中枢性性早熟对儿童体格及性发育的影响

赵兰; 钟燕

doi:10.7499/j.issn.1008-8830.2014.05.024

PDF(1487 KB)

HTML

中国当代儿科杂志 ›› 2014, Vol. 16 ›› Issue (5) : 555-559. DOI: 10.7499/j.issn.1008-8830.2014.05.024

综述

中枢性性早熟对儿童体格及性发育的影响

赵兰, 钟燕

作者信息 +

Effects of central precocious puberty on physical and sexual development in children

ZHAO Lan, ZHONG Yan

Author information +

文章历史 +

摘要

中枢性性早熟（CPP）是一种青春期发育异常，表现为第二性征提前、骨格成熟和体格提前发育，最终影响儿童的成年身高，甚至可能会产生如恐惧、不安等心理行为问题。目前国际上公认治疗最好的药物为促性腺激素释放激素类似物（GnRHa），其主要目的是改善儿童的最终成年身高；但与此同时，其对患儿的生长发育也存在一些不良反应。该文就CPP及GnRHa治疗对儿童体格及性发育的影响作一综述，以引起临床医师对此疾病及其安全用药的关注。

Abstract

As abnormal pubertal development, central precocious puberty (CPP) is manifested by the secondary sexual characteristics, skeletal maturation, and physical development in advance. It ultimately affects the adult height of children, even producing some psychological and behavioral problems such as fear and anxiety. Currently, gonadotropin releasing hormone analogue (GnRHa) is recognized as the best medicine worldwide for treating CPP in order to increase children’s final adult height; however, it has some adverse effects on the growth and development of children. This paper reviews the effects of CPP and GnRHa on children's physical and sexual development, with the aim of increasing physicians awareness of this disease and the safety of medication.

导出引用

赵兰, 钟燕. 中枢性性早熟对儿童体格及性发育的影响[J]. 中国当代儿科杂志. 2014, 16(5): 555-559 https://doi.org/10.7499/j.issn.1008-8830.2014.05.024

ZHAO Lan, ZHONG Yan. Effects of central precocious puberty on physical and sexual development in children[J]. Chinese Journal of Contemporary Pediatrics. 2014, 16(5): 555-559 https://doi.org/10.7499/j.issn.1008-8830.2014.05.024

