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.

中文翻译：

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青春期生长障碍的管理：GH、GnRHa 和芳香化酶抑制剂：临床回顾。

具有显着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) 缺乏症和那些没有可识别病症（特发性身材矮小）的患者中，使用 GH 的影响受到性类固醇引起的骨龄加速无休止节奏的显着阻碍，限制了可用于生长的时间。雌激素主要调节女性和男性的骨骺融合。GH 的产生率和生长速度在青春期增加一倍以上，高剂量 GH 的使用显示线性生长呈剂量依赖性增加，但也会超生理地提高胰岛素样生长因子 I 的浓度，并增加治疗成本。促性腺激素释放激素类似物 (GnRHas) 抑制生理性青春期，当与 GH 结合使用时，可以显着提高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性腺功能减退。芳香化酶抑制剂 (AI) 阻断雄激素向雌激素的转化，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生长。在这里，我们回顾了青春期生长的生理学、雌激素和雄激素对骨骺的作用，以及单独使用 GH 以及与 GnRHa 和 AI 联合使用时的治疗效果。还回顾了强效口服 AI 的药理学及其在儿童中的有效性和安全性的关键工作。限时使用 AI 是促进青春期男性生长的可行替代方案，尤其是与 GH 结合使用时。