补肾调肝中药辅助治疗对中枢性性早熟的疗效和骨代谢指标影响的Meta分析

Meta-analysis of Clinical Efficacy of Kidneys-tonifying and Liver-regulating Chinese Medicines in the Adjuvant Treatment of Central Precocious Puberty and Effect on Bone Metabolism Indexes

目的系统评价补肾调肝中药辅助治疗中枢性性早熟(Central precocious puberty,CPP)的疗效及对骨代谢指标的影响。方法计算机检索中国知网、万方数据知识服务平台、维普数据库、中国生物医学文献服务系统、PubMed、Embase、Cochrane Library所收录的补肾调肝类中药辅助治疗CPP的随机对照试验,检索时间为2014年1月1日至2024年1月31日。使用Review Manager 5.4.1软件和Stata 17.0进行统计学分析。结果共纳入16项符合标准的随机对照研究,共1528例患儿。Meta分析结果显示:与单独使用促性腺激素释放激素类似物(Gonadotropin releasing hormone agonist,GnRHa)比较,补肾调肝类中药联合GnRHa明显提高CPP患儿总有效率[OR=4.17,95%CI:2.97~5.84,P<0.00001],对性激素卵泡刺激素(Follicle-stimulating hormone,FSH)[SMD=-1.94,95%CI:-2.41~-1.47,P<0.00001]、黄体生成素(Luteinizing hormone,LH)[SMD=-1.56,95%CI:-2.17~-0.94,P<0.00001]、雌二醇(Estradiol,E_(2))[SMD=-1.40,95%CI:-1.91~-1.36,P<0.00001]及内生殖器发育指标子宫容积[MD=-0.82,95%CI:-1.01~-0.63,P<0.00001]、卵巢容积[MD=-0.29,95%CI:-0.40~-0.18,P<0.00001]、卵泡直径[MD=-0.77,95%CI:-0.95~-0.60,P<0.00001]以及骨龄指数[MD=-0.19,95%CI:-0.25~-0.12,P<0.00001]的抑制作用均优于单纯GnRHa治疗。补肾调肝类中药联合GnRHa对骨代谢指标Ⅰ型原胶原氨基端肽(Procollagen type 1 N-terminal propeptide,P1NP)[SMD=-0.71,95%CI:-0.90~-0.52,P<0.00001]、骨钙素N端中分子片段(Medium molecular fragment of osteocalcin N-terminal,N-MID)[SMD=-2.33,95%CI:-3.46~-1.20,P<0.0001]的抑制作用均优于单纯使用GnRHa治疗,且不会增加不良反应[OR=0.71,95%CI:0.42~1.23,P=0.22],临床使用较为安全。结论与单纯西药治疗比较,补肾调肝类中药辅助治疗CPP疗效更为显著。补肾调肝类中药辅助治疗能更好的抑制性发育,降低骨形成指标,抑制骨代谢,延缓骨成熟,临床使用较为安全。

Objective To systematically evaluate the efficacy of kidney-tonifying and liver-regulating Chinese medicines in the adjuvant treatment of central precocious puberty(CPP)and their effect on bone metabolism indexes.Methods Randomized controlled trials(RCTs)of kidney-tonifying and liver-regulating Chinese medicines for CPP published from January 1,2014,to January 31,2024,were searched from databases including CNKI,Wanfang Data,VIP,China Biomedical Literature Service System,PubMed,Embase,and Cochrane Library.Statistical analyses were conducted using Review Manager 5.4.1 and Stata 17.0.Results A total of 16 RCTs involving 1528 children met the inclusion criteria.Meta-analysis results indicated that compared to gonadotropin-releasing hormone agonist(GnRHa)alone,the combination of kidney-tonifying and liver-regulating Chinese medicines with GnRHa significantly increased the overall effective rate in CPP patients[OR=4.17,95%CI:2.97-5.84,P<0.00001],and showed superior inhibitory effects on follicle-stimulating hormone(FSH)[SMD=-1.94,95%CI:-2.41 to-1.47,P<0.00001],luteinizing hormone(LH)[SMD=-1.56,95%CI:-2.17 to-0.94,P<0.00001],estradiol(E_(2))[SMD=-1.40,95%CI:-1.91 to-1.36,P<0.00001],and indicators of internal reproductive organ development,such as uterine volume[MD=-0.82,95%CI:-1.01 to-0.63,P<0.00001],ovarian volume[MD=-0.29,95%CI:-0.40 to-0.18,P<0.00001],follicle diameter[MD=-0.77,95%CI:-0.95 to-0.60,P<0.00001],and bone age index[MD=-0.19,95%CI:-0.25 to-0.12,P<0.00001].Additionally,the combination therapy demonstrated superior inhibitory effects on bone metabolism indexes such as procollagen type 1 N-terminal propeptide(P1NP)[SMD=-0.71,95%CI:-0.90 to-0.52,P<0.00001]and medium molecular fragment of osteocalcin N-terminal(N-MID)[SMD=-2.33,95%CI:-3.46 to-1.20,P<0.0001].Importantly,the combination treatment did not increase adverse reactions[OR=0.71,95%CI:0.42-1.23,P=0.22],indicating a relatively safe clinical use.Conclusion Compared to conventional Western drug treatment,kidney-tonifying and liver-regulating Chinese medicines provide significantly better efficacy in the adjuvant treatment of CPP.This approach effectively inhibits sexual development,reduces bone formation indexes,suppresses bone metabolism,and delays skeletal maturation,with a safety profile suitable for clinical application.