联合应用促性腺激素释放激素类似物和生长激素治疗女童特发性中枢性性早熟的疗效观察

中国儿童保健杂志 ›› 2012, Vol. 20 ›› Issue (8): 731-734.

联合应用促性腺激素释放激素类似物和生长激素治疗女童特发性中枢性性早熟的疗效观察

孙小妹¹,吴瑾¹,杨凡¹,李嫔²,王秀敏³

1 四川大学华西第二医院儿科,四川成都 610041;
2 上海儿童医院,上海 200040;
3 浙江大学医学院附属儿童医院,浙江杭州 310003

收稿日期:2012-03-20 发布日期:2012-08-06 出版日期:2012-08-06
通讯作者: 杨凡,E-mail:fanfan1970sc@yahoo.com.cn
作者简介:孙小妹(1979-),女,山东人,主治医师,博士学位,主要研究方向为小儿内分泌疾病

Effects of treatment on female idiopathic central precious puberty with gonodotrophine-releasing hormone analogue and growth hormone

SUN Xiao-mei¹,WU Jin¹,YANG Fan¹,LI Pin²,WANG Xiu-min³

1 West China Second University Hospital of Sichuan University,Chengdu,Sichuan 610041,China;
2 Children's Hospital of Shanghai,Shanghai 200040,China;
3 Children's Hospital of Zhejiang University,Hangzhou,Zhejiang 310003,China

Received:2012-03-20 Online:2012-08-06 Published:2012-08-06

摘要/Abstract

摘要： 【目的】评价促性腺激素释放激素类似物(GnRHa)联合生长激素(GH)治疗女童特发性中枢性性早熟(ICPP)的疗效。【方法】对生长速率(GV)减慢至可能损害预测成年身高(PAH)的60例ICPP女童采用GnRHa和GH联合治疗6个月。行LH释放激素(LHRH)激发试验和GH激发试验,所有患者均不缺乏GH。观察治疗前后第二性征和GV的变化,观测子宫大小、卵巢容积、骨龄与年龄比值(BA/CA)的变化,并评估预测成人身高。【结果】经治疗后第二性征的发育明显受到抑制,表现为乳房回缩、子宫、卵巢容积减小。LHRH激发试验显示LH、FSH峰值显著降低,骨龄成熟延缓。按BA的身高标准差分值(HtSDSBA)从治疗前1.91±0.33升至1.44±0.27(P<0.001)。按CA的身高标准差分值(HtSDSCA)从0.31±0.12 下降至0.38±0.15。PAH由(153.4±1.1)cm升高到(156.0±1.0)cm(P<0.001)。GV由(3.81±1.3)cm增加至(8.63±3.5)cm。【结论】联合应用GnRHa和GH治疗ICPP,尤其是PAH明显落后的ICPP患者,能够有效抑制性腺轴及性腺发育,延缓骨龄成熟,改善预测成人终身高。

关键词: 特发性中枢性性早熟, 促性腺激素释放激素类似物, 生长激素, 预测成人身高

Abstract: 【Objective】 To assess the impact of treatment with Gonadotropin-releasing hormone (GnRH) analogs in combination with growth hormone(GH) in girls with idiopathic central precocious puberty (ICPP). 【Methods】 60 girls with ICPP whose growth velocity (GV) was so slowly that it impaired predicted adult height (PAH) were treated with recombinant human GH and GnRHa for 6 months.No patient showed classical GH deficiency.Before and after treatment,height,GV,and pubertal stage were observed,pelvic ultrasonic examination and X-ray bone age(BA) were detected,PAH was evaluated,and LH-releasing hormone (LHRH) stimulation test and GH stimulation test were performed. 【Results】 The secondary sexual development was regressed with interruption of their menses,reduction of the size of uterus,ovaries and breasts.Plasma FSH and LH peaks after the LHRH test were suppressed.The decreased ratio of BA/CA (chronology age) showed the disrupted maturation of BA.PAH increased from (153.4±1.1)cm to (156.0±1.0)cm (P<0.001) after 6 month treatment.The height SDS for BA (HtSDSBA) improved from 1.91±0.33 to 1.44±0.27(P<0.001),while height SDS for CA (HtSDSCA) from 0.31±0.12 to 0.38±0.15. 【Conclusion】 In gilrs with ICPP especially who have a very short PAH,combination of GnRHa and GH effectively inhibits the gonadal axis and delays bone maturation,improve the predicted adult height.

