Please wait a minute...
J Zhejiang Univ (Med Sci)
    
Efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development
YU Bingqing, NIE Min, WU Xueyan, MAO Jiangfeng, WANG Xi, MA Wanlu, JI Wen, HUANG Qibin, ZHANG Rui
Department of Endocrinology, National Health Commission Key laboratory of Endocrinology, Peking Union Medical College Hospital, PekingUnion Medical College, Chinese Academy ofMedical Sciences, Beijing, China
Download: HTML (   PDF(404KB)
Export: BibTeX | EndNote (RIS)      

Abstract  Objective: To investigate the efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development (DSD). Methods: Clinical data of 12 male DSD children with a mean age of 14.6 ±2.5 years admitted to Peking Union Medical College Hospital from January 2014 to January 2016 were retrospectively analyzed. The patients treated with treated with letrozole (1.25~2.5mg, q.d) for 3 months or longer, and followed up for 0.5~2.5 years. Clinical manifestation and laboratory test finding were documented and the efficacy and safety were evaluated. Results: The baseline luteinizing hormone (LH) level before treatment was 5.2 (3.7, 16.5) IU/L, follicle-stimulating hormone(FSH) level was 14.1 (5.3, 24.7) IU/L, testosterone level was 5.2 (3.8, 10.0) nmol/L, and E2 level was (120.7±51.0)pmol/L. After half a year of treatment, the blood LH, FSH and testosterone levels of patients increased (all P<0.05), and estrogen levels decreased from baseline (P<0.05). After 1 year of treatment, the blood testosterone level was significantly higher than that before treatment (P<0.05); the LH and FSH levels tended to increase and the estrogen level tended to decrease than the baseline, but there was no significant statistical difference (P>0.05). Semen was routinely detected in 8 patients, and sperms were detected in semen of 3 patients with hypospadias. There were no significant adverse events in all patients during the treatment, and no significant changes in biochemical results after treatment. Conclusion: Aromatase inhibitor letrozole can effectively increase testosterone levels in patients with disorders of sex development and promote spermatogenesis, it has no significant adverse effects in short-term administration.

Key wordsDisorders of sex development/drug therapy      Aromatase inhibitors/therapeutic use      Testosterone      Estrogens      Child     
Received: 15 December 2019      Published: 29 May 2020
CLC:  R588  
  R725.8  
Cite this article:

YU Bingqing, NIE Min, WU Xueyan, MAO Jiangfeng, WANG Xi, MA Wanlu, JI Wen, HUANG Qibin, ZHANG Rui. Efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development. J Zhejiang Univ (Med Sci), 0, 0(0): 2-0.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2020.04.02     OR     http://www.zjujournals.com/med/Y0/V0/I0/2


芳香化酶抑制剂有效提高性发育异常儿童的睾酮水平

目的:评价芳香化酶抑制剂来曲唑治疗男性性发育异常(DSD)患儿的疗效和安全性。方法:收集2014年1月至2016年1月就诊于北京协和医院内分泌科门诊的男性DSD患儿12例,其中来曲唑治疗≥ 3个月的患者采集其临床资料及实验室检查结果,比较治疗前后激素水平及生化指标的差异,并观察治疗中的不良反应。结果:本组患儿来曲唑治疗的平均年龄为(14.6±2.5)岁。来曲唑治疗半年后患者血促性腺激素黄体生成素(LH)、卵泡刺激素(FSH)及睾酮水平较基线升高(均P<0.05),雌二醇水平较基线下降(P<0.05);治疗1年后患者睾酮水平较基线高(P<0.05),LH及FSH水平较基线高,雌二醇水平较基线下降,但差异无统计学意义(均P>0.05)。8例患者进行精液常规检测,其中3例尿道下裂患者精液中可检测到精子。所有患者用药后无明显不良反应,监测治疗前后生化检查无明显变化。结论:来曲唑可有效升高性发育异常患者的睾酮水平,促进精子生成,且短期应用未见明显不良反应。

