusions can be drawn.

Preventive Effect of Anemarrhenae rhizome and Phellodendri cortex on Danazol-Induced in Precocious Puberty in Female Rats and Network Pharmacological Analysis of Active Compounds

“…Until now, gonadotrophin-releasing hormone analog (GnRHa) is the only effective treatment for CPP among the currently available, which maintains the stable level of GnRH to reduce the steroid hormones to the prepubertal level. Several synthetic peptide drugs, such as leuprolide, triptorelin, and goserelin, have been used clinically [ 6 , 7 ]. GnRHa continuously stimulates the anterior pituitary through GnRH receptors.…”

“…However, various common side effects of GnRHa have been reported, such as injection site reactions, sterile abscess, pain, bruising, and nausea [ 10 ]. In addition, there are no clear evidence of the effect of GnRHa treatment on increasing the adult height of girls with CPP aged between 6 and 8 years [ 7 , 8 ].…”

Central Precocious Puberty in Boys and Girls: Similarities and Differences

“…Long-term results demonstrated improvements of adult height in both boys and girls. A recent systematic review and meta-analysis (98 studies, 5475 individuals) concluded that GnRH analog treatment increase adult height and decrease the body mass index in girls with idiopathic CPP in comparison with no treatment [79]. The same authors stated that GnRH analog treatment did not evidently increase the risk of PCOS [79].…”

“…A recent systematic review and meta-analysis (98 studies, 5475 individuals) concluded that GnRH analog treatment increase adult height and decrease the body mass index in girls with idiopathic CPP in comparison with no treatment [79]. The same authors stated that GnRH analog treatment did not evidently increase the risk of PCOS [79]. Even better outcome in terms of adult height seems to present in males, but few data are available and poor evidence on the reproductive function in adulthood are available in male sex [50,73,76].…”

“…Future longitudinal trials should explore these items. In addition, evidence regarding other key long-term outcomes (such as infertility and malignant or metabolic diseases) were judged to be very weak, suggesting high benefits and few side effects of GnRH analog treatment [79]. Finally, psychological difficulties related to precocious pubertal onset, presence of menarche in girls and aggressiveness in males represent the main issues for treatment [53], but sound data on these aspects are poorly evaluated, mainly in males.…”