Kisspeptin Levels in Girls with Precocious Puberty: A Systematic Review and Meta-Analysis

Abstract

<b><i>Background/Aims:</i></b> Kisspeptin (KP) is a key player in the regulation of the release of gonadotropin-releasing hormone (GnRH), which increases the secretion of gonadotropin during puberty to establish reproductive function and regulate the hypothalamic-pituitary-gonadal axis. Premature activation of GnRH secretion leads to idiopathic/central gonadotropin-dependent precocious puberty (CPP). We aimed to compare the blood KP concentrations in girls with CPP and healthy controls. <b><i>Methods:</i></b> A systematic review and meta-analysis was performed. We searched MEDLINE, EMBASE, The Cochrane Library, and SciELO. Random-effects model and standardized mean difference (SMD) were used. Heterogeneity was assessed through <i>I</i>². Meta-regression considered patient age, KP fraction, and analytical method for KP measurement. <b><i>Results:</i></b> The 11 studies included comprised 316 CPP patients and 251 controls. Higher KP levels in the CPP group were found (SMD 1.53; CI 95% = 0.56–2.51). Subgroup analysis revealed association with patient age (<i>p</i> = 0.048), indicating a positive correlation between elevation in KP concentration and age in CPP group. A group of patients with precocious thelarche (PT) from 5 of the included studies comprising 121 patients showed higher levels of KP (1.10; −0.25–2.45: CI 95%) and high heterogeneity (<i>I</i>² = 91%). The CPP/PT ratio for KP level indicates KP 36% higher on CPP than PT patients. <b><i>Conclusions:</i></b> A consistent difference in KP levels between girls with CPP and controls was identified. While there are important limitations in KP assays which argue against its use as a diagnostic tool, the KP levels in CPP versus control and PT children are consistent with the predicted mechanisms and pathophysiology of CPP.