关键词: 性发育障碍/药物疗法,  芳香酶抑制剂/治疗应用,  睾酮,  雌激素类,  儿童 
[1] RAMAN J D, SCHLEGEL P N. Aromatase inhibitors for male infertility[J]. J Urol, 2002,167(2 Pt 1):624-629. DOI:10.1097/00005392-200202000-00038.
[2] DEL GIUDICE F, BUSETTO G M, DE BERARDINIS E, et al. A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility[J]. Asian J Androl, 2019. DOI:10.4103/aja.aja_101_19.
[3] TAN R B, GUAY A T, HELLSTROM W J. Clinical use of aromatase inhibitors in adult males[J]. Sex Med Rev, 2014,2(2):79-90. DOI:10.1002/smrj.23.
[4] 刘兆祥, 茅江峰, 伍学焱, 等. 芳香化酶抑制剂(来曲唑)可有效治疗男性部分性特发性低促性腺激素性性腺功能减退症[J]. 中华内分泌代谢杂志, 2016, 32(2):125-127. DOI:10.3760/cma.j.issn.1000-6699.2016.02.009. LIU Zhaoxiang, MAO Jiangfeng, WU Xueyan, et al. Aromatase inhibitor (letrozole) in effective in activating the function of hypothalamus-pituitary-gonad axis in male patients with partial idiopathic hypogonadotropic hypogonadism[J]. Chinese Journal of Endocrinology and Metabolism, 2016, 32(2):125-127. DOI:10.3760/cma.j.issn.1000-6699.2016.02.009. (in Chinese)
[5] LOVES S, DE JONG J, VAN SORGE A, et al. Somatic and psychological effects of low-dose aromatase inhibition in men with obesity-related hypogonadotropic hypotestosteronemia[J]. Eur J Endocrinol, 2013,169(5):705-714. DOI:10.1530/EJE-13-0190.
[6] MITWALLY M F, CASPER R F. Aromatase inhibitors for the treatment of infertility[J]. Expert Opin Investig Drugs, 2003,12(3):353-371. DOI:10.1517/13543784.12.3.353.
[7] WISNIEWSKI A B, BATISTA R L, COSTA E, et al. Management of 46,xy differences/disorders of sex development (dsd) throughout life[J]. Endocr Rev, 2019,40(6):1547-1572. DOI:10.1210/er.2019-00049.
[8] MEHTA A, CLEARMAN T, PADUCH D A. Safety and efficacy of testosterone replacement therapy in adolescents with Klinefelter syndrome[J]. J Urol, 2014,191(5 Suppl):1527-1531. DOI:10.1016/j.juro.2013.09.015.
[9] MEHTA A, BOLYAKOV A, ROOSMA J, et al. Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor[J]. Fertil Steril, 2013,100(4):970-974. DOI:10.1016/j.fertnstert.2013.06.010.
[10] SCHIFF J D, PALERMO G D, VEECK L L, et al. Success of testicular sperm extraction[corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome[J]. J Clin Endocrinol Metab, 2005,90(11):6263-6267. DOI:10.1210/jc.2004-2322.
[11] MOON J E, KO C W, YANG J D, et al. Combined surgical and medical treatment in an adolescent with severe gynecomastia due to excessive estradiol secretion:a case report[J]. BMC Pediatr, 2019,19(1):515. DOI:10.1186/s12887-019-1887-7.
[12] MA N S, GEFFNER M E. Gynecomastia in prepubertal and pubertal men[J]. Curr Opin Pediatr, 2008,20(4):465-470. DOI:10.1097/MOP.0b013e328305e415.
[13] SALTZSTEIN D, SIEBER P, MORRIS T, et al. Prevention and management of bicalutamide-induced gynecomastia and breast pain:randomized endocrinologic and clinical studies with tamoxifen and anastrozole[J]. Prostate Cancer Prostatic Dis, 2005,8(1):75-83. DOI:10.1038/sj.pcan.4500782.
[14] PARADA-BUSTAMANTE A, RÍOS R, EBENSPERGER M, et al. 46,XX/SRY-negative true hermaphrodite[J]. Fertil Steril, 2010,94(6):2330.e13-6. DOI:10.1016/j.fertnstert.2010.03.066.
