ObjectiveTo evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). MethodSeventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. ResultsHV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group ( P < 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) ( t=2.78 and 2.20, all P < 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups ( P>0.05), and both were higher than that in no intervention group (162±4 cm, P < 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. ConclusionsLong term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.
目的: 观察和评估芳香化酶抑制剂来曲唑治疗已进入青春期的特发性身材矮小症（ISS）男性患儿的疗效和安全性。
方法: 收集2004—2017年在中山大学附属第一医院儿科内分泌专科门诊就诊，身高低于同年龄、同性别平均水平2个标准差以下并已经进入青春期的ISS男性患儿75例，按所选择的治疗方案分为来曲唑组、促性腺激素释放激素类似物（GnRHa）组和无干预组。其中，来曲唑组28例，应用来曲唑治疗，剂量为1.5~2.0 mg·m -2·d -1（最大剂量不超过2.5 mg/d），1次/d顿服，同时给予螺内酯1~2 mg·kg -1·d -1，分次口服；GnRHa组30例，采用GnRHa治疗，首剂3.75 mg，以后按60~100 μg/kg每28 d注射1次；无干预组17例，无任何干预措施。比较各组身高增长速度（HV）、骨龄差值/时序年龄差值比值（ΔBA/ΔCA）及成年身高，同时观察来曲唑治疗的不良反应。
结果: 来曲唑组在治疗过程中HV维持在相对较高水平，而GnRHa组治疗的前半年HV稍低于来曲唑组，半年后HV回落明显，显著低于来曲唑组（ P < 0.05）。在骨龄控制方面，来曲唑组第一年和次年的ΔBA/ΔCA逐渐下降，分别为0.67±0.09和0.50±0.15；而GnRHa组则分别为0.59±0.16和0.44±0.13，均低于来曲唑组且差异有统计学意义（ t=2.78和2.20，均 P < 0.05）。来曲唑及GnRHa治疗后患儿成年身高分别为（170±4）cm和（170±6）cm，差异无统计学意义（ P>0.05），均高于无干预组患儿成年身高（162±4）cm（均 P < 0.01）。来曲唑治疗6个月后，患儿睾丸容积及血睾酮增加。39.2%（11/28）的患儿出现高雄激素临床表现，82.1%（23/28）的患儿治疗过程中出现血高密度脂蛋白（HDL）降低，终止治疗后高雄激素表现消失，血睾酮及血HDL恢复正常。血三酰甘油、血低密度脂蛋白（LDL）、空腹胰岛素、血糖及胰岛素抵抗指数在治疗过程中无显著变化（均 P>0.05），未见肝功能异常、关节或肌肉疼痛、脊柱侧弯发生或加重者。
结论: 对于青春期ISS男性患儿，长疗程来曲唑可有效延缓骨龄增长，同时不会使HV减速，从而达到有效改善成年身高的远期效果，且未见明显不良反应。