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J Zhejiang Univ (Med Sci)
    
Aromatase inhibitors combined with growth hormone in treatment of adolescent boys with short stature
KONG Yuanmei, CHEN Hong, LIANG Li, ZHENG Maoni, FANG Yanlan, WANG Chunlin
Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
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Abstract  Objective: To assess the efficacy and safety of aromatase inhibitors(AIs) combined growth hormone in treatment of adolescent boys with short stature. Methods: One hundred and fifty-one short stature pubertal boys with age of 10-14 year and bone age of 13-15 years, who were admitted to the Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, were included in this trial. According to their own or parents' intention patients were divided into AIs+rhGH group (n=108) and rhGH group (n=43). All patients were injected subcutaneously with recombinant human growth hormone (rhGH) 0.15~0.2 IU/kg·d, those in AIs +rhGH group were additionally given 1 mg anastrozole or 2.5 mg letrozole q.d. orally for 12 months or longer. Patients were followed-up every 3 months. During the follow-up visit, the predicted adult height (PAH), sex hormone level, glucose and lipid metabolism and other indicators were measured, and adverse reactions were monitored. Results: After intervention, there were significant differences in △BA(bone age)/△CA(chronological age), △HtSDS-BA(height standard deviation-based on bone age)and △PAH between AIs+ rhGH group and the rhGH group(P=0.003, 0.024 and 0.015, respectively). During follow-up, 63.89% of the boys in the AIs+ rhGH group had elevated uric acid and 51.85% had decreased high-density lipoprotein (HDL); 25.93% showed severe acne, excitement, hyperactivity and irritability, 11.11% had knee pain, 4.63% had fracture, 2.78% had mild renal dysfunction, 1.85% had inactivity, drowsiness, memory loss and performance decline. In addition, 1.85% of the boys showed mild abnormal liver function, 0.93% showed impaired fasting glucose, and 0.93% showed granulocytopenia. In the rhGH group, 11.63% of patients presented with knee pain and 2.33% with impaired fasting glucose. Conclusion: AIs combined with rhGH can delay the growth of BA and effectively improve the PAH of adolescent boys with larger bone age. However, the occurrence of adverse reactions of AIs should be closely monitored during treatment. The effects of letrozole and anastrozole on adolescent boys with larger bone age and short stature need to be further studied.

Key wordsShort stature      Aromatase inhibitors      Recombinant human growth hormone      Puberty      Boys     
Received: 09 January 2020      Published: 29 May 2020
CLC:  R588  
  R725.8  
Cite this article:

KONG Yuanmei, CHEN Hong, LIANG Li, ZHENG Maoni, FANG Yanlan, WANG Chunlin. Aromatase inhibitors combined with growth hormone in treatment of adolescent boys with short stature. J Zhejiang Univ (Med Sci), 0, 0(0): 6-0.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2020.04.06     OR     http://www.zjujournals.com/med/Y0/V0/I0/6


芳香化酶抑制剂联合生长激素治疗青春期矮身材男童的临床研究

目的:研究第三代非甾体类芳香化酶抑制剂(AI)改善大骨龄(≥ 13岁)男性矮身材青少年的成年身高的有效性,同时监测药物的安全性。方法:2015年12月-2018年11月在浙江大学医学院附属第一医院就诊的预测成年身高受损的13岁≤骨龄≤ 15岁的青春期男孩151例,经充分告知AI的药物潜在风险后,由患儿及其家长选择入组:AIs+重组人生长激素(rhGH)联用组108例,单用rhGH组43例。治疗时间12月以上,每3个月复查一次,监测不良反应。结果:与rhGH单用组比较,AI+rhGH联用组骨龄差值/生理年龄差值(△BA/△CA)、按骨龄的身高标准差分值的差值(△HtSDS-BA)以及预测成年身高的差值(△PAH)改善更加明显(P<0.05或P<0.01)。随访期间,AI+rhGH联用组尿酸升高69例(63.89%),高密度脂蛋白(HDL)降低56例(51.85%),出现严重痤疮、兴奋多动、性格暴躁28例(25.93%),出现膝关节疼痛12例(11.11%),发生骨折5例(4.63%),出现轻度肾功能异常3例(2.78%),出现精神不振、嗜睡、记忆力减退和成绩下降2例(1.85%),出现轻度肝功能异常2例(1.85%),空腹血糖受损1例(0.93%),粒细胞减少1例(0.93%),停药后监测指标逐渐正常。rhGH单用组出现膝关节疼痛5例(11.63%),空腹血糖受损1例(2.33%)。结论:长疗程的AI联合rhGH治疗可以延缓骨龄增长,有效改善青春期大骨龄矮小男孩的成年终身高,但治疗期间需要密切监测AI的不良反应;来曲唑与阿那曲唑在改善大骨龄矮身材男孩治疗上的差异有待进一步研究。

关键词: 身材矮小症,  芳香化酶抑制剂,  重组人生长激素,  青春期,  男童 
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