[15] WIT J M, HERO M, NUNEZ S B. Aromatase inhibitors in pediatrics[J]. Nat Rev Endocrinol, 2011,8(3):135-147. DOI:10.1038/nrendo.2011.161.
[1] CHEN Zhimin,FU Junfen,SHU Qiang,WANG Wei,CHEN Yinghu,HUA Chunzhen,LI Fubang,LIN Ru,TANG Lanfang,WANG Tianlin,WANG Yingshuo,XU Weize,YANG Zihao,YE Sheng,YUAN Tianming,ZHANG Chenmei,ZHANG Yuanyuan. Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 139-146.
[2] LIN Jing,CHEN Zhimin. Research progress on early identification of severe adenovirus pneumonia in children[J]. J Zhejiang Univ (Med Sci), 2019, 48(5): 567-572.
[3] NIU Yubai,ZHANG Lingyan,HAO Zesheng,JI Yuzhu. Relationship between temperament, parenting style and resilience of children aged 3-5 years[J]. J Zhejiang Univ (Med Sci), 2019, 48(1): 75-82.
[4] HE Jiayi,ZHANG Xinmei. Research progress on oxidative stress in pathogenesis of endometriosis[J]. J Zhejiang Univ (Med Sci), 2018, 47(4): 419-425.
[5] XU Weize,YE Jingjing,LI Jianhua,ZHANG Zewei,YU Jiangen,SHI Zhuo,YU Jin,SHU Qiang. Efficacy of percutaneous atrial septal defect closure guided by transesophageal echocardiography in children[J]. J Zhejiang Univ (Med Sci), 2018, 47(3): 244-249.
[6] SONG Chunze,JIANG Guoping,YE Jingjing,HE Jin,YU Jin. Echocardiography in diagnosis of pediatric pulmonary artery sling[J]. J Zhejiang Univ (Med Sci), 2018, 47(3): 250-254.
[7] HUANG Ting,ZHANG Xiaole,LIANG Liang,TAN Zheng,GAO Yue,LI Jianhua,SHU Qiang. Endoscopic lobectomy for 47 children with pulmonary sequestration[J]. J Zhejiang Univ (Med Sci), 2018, 47(3): 272-277.
[8] PENG Dandan,ZHOU Xudong. Parents' antibiotic use for children in Ningbo: knowledge, behaviors and influencing factors[J]. J Zhejiang Univ (Med Sci), 2018, 47(2): 156-162.
[9] ZHENG Qi,LU Meiping. Focus on pediatric rheumatic and immune diseases[J]. J Zhejiang Univ (Med Sci), 2018, 47(2): 213-217.
[10] WANG Liya, QIAN Yeqing, JIN Fan. Research progress on the safety of offsprings conceived by assisted reproductive technology[J]. J Zhejiang Univ (Med Sci), 2017, 46(3): 279-284.
[11] CHEN Yonghua,LIANG Li,FANG Yanlan,WANG Chunlin,LI Linfa,JIANG Tian'an. Iodine 131 joint radio frequency ablation treatment for child with hyperthyroidism goiter: one case report[J]. J Zhejiang Univ (Med Sci), 2017, 46(1): 89-91.
[12] CHEN Xiaohong, XU Yiping, LU Meiping. Clinical characteristics and etiology of children with hypereosinophilia[J]. J Zhejiang Univ (Med Sci), 2016, 45(3): 292-296.
[13] LIN Kai-qing, ZHU Li-bo, ZHANG Xin-mei, LIN Jun. Role of mast cells in estrogen-mediated experimental endometriosis in rats[J]. J Zhejiang Univ (Med Sci), 2015, 44(3): 269-277.
[14] CHEN Lianhui,LIANG Li,FU Junfen,ZHU Weifen,WANG Chunlin,HUANG Ke,FANG Yan. Comparison of clinical application of two definitions of metabolic syndrome in children and adolescents[J]. J Zhejiang Univ (Med Sci), 2013, 42(4): 375-.
[15] LIN Hu,FU Junfen,CHEN Xuefeng,HUANG Ke,WU Wei,LIANG Li. Early identification of impaired renal function in obese children with non-alcoholic fatty liver disease[J]. J Zhejiang Univ (Med Sci), 2013, 42(4): 381-.