Botanical drug preparations and related East Asian medicine interventions for central and idiopathic central precocious puberty: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND

Central precocious puberty (CPP), particularly idiopathic CPP (ICPP), is characterized by the premature activation of the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone agonists (GnRHas) are established biomedical treatments, but treatment burden, cost, and incomplete long-term outcome data have encouraged interest in adjunctive botanical drug preparations used in East Asian medicine. However, these preparations differ substantially in composition, dose, comparator, and reporting quality.

OBJECTIVES

The aim of this study is to synthesize systematic reviews (SRs) and meta-analyses (MAs) evaluating botanical drug preparations and related East Asian medicine interventions for CPP/ICPP, appraise methodological quality and certainty, quantify the overlap of primary trials, and identify evidence gaps.

METHODS

Eligible studies included systematic reviews/meta-analyses of randomized trials in children with CPP/ICPP. Databases were searched from inception to September 2025. Evidence was narratively synthesized by formulation family, comparator, and outcome. Review quality was assessed using AMSTAR-2, risk of bias using ROBIS, certainty using GRADE domains where feasible, and primary-trial overlap using the corrected covered area.

RESULTS

Four systematic reviews/meta-analyses were included. Favorable signals were reported mainly for Zhibai Dihuang-based preparations, Dabuyin-based preparations, Nourishing Yin-Purging Fire regimens, and botanical drug preparations combined with GnRHas. Outcomes included clinical response, uterine/ovarian volume, gonadotropin levels, estradiol levels, and bone age index. However, interpretation was limited by heterogeneous formulations, variable comparators, an unclear or high risk of bias in the primary trials, incomplete formulation reporting, possible publication/language bias, and overlap of primary studies. Adverse events were incompletely defined and may have been under-reported; long-term pediatric safety was rarely assessed.

CONCLUSION

Current evidence suggests a possible adjunctive benefit of selected botanical drug preparations, particularly in combination with GnRHas, for CPP/ICPP. However, the certainty of the evidence remains low because of methodological weaknesses, heterogeneous interventions, single-country evidence, incomplete safety reporting, and limited long-term outcome data. High-quality multicenter trials with standardized botanical authentication, dosing, outcome definitions, adverse-event surveillance, and long-term follow-up are needed before routine clinical integration can be recommended.