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J Zhejiang Univ (Med Sci)  2020, Vol. 49 Issue (3): 275-282    DOI: 10.3785/j.issn.1008-9292.2020.04.01
    
Reconsideration of the third-generation non-steroidal aromatase inhibitors in pediatrics
WANG Chunlin(),LIANG Li*()
Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
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Abstract  

Aromatase is the rate-limiting enzyme in estrogen biosynthesis. The third generation aromatase inhibitors (AIs), represented by letrozoleand and anastrozole, can combine with aromatase, effectively reducing the estrogen level in the body. Because of its high efficiency, selectivity and reversibility, it has been used in the treatment of McCune-Albright syndrome, familial male-limited precocious puberty, gynecomastia, and adolescent boy with short stature. The good efficacy and safety of AIs have been observed. However, so far the drug instructions of AIs usually do not show indications for children; there are risks of adverse reactions involving liver and kidney function, lipid metabolism, hyperandrogenemia and bone metabolism; especially the long-term effects on reproductive system and bone metabolism are still not clear. Therefore, it is necessary to prescribe it carefully and follow up closely. It was not recommended that AIs be routinely used to improve adult height of adolescent boy with short stature. And more clinical evidences are needed for the safety and effectiveness of AIs prescribed in pediatrics.



Key wordsAromatase inhibitors/therapeutic use      Child      Treatment outcome      Safety     
Received: 29 November 2019      Published: 29 May 2020
CLC:  R588  
  R725.8  
Corresponding Authors: LIANG Li     E-mail: hzwangcl@zju.edu.cn;zdliangli@zju.edu.cn
Cite this article:

WANG Chunlin,LIANG Li. Reconsideration of the third-generation non-steroidal aromatase inhibitors in pediatrics. J Zhejiang Univ (Med Sci), 2020, 49(3): 275-282.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2020.04.01     OR     http://www.zjujournals.com/med/Y2020/V49/I3/275


第三代非甾体类芳香化酶抑制剂在儿科内分泌临床应用的再认识

芳香化酶是雌激素生物合成的限速酶,以来曲唑和阿那曲唑为代表的第三代非甾体类芳香化酶抑制剂(AI)与芳香化酶结合,可有效降低雌激素水平,因其具有高效性、选择性及可逆性结合等特点,近20年来在国内外被应用于儿童内分泌疾病如纤维性骨营养不良综合征、家族性男性限制性性早熟、青春期男性乳房发育治疗和改善青春期矮小男童成年终身高等,观察到较好的疗效和安全性。然而,AI药品说明书并无儿童用药适应证,较大样本量的临床研究发现AI存在肝肾功能损害、脂代谢紊乱、高雄激素血症及骨代谢紊乱等药物不良反应的风险,尤其是对男性生殖系统损害和骨代谢的远期影响尚不清楚。因此,儿童使用AI时须权衡利弊、谨慎使用,通过收集AI安全性和有效性的临床证据积累经验,为规范AI在儿科的临床应用奠定基础。


关键词: 芳香酶抑制剂/治疗应用,  儿童,  治疗结果,  安全性 
种类 第一代 第二代 第三代
药物名称 适应证 药物名称 适应证 药物名称 适应证
甾体类 睾内酯 乳腺癌姑息性治疗 福美司坦 用于自然或人工绝经的乳腺癌患者 依西美坦 适用于以他莫昔芬治疗后病情进展的绝经后晚期乳腺癌患者
非甾体类 氨鲁米特 主要适用于绝经后晚期乳腺癌、乳腺癌骨转移、皮质醇增多症的治疗 法曲唑 绝经期后乳腺癌 来曲唑 用于治疗抗雌激素治疗无效的晚期乳腺癌绝经后患者
阿那曲唑 用于绝经后妇女的晚期乳腺癌的治疗
Tab 1 Classification and indications of aromatase inhibitors
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