Syndrome differentiation and treatment of pediatric central precocious puberty: role of the spleen-kidney axis
Abstract
Pediatric central precocious puberty (CPP) is driven by premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, along with immune-inflammatory imbalance, metabolic dysfunction, obesity, and gut microbiota-derived signals. According to traditional Chinese medicine (TCM) principles, kidney yin deficiency with hyperactive ministerial fire and spleen deficiency with phlegm-dampness form the basis for central pubertal activation and peripheral metabolic-inflammatory burden, thus supporting a combined approach for obesity-related or mixed-pattern CPP. Representative prescriptions include modified Zhibai Dihuang pills with Liujunzi decoction and modified Danzhi Xiaoyao powder with Erchen decoction, which integrate kidney yin-nourishment and ministerial fire-clearance with spleen qi-strengthening and phlegm resolution. Available clinical evidence suggests potential benefits in controlling secondary sexual characteristics, reducing gonadotropin and sex-steroid levels, and slowing bone-age advancement. Mechanistic studies indicate possible regulation of kisspeptin/GPR54/GnRH and LH/FSH-sex-steroid signaling, Th1/Th2/Treg homeostasis, NF-κB/NLRP3 pathways, adipokine imbalance, insulin resistance, hypothalamic inflammation, and gut microbiota-associated metabolism. However, most mechanistic links remain indirect, comparative trials are scarce, and direct correction of pathogenic MKRN3 or DLK1 variants has not been demonstrated. In this review, we have discussed the role…
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