滋阴泻火方联合甲地孕酮治疗快进展型性早熟女童61例随机对照研究

Treatment of 61 Rapid Progressive Central Precocious Puberty Girls with Combined Therapy of Ziyin Xiehuo Formula(滋阴泻火方)and Megestrol:A Randomized Controlled Trial

目的观察滋阴泻火方联合甲地孕酮治疗快进展型性早熟女童的临床疗效。方法130例快进展型性早熟女童随机分为治疗组和对照组各65例。治疗组予口服滋阴泻火方中药颗粒剂(每次30 g、每日2次)联合甲地孕酮片(每日6或8 mg、分为3次),对照组予皮下注射促性腺激素释放激素拟似剂(GnRHa)注射用醋酸亮丙瑞林微球(初次剂量为3.75 mg,4周后根据患儿体重以80μg/kg的剂量每4周皮下注射1次),疗程为6个月。比较两组治疗前后乳核直径及乳核缩小患儿比例、中医证候积分、子宫及卵巢容积、卵泡直径、身高及骨龄变化、生长速率、体重指数,并监测肝肾功能及不良反应的发生以评估其安全性。结果最终纳入123例患儿进行分析,其中治疗组61例、对照组62例。治疗后治疗组有52例(85.25%)患儿乳核缩小,对照组有54例(87.10%),两组乳核缩小患儿比例差异无统计学意义(P>0.05)。与本组治疗前比较,两组治疗后乳核直径和卵泡直径缩小,骨龄、身高及体重指数均增加(P<0.05或P<0.01);治疗组治疗后中医证候积分降低,对照组治疗后子宫及卵巢容积缩小(P<0.01)。治疗后两组间比较,治疗组中医证候积分低于对照组,而子宫、卵巢容积及卵泡直径、生长速率高于对照组(P<0.01)。两组患儿均未发生严重不良反应。结论滋阴泻火方联合甲地孕酮治疗快进展型性早熟女童可抑制乳核发育,延缓子宫及卵巢发育进程,抑制骨龄超前趋势,且不会造成明显的生长减速。

Objective To observe the therapeutic effect of combined therapy of Ziyin Xiehuo Formula(滋阴泻火方,ZXF)and megestrol in the treatment of girls with rapid progressive central precocious puberty.Methods A total of 130 girls with rapid progressive central precocious puberty were randomized into the treatment group(65 cases)and control group(65 cases).ZXF granules(30 g per time,twice daily)and megestrol tablets(6 or 8 mg per day with three times)were administered orally in the treatment group,while subcutaneous injection of hormone-releasing hormone analogue(GnRHa)and leuprolide acetate microspheres injection(the initial dose was 3.75 mg for 4 weeks,then the dose was determined based on the weight as to 80μg/kg,once every 4 weeks)were given to the control group,both for 6 months.The mammary nucleus diameter and the proportion of children with nucleus that retract,traditional Chinese medicine(TCM)syndrome scores,size of uterus and ovary,follicle diameter,height and X-ray bone age,growth rate and body mass were observed before and after treatment in both groups.And the liver and kidney function and adverse reactions were assessed to evaluate the safety.Results Finally,123 cases including 61 cases in the treatment group and 62 cases in the control group were included in the analysis.At 6-month treatment,there were 52 children(85.25%)with mammary nucleus that retract in the treatment group and 54 children(87.10%)in the control group,with no significant difference(P>0.05).The mammary nucleus diameter and follicle diameter reduced,the bone age,height,and body mass significantly increased in both groups after treatment(P<0.05 or P<0.01);TCM syndrome scores significantly decreased in the treatment group,and the sizes of uterus and ovary were reduced in the control group after treatment(P<0.O1).Compared to those in the control group,TCM syndrome scores were lower,while the sizes of uterus and ovary were greater,follicle diameter and growth rate were higher in the treatment group(P<0.01).No serious adverse reactions occurred.Conclusion In the treatment of girls with rapid progressive central precocious puberty,zXF combined with megestrol can inhibit the growth of mammary nucleus,delay the development of uterus and ovary,inhibit the advanced trend of bone age and will not cause significant height growth deceleration.