参考文献

[1] Soriano-Guillen L, Corripio R, Labarta JI, et al. Central precocious puberty in children living in Spain: incidence, prevalence, and influence of adoption and immigratio[J]. Clin Endocrinol Metab, 2010, 95(9): 4305-4313.
[2] Massart F, Seppia P, Pardi D, et al, High incidence of central precocious puberty in a bounded geographic area of northwest Tuscany: an estrogen disrupter epidemic? [J]. Gynecol Endocrinol, 2005, 20(2): 92-98.
[3] 林峰, 郑昌华, 李桦, 等. 浙江沿海地区性早熟的调查与研究[J]. 实用儿科临床杂志, 2004, 19(8): 640-642.
[4] 蔡德培. 儿童性早熟的研究进展[J]. 实用儿科临床杂志, 2005, 20(6): 497-499.
[5] 胡华燕, 汪辉龙, 黎娟娟, 等. 九江市城区3~12岁儿童性早熟流行病学调查[J]. 中国儿童保健杂志, 2012, 20(11): 985-987.
[6] 卫海燕, 陈永兴, 李春枝, 等. 郑州地区3~12岁儿童性早熟流行病学调查[J]. 实用儿科临床杂志, 2010, 25(20): 1568-1570.
[7] 张星星, 易著文, 张建江, 等. 性早熟儿童及其父母心理卫生状况初步调查[J]. 中国临床心理学杂志, 2005, 13(5): 348-349.
[8] Franceschi R, Gaudino R, Marcolongo A, et al. Prevalence of polycystic ovary syndrome in young women who had idiopathic central precocious puberty[J]. Fertil Steril, 2010, 93(4): 1185-1191.
[9] 顾再研, 沈永年. 性早熟女童初潮后骨龄、身高增长随访观察[J]. 中国儿童保健杂志, 2004, 12(2): 164-166.
[10] Ko JH, Lee HS, Lim JS, et al. Changes in bone mineral density and bodycomposition in children with central precocious puberty and early puberty before and after one year of treatment with GnRH agonist[J]. Horm Res Paediatr, 2011, 75(3): 174-179.
[11] 汪治华, 闫晓莉, 李小青, 等. 性早熟女童血清IGF-1、瘦素检测及其临床价值探讨[J]. 中国儿童保健杂志, 2011, 19(9): 811-813.
[12] Preamrudee P, Suphasit R, Mahachoklertwattana P. Adult height, body massindex and time of menarche of girls with idiopathic central precocious puberty after gonadotropin-releasing hormone analogue treatment[J]. Gynecol Endocrinol, 2011, 27(8): 524-528.
[13] 朱志颖, 李嫔, 蔡德培. 三种不同类型性早熟女童骨生长及骨代谢变化研究[J]. 临床儿科杂志, 2007, 125(12): 993-995.
[14] Prete G, Couto-Silva AC, Trivin C, et al. Idiopathic central precocious puberty in girls: presentation factors[J]. BMC Pediatrics, 2008, 8(27): 1-8．
[15] Rosenfield RL, Lipton RB, Drum ML. Thelarche, pubarche and menarche attainment in children with normal and elevated body mass index[J]. Pediatrics, 2009, 123(1): 84-88.
[16] Nar A, Demirtas E, Ayhan A, et al. Effects of bilateral ovariectomy and estrogen replacement therapy on serum leptin, sex hormone binding globulinand insulin like growth factor-I levels[J]. Gynecol Endocrinol, 2009, 25(12): 773-778.
[17] 杨雪冰, 李建朝, 张丽娜, 等. 单纯性肥胖男童血清瘦素、性激素水平及其对性发育的影响[J]. 实用儿科临床杂志, 2008, 23(8): 593-594.
[18] Laron Z. Is obesity associated with early sexual maturation? [J]. Pediatrics, 2004, 113(1): 171-172.
[19] Kaplowitz BP. Link between body fat and the timing of puberty[J]. Pediatrics, 2008, 121(3): 208-217.
[20] Su PH, Yang SF, Yu JS, et al. Study of leptin levels and gene polymorphisms in patients with central precocious puberty[J]. Pediatr Res, 2012, 71(4): 361-367.
[21] Donato J Jr, Cravo RM, Frazao R, et al. Leptin's effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons[J]. Clin Invest, 2011, 121(1): 355-368.
[22] Sorensen K, Aksglaede L, Petersen JH, et al. Serum IGF1 and insulin levels in girls with normal and precocious puberty[J]. Eur J Endocrinol, 2012,166(5): 903-910.
[23] 余丽蓉, 杨玉, 吴限, 等. 特发性中枢性性早熟儿童治疗前后胰岛素抵抗相关性研究[J]. 中国妇幼保健杂志, 2013, 28(4): 623-625.
[24] 蔡德培, 时毓民, 陆韺. 女性特发性性早熟下丘脑-垂体-卵巢轴功能及内生殖器官的发育规律[J]. 中华内分泌代谢杂志, 1993, 9(1): 24-26.
[25] Rhie YJ, Lee KH, Eun SH, et al. Serum kisspeptin levels in Korean girls with central precocious puberty[J]. Korean Med Sci, 2011, 26(7): 927-931.
[26] Wolinska-Witort E, Martynska L, Chmielowska M, et al. The evaluation ofestradiol and leptin action on the activity of the somatotropic and gonadotropic axes in peripubertal female rats[J]. Neuro Endocrinol Lett, 2012, 33(2): 138-148.
[27] Hsieh CC, Trichopoulos D, Katsouyanni K, et al. Age at menarche, age atmenopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case-control study[J]. Int J Cancer 1990, 46(15): 796-800.
[28] 梁雁, 应艳琴, 罗小平. 儿童性早熟诊断和治疗中应该重视的问题[J]. 中华儿科杂志, 2011, 49(6): 401-404.
[29] Lewis KA, Eugster EA. Random luteinizing hormone often remains pubertal in children treated with the histrelin Implant for central precocious puberty[J]. J Pediatr, 2013, 162(3): 562-565.
[30] Fuld K, Chi C, Neely EK. A randomized trial of 1- and 3-month depot leuprolide doses in the treatment of central precocious puberty[J]. J Pediatr, 2011, 159(6): 982-987.
[31] Allali S, Lemaire P, Couto-Silva AC, et al. Predicting the adult height of girls with central precocious puberty[J]. Med Sci Moni, 2011, 17(6): 41-48.