Key words: idiopathic central precocious puberty, gonadotropin-releasing hormone analogs, growth hormone, predicted adult height

中图分类号:

R725.8

孙小妹,吴瑾,杨凡,李嫔,王秀敏. 联合应用促性腺激素释放激素类似物和生长激素治疗女童特发性中枢性性早熟的疗效观察[J]. 中国儿童保健杂志, 2012, 20(8): 731-734.

SUN Xiao-mei,WU Jin,YANG Fan,LI Pin,WANG Xiu-min. Effects of treatment on female idiopathic central precious puberty with gonodotrophine-releasing hormone analogue and growth hormone[J]. journal1, 2012, 20(8): 731-734.

参考文献

[1] Carel JC,Lahlou N,Roger M,et al.Precocious puberty and statural growth[J].Human Reproduction Update,2004,10(2):135-147.
[2] Oerter KE,Manasco P,Barnes KM,et al.Adult height in precocious puberty after long-term treatment with deslorelin[J].J Clin Endocrinol Metab,1991,73:1235-1240.
[3] Brauner R,Adan L,Malandry F,et al.Adult height in girls with idiopathic true precocious puberty[J].J Clin Endocrinol Metab,1994,79:415- 420.
[4] Kletter GB,Kelch RP.Effects of gonadotropin-releasing hormone analog therapy on adult stature in precocious puberty[J].J Clin Endocrinol Metab,1994,79:331-334.
[5] Saggese G,Bertelloni S,Baroncelli GI,et al.Growth velocity and serum aminoterminal propeptide of type III procollagen in precocious puberty during gonadotropin-releasing hormone analogue treatment[J].Acta Paediatr,1993,82:261-266.
[6] Saggese G,Pasquino AM,Bertelloni S,et al.Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis[J].Acta Paediatr,1995,84:299 -304.
[7] Pasquino AM,Municchi G,Pucarelli I,et al.Combined treatment with gonadotropin-releasing hormone analog and growth hormone in central precocious puberty[J].J Clin Endocrinol Metab,1996,81:948 -951.
[8] Walvoord EC,Pescovitz OH.Combined use of growth hormone and with gonadotropin-releasing hormone analogues in precocious puberty:theoretic and practical considerations[J].Pediatrics,1999,104:1010-1014.
[9] Pucarelli I,Segni M,Ortore M,et al.Combined therapy with GnRH analog plus growth hormone in central precocious puberty[J].J Pediatr Endocrinol Metab,2000,13 (S):811-820.
[10] Kaplan SL,Grumbach MM.Pathophysiology and treatment of sexual precocity[J].J Clin Endocrinol Metab,1990,71:785-789.
[11] Pasquino AM,Pucarelli I,Accardo F,et al.Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogs:impact on adult height,body mass index,bone mineral content,and reproductive function[J].J Clin Endocrinol Metab,2008,93(1):190-195.
[12] 中华医学会儿科学分会内分泌遗传代谢学组.中枢性(真性)性早熟诊治指南[J].中华儿科杂志,2007,45(6):426-427.
[13] Lawson ML,Cohen N.A Single sample subcutaneous luteinizing hormone (LH)-releasing hormone (LHRH) stimulation test for monitoring LH uppression in children with central precocious puberty receiving sLHRH agonists[J].The Journal of Clinical Endocrinology & Metabolism,1999,84(12):4536-4540.
[14] Toumba M,Bacopoulou I,Savva SC,et al.Efficacy of combined treatment with growth hormone and gonadotropin releasing hormone analogue in children with poor prognosis of adult height[J].Indian Pediatrics,2007,44:497-502.
[15] Tatò L,Saggese G,Cavallo L,et al.Use of combined Gn-RH agonist and hGH therapy for better attaining the goals in precocious puberty treatment[J].Horm Res,1995,44(S3):49-54.
[16] Pasquino AM,Municchi G,Pucarelli I,et al.Combined treatment with gonadotropin- releasing hormone analogue and growth hormone in central precocious puberty[J].J Clin Endocrinol Metab,1996,81:948-951.
[17] Pasquino AM,Pucarelli I,Segni M,et al.Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone analogues and growth hormone[J].J Clin Endocrinol Metab,1999,84(2):449-452.
[18] Balducci R,Toscano V,Mangiantini A,et al.Adult height in short normal adolescent girls treated with gonadotropin-releasing hormone analog and growth hormone[J].J Clin Endocrinol Metab,1995,80:3596 -3600.
[19] Lanes R,Gunczler P.Final height after combined growth hormone and gonadotropinreleasing analogue treatment in short healthy children entering into normally timed puberty[J].Clin Endocrinol (Oxf),1998,49(2):197-202.