目的 探讨六味地黄丸联合醋酸亮丙瑞林治疗女童中枢性性早熟的临床疗效。方法 选取2021年3月—2022年5月北京市通州区妇幼保健院收治的120例中枢性性早熟女童，按随机数字表法将所有患者分为对照组和治疗组，每组各60例。对照组给予注射用醋酸亮丙瑞林微球，3.75 mg/次，1次/4周，以附带的注射液溶剂将药物充分混悬后皮下注射。治疗组在对照组治疗基础上口服六味地黄丸，体质量15～20 kg者，3 g/次；体质量21～25 kg者，4 g/次；体质量＞25 kg者，6 g/次；均为2次/d。两组疗程均为6个月。观察两组的临床疗效，比较治疗前后两组生长发育指标[骨龄差值（ΔBA）/年龄差值（ΔCA）、生长速率（GV）]，超声检查相关参数，儿少心理健康量表（MHS-CA）、儿少主观生活质量问卷（ISLQ）评分，以及血清促黄体生成素（LH）、卵泡刺激素（FSH）、胰岛素样生长因子1（IGF-1）、Ｉ型原胶原Ｎ-端前肽（P1NP）水平。统计两组不良反应情况。结果 治疗后，治疗组总有效率是88.33%，显著高于对照组的73.33%（P＜0.05）。治疗后，两组ΔBA/ΔCA、GV均较治疗前显著降低（P＜0.05），且以治疗组降低更明显（P＜0.05）。治疗后，两组乳房直径、子宫容积、卵巢容积、最大卵泡直径均较治疗前显著减小（P＜0.05），以治疗组减小更显著（P＜0.05）。治疗后，两组MHS-CA、ISLQ评分均较治疗前显著增加（P＜0.05），且治疗后，治疗组MHS-CA、ISLQ评分均显著高于对照组（P＜0.05）。治疗后，两组血清LH、FSH、IGF-1、P1NP水平均显著降低（P＜0.05）；治疗后，治疗组LH、FSH、IGF-1、P1NP水平显著低于对照组（P＜0.05）。治疗后，治疗组和对照组不良反应发生率分别是6.67%、5.00%，两组比较差异无统计学意义。结论 六味地黄丸联合醋酸亮丙瑞林治疗女童中枢性性早熟安全性较好，疗效确切，能有效减慢患儿骨龄成熟和生长速度，抑制生殖系统过早发育，改善心理健康和生活质量，进一步调节机体性激素水平和骨代谢。

Objective To explore the clinical effect of Liuwei Dihuang Pills combined with leuprorelin acetate in treatment of central precocious puberty in girls. Methods A total of 120 girls with central precocious puberty admitted to Tongzhou District Maternal and Child Health Hospital of Beijing from March 2021 to May 2022 were selected and divided into control group and treatment group by random number table method, with 60 cases in each group. Patients in the control group were given Leuprorelin Acetate Microspheres for injection, 3.75 mg/time, once/4 weeks, the drug was fully suspended and injected subcutaneously with the included injection solvent. Patients in the treatment group were po administered with Liuwei Dihuang Pills, body weight of 15 — 20 kg, 3 g/time, body weight of 21 — 25 kg, 4 g/time, body weight > 25 kg, 6 g/time, twice daily. The treatment course of both groups was 6 months. The clinical efficacy of the two groups was observed, and the growth and development indicators [ΔBA/Age difference (ΔCA), growth rate (GV)], ultrasonic-related parameters, adolescent Mental Health Scale (MHS-CA) and Subjective Quality of Life Questionnaire (ISLQ) scores, and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), insulin-like growth factor 1 (IGF-1), and type I procollagen N-terminal propeptide (P1NP) in the two groups were compared before and after treatment. The adverse reactions of the two groups were analyzed. Results After treatment, the total effective rate of the treatment group was 88.33%, which was significantly higher than that of the control group (73.33%, P < 0.05). After treatment, ΔBA/ΔCA and GV in two groups were significantly decreased compared with before treatment (P < 0.05), and the decrease was more obvious in the treatment group (P < 0.05). After treatment, breast diameter, uterine volume, ovarian volume and maximum follicle diameter in two groups were significantly decreased compared with before treatment (P < 0.05), and the decrease was more significant in the treatment group (P < 0.05). After treatment, the MHS-CA and ISLQ scores of the two groups were significantly increased compared with before treatment (P < 0.05), and after treatment, the MHS-CA and ISLQ scores of the two groups were significantly higher than those of the control group (P < 0.05). After treatment, serum levels of LH, FSH, IGF-1 and P1NP in two groups were significantly decreased (P < 0.05). After treatment, the levels of LH, FSH, IGF-1 and P1NP in the treatment group were significantly lower than those in the control group (P < 0.05). After treatment, the incidence of adverse reactions in the treatment group and the control group was 6.67% and 5.00%, respectively, and there was no statistical significance between the two groups. Conclusion Liuwei Dihuang Pills combined with leuprorelin acetate is safe and effective in the treatment of central precocious puberty in girls, and can effectively slow down the bone age maturity and growth rate of children, inhibit the premature development of reproductive system, improve mental health and quality of life, which can further regulate the level of sex hormone and bone metabolism.

R985

北京市通州区科技计划项目（KJ2022CX051）