[32] Lee PA, Neely EK, Fuqu J, et al. Efficacy of leuprolide acetate 1-month depot central precocious puberty (CPP): growth outcomes during a prospective, longitudinal study[J]. Int J Pediatric Endocrinol, 2011, 2011(1): 1-7.
[33] Massart F, Federico G, Harrel JC, et al. Growth outcome during GnRH agonist treatments for slowly progressive central precocious puberty[J]. Neuroendocrinology, 2009, 90(3): 307-314.
[34] 马华梅, 杜敏联, 李燕虹, 等. GnRHa治疗真性性早熟过程中生长速度的相关因素分析[J]. 中华内分泌代谢杂志, 2007, 23(5): 388-391.
[35] 朱顺叶, 陈红珊, 马华梅, 等. 蛋白同化类固醇激素对GnRHa治疗后中枢性性早熟患儿生长的影响[J]. 中国儿童保健杂志, 2009, 17(1): 51-53.
[36] Brito VN, Latronico AC, Cukier P, et al. Factors determining normal adultheight in girls with gonadotropin-dependent precocious puberty treated withdepot gonadotropin releasing hormone analogs[J]. Clin Endocrinol Metab, 2008, 93(7): 2662-2669.
[37] Carel JC. Management of short stature with GnRH agonist and co-treatment with growth hormone：a controversial issue[J]. Mol Cell Endocrinol, 2006, 25(254-255): 226-233.
[38] 郑丕媚, 苏酤, 马华梅, 等. 生长激素对于GnRHa治疗中生长过度减速的特发性中枢性性早熟女孩的远期疗效观察[J]. 中华内分泌代谢杂志, 2011, 27 (4): 287-291.
[39] 王春林, 梁黎, 留佩宁, 等. 促性腺激素释放激素类似物联合重组人生长激素对中枢性性早熟女童身高的影响[J]. 中国当代儿科杂志, 2012, 16(1): 25-30.
[40] Taccilar ME, Bilir P, Akinci A, et al. The effect of gonadotropin-releasing hormone analog treatment (leuprolide) on body fat distribution in idiopathic central precocious puberty[J]. Tur J Pediatric, 2011, 53(1): 27-33.
[41] Chiocca E, Dati E, Baroncelli GI, et al. Body mass index and body composition in adolescents treated with gonadotropin releasin hormone analogue triptorelin depot for central precocious puberty: data at near final height[J]. Neuroendocrinology, 2009, 89(4): 441-447.
[42] Karamizadeh Z, Tabebordbar M, Saki F, et al. The side effects of gonadotropin-releasing hormone analog (diphereline) in treatment of idiopathic central precocious puberty[J]. Acta Medica Iranica, 2013, 51(1): 41-46.
[43] Lee HS, Park HK, Ko JH, et al. Impact of body mass index on luteinizing hormone secretion in gonadotropin releasing hormone stimulation tests ofboys experiencing precocious puberty[J]. Neuroendocrinology, 2013, 97(3): 225-231.
[44] Glab E, Barg E, Wikiera B, et al. Influence of GnRH analog therapy on body mass in central precocious puberty[J]. Pediatr Endocrinol Diabetes Metab, 2009, 15(1): 7-11.
[45] Park HK, Lee HS, Ko JH, et al. The effect of gonadotrophin-releasing hormone agonist treatment over 3 years on bone mineral density and body composition in girls with central precocious puberty[J]. Clin Endocrinol, 2012, 77(5): 743-748.
[46] Inman M, Hursh BE, Mokashi A, et al. Occurrence of slipped capital femoral epiphysis in children undergoing gonadotropin releasing hormone agonist therapy for the treatment of central precocious puberty[J]. Horm Res Paediatr, 2013, 80(1): 64-68.
[47] Seminara S, Nanni L, Generoso M, et al. Effect of treatment with cyproterone acetate on uterine bleeding at the beginning of GnRH analogue therapy in girls with idiopathic central precocious puberty[J]. Horm Res Paediatr, 2010, 73(5): 386-388.
[48] Seminara S, Nanni L, Generoso M, et al. Effect of treatment with cyproterone acetate on uterine bleeding at the beginning of GnRH analogue therapy in girls with idiopathic central precocious puberty[J]. Horm Res Paediatr, 2010, 73(5): 386-389.
[49] Naor Z, Jabbour HN, Naidich M, et al. Reciprocal cross talk between gonadotropin-releasing hormone（GnRH）and prostaglandin receptors regulates GnRH receptor expression and differential gonadotropin secretion[J]. Mol Endocrinol, 2007, 21(2): 524-537.
[50] Kauschansky A, Orvieto R, Yeshaya A, et al. Insight: prolonged vaginal bleeding during central precocious puberty therapy with a long-acting gonadotropin-releasing hormone agonist: a proposed mechanism and management plan[J]. J Pediatr Adolesc Gynecol, 2011, 24(6): 365-367.
[51] Heger S, Muller M, Ranke M, et al. Long-term GnRH agonist treatment for female central precocious puberty does not impair reproductive function[J]. Mol Cell Endocrinol, 2006, 25(254-255): 217-220.
[52] Chiavaroli V, Liberati MD, Antonio F, et al. GnRH analog therapy in girlswith early puberty is associated with the achievement of predicted final height but also with increased risk of polycystic ovary syndrome[J]. Eur J Endocrinol, 2010, 163(1): 55-62.