针刺联合知柏地黄汤化裁方治疗月经初潮后Tanner4期性早熟的疗效观察

岳上赛; 金玉晶; 赵帅; 孙凤平

doi:10.13748/j.cnki.issn1007-7693.20261360

针刺联合知柏地黄汤化裁方治疗月经初潮后Tanner4期性早熟的疗效观察

Observation of the Efficacy of Acupuncture Combined with Modified Zhizhi Dihuang Decoction in Treating Tanner Stage 4PrecociousPuberty after Menarche

摘要

摘要:
目的评价针刺联合知柏地黄汤化裁方治疗月经初潮后半年内Tanner4期性早熟女童(idiopathic precocious puberty，ICPP)的临床疗效及探讨其可能的作用机制。
方法收集河南省儿童医院自2024年1月—2025年1月收治的月经初潮后半年内Tanner4期ICPP女性患儿共60例，按随机信封法分为观察组和对照组各30例。观察组给予针刺联合知柏地黄汤化裁方治疗(每日1剂，分2次口服)，对照组给予醋酸曲普瑞林肌肉注射(50 μg·kg⁻¹ , 28d 1次)，治疗周期6月。观察2组治疗前后身高(height，H)、体质量(weight，W)、骨龄(bone age，BA)、身高增长量(△H)、体质量增加量(△W)、骨龄进展量(△BA)、乳腺体积(breast volume，BV)、最大卵泡直径(maximum follicle diameter，MFD)、子宫体积(uterus volume，UV)、卵巢容积(ovarian volume，OV)、月经来潮的变化情况以及检测2组血清黄体生成素(luteinizing hormone，LH)、雌二醇(estradiol，E2)、卵泡刺激素(follicle stimulating hormone，FSH)、胰岛素样生长因子-1(insulin-like growth factor-1，IGF-1) 、抗谬勒氏管激素(anti-mullerian hormone，AMH)、亲吻素-1(kisspeptin-1，KISS-1)、G蛋白偶联受体54(G protein-coupled receptor 54，GPR54)的水平。
结果 2种方案均能有效抑制Tanner4期性早熟女童骨龄进展，组间比较差异无统计学意义，但治疗后观察组患儿的身高增长显著高于对照组，而体质量增长显著低于对照组，差异均有统计学意义(P<0.01)；2组患儿治疗后血清性激素水平均明显下降，差异有统计学意义(P<0.01)，治疗后与对照组比较，观察组LH明显降低，IGF-1明显升高，差异有统计学意义(P<0.01)；与治疗前相比，治疗后2组患儿UV、LBV，RBV，LMFD和RMFD差异均无统计学意义；治疗后组间比较显示，观察组与对照组在UV、LBV，RBV，左最大卵泡直径(left maximum follicle diameter，LMFD)和右最大卵泡直径(right maximum follicle diameter，RMFD)指标方面差异均无统计学意义；观察组临床有效率(抑制骨龄进展、促进身高增长、抑制性激素水平)优于对照组(P<0.01)，安全性(抑制体质量过快增长、糖脂代谢)方面优于对照组(P<0.01)；与治疗前比较，2组患儿血清KISS-1、GPR54 、AMH水平均显著降低，差异有统计学意义(P<0.01)。
结论对于月经初潮后半年内Tanner4期性早熟女童，针刺联合知柏地黄汤化裁方治疗在骨龄抑制效果与GnRHα相当的前提下，在促进身高增长、控制体质量、调节IGF-1与LH水平及维持糖脂代谢安全性方面展现出综合优势，可为该类患儿的治疗提供临床参考，有待多中心、大样本、长期随访进一步验证，其作用机制可能与抑制KISS-1/GPR54信号通路相关。

Abstract:
OBJECTIVE To evaluate the clinical efficacy of acupuncture combined with modified Zhibai Dihuang Decoction in treating girls with Tanner stage 4 idiopathic precocious puberty(ICPP) within six months after menarche and to explore its possible mechanisms of action.
METHODS A total of 60 female children with Tanner stage 4 ICPP within six months after menarche, admitted to Henan Children’s Hospital from January 2024 to January 2025, were collected and randomly divided into an observation group and a control group, with 30 cases in each group. The observation group received acupuncture combined with modified Zhibai Dihuang Decoction(1 dose/day, taken orally in two doses), while the control group received intramuscular injections of triptorelin acetate(50 µg·kg⁻¹, once every 28 days), with a treatment period of six months. Height(H), weight(W), bone age(BA), height increase(△H), weight gain(△W), bone age progression(△BA), breast volume(BV), maximum follicle diameter(MFD), uterus volume(UV), ovarian volume(OV), changes in menarche and serum levels of luteinizing hormone(LH), estradiol(E2), follicle-stimulating hormone(FSH), insulin-like growth factor-1(IGF-1), anti-mullerian hormone(AMH), kisspeptin-1(Kiss-1), and G protein-coupled receptor 54(GPR54) were observed before and after treatment in both groups.
RESULTS Both treatments effectively inhibited bone age progression in girls with Tanner stage 4 ICPP, with no statistically significant difference between groups. However, after treatment, height growth in the observation group was significantly higher than that in the control group, while weight gain was significantly lower, with statistically significant differences(P<0.01); serum sex hormone levels in both groups were significantly reduced after treatment, with statistically significant differences(P<0.01). Compared with the control group after treatment, LH was significantly reduced and IGF-1 was significantly increased in the observation group, with statistically significant differences(P<0.01); compared with before treatment, there were no statistically significant differences in UV, LBV, RBV, LMFD and RMFD between the two groups after treatment; post-treatment comparison between groups showed no statistically significant differences in UV, LBV, RBV, LMFD and RMFD between the observation group and the control group; the clinical efficacy(inhibiting bone age progression, promoting height growth, inhibiting sex hormone levels) of the observation group was superior to that of the control group(P<0.01), and the safety profile(controlling rapid weight gain, glucose and lipid metabolism) was better than that of the control group(P<0.01); compared with before treatment, serum levels of KiSS-1, GPR54 and AMH in both groups were significantly reduced, with statistically significant differences(P<0.01).
CONCLUSION For girls with precocious puberty at Tanner stage 4 within six months of menarche, acupuncture combined with modified Zhibai Dihuang decoction treatment shows comparable bone age inhibition to GnRHα while demonstrating overall advantages in promoting height growth, controlling weight, regulating IGF-1 and LH levels, and maintaining safety in glucose and lipid metabolism. This provides clinical reference for the treatment of such patients, pending further verification through multi-centre, large-sample, long-term follow-up studies. Its mechanism may be related to the inhibition of the KISS-1/GPR54 signalling pathway.

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