Abstract：
Pubertal children with significant growth retardation represent a considerable therapeutic challenge. In growth hormone (GH) deficiency, and in those without identifiable pathologies (idiopathic short stature), the impact of using GH is significantly hindered by the relentless tempo of bone age acceleration caused by sex steroids, limiting time available for growth. Estrogen principally modulates epiphyseal fusion in females and males. GH production rates and growth velocity more than double during puberty, and high-dose GH use has shown dose-dependent increases in linear growth, but also can raise insulin-like growth factor I concentrations supraphysiologically, and increase treatment costs. Gonadotropin-releasing hormone analogs (GnRHas) suppress physiologic puberty, and when used in combination with GH can meaningfully increase height potential in males and females while rendering adolescents temporarily hypogonadal at a critical time in development. Aromatase inhibitors (AIs) block androgen to estrogen conversion, slowing down growth plate fusion, while allowing normal virilization in males and stimulating longitudinal bone growth via androgen receptor effects on the growth plate. Here, we review the physiology of pubertal growth, estrogen and androgen action on the epiphyses, and the therapeutic impact of GH, alone and in combination with GnRHa and with AIs. The pharmacology of potent oral AIs, and pivotal work on their efficacy and safety in children is also reviewed. Time-limited use of AIs is a viable alternative to promote growth in pubertal males, particularly combined with GH. Use of targeted growth-promoting therapies in adolescence must consider the impact of sex steroids on growth plate fusion, and treatment should be individualized.
摘要：
患有严重生长迟缓的青春期儿童代表了相当大的治疗挑战。在生长激素（GH）缺乏，在那些没有可识别的病理(特发性身材矮小)的人中，使用GH的影响受到由性类固醇引起的骨龄加速的无情节奏的显著阻碍，限制可用于增长的时间。雌激素主要调节女性和男性的骨phy融合。在青春期，GH的生产率和生长速度增加了一倍以上，高剂量GH的使用显示线性增长的剂量依赖性增加，而且可以提高胰岛素样生长因子I的超生理浓度，增加治疗费用。促性腺激素释放激素类似物（GnRHas）抑制生理青春期，当与GH结合使用时，可以有意义地增加男性和女性的身高潜力，同时使青少年在发育的关键时刻暂时性腺功能低下。芳香化酶抑制剂（AIs）阻断雄激素向雌激素转化，减缓生长板融合，同时允许男性正常男性化，并通过雄激素受体对生长板的作用刺激纵向骨骼生长。这里,我们回顾了青春期生长的生理学，雌激素和雄激素对骨的影响，以及GH的治疗效果，单独使用，并与GnRHa和AI结合使用。强效口服AIs的药理学，并对其在儿童中的疗效和安全性的关键工作进行了审查。限时使用AI是促进青春期男性生长的可行替代方法，特别是结合GH。在青春期使用有针对性的促生长疗法必须考虑性类固醇对生长板融合的影响，治疗应该是个性化的。
