Introduction Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing. Methods Embase, Medline, and Cochrane library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children. Results Twenty-five articles (n=1,438 children) were identified describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n=6 studies), chronic renal failure (n=3), Noonan syndrome (n=1), and growth hormone deficiency (n=1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference=-0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total=402) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total=284). Conclusions Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.


中文翻译：

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生长激素治疗对青春期时间的影响：系统评价和荟萃分析

简介 重组人生长激素 (rhGH) 疗法可有效增加各种儿童生长障碍患者的身高。然而，rhGH 是否影响青春期时间尚不清楚。我们旨在系统地回顾已发表的关于 rhGH 对青春期时间影响的证据。方法 在 Embase、Medline 和 Cochrane 图书馆数据库中搜索了截至 2021 年 12 月的关于儿童 rhGH 的随机和非随机对照研究。结果 确定了 25 篇文章（n=1,438 名儿童），描述了 12 项随机和 13 项非随机对照研究，这些研究针对特发性矮小（ISS；15 项研究）、小于胎龄儿（n=6 项研究）、慢性肾功能衰竭(n=3)、Noonan 综合征 (n=1) 和生长激素缺乏症 (n=1)。临床适应症发现 rhGH 对青春期时间的影响存在显着差异。仅在患有 ISS 的儿童中，rhGH 促进了青春期时间的提早（平均差异=-0.46 岁；95% CI，-0.90 至-0.03；9 项研究；n 总数=402）或研究随访期间青春期开始的相对风险更高-上升（1.26；95% CI，1.03 至 1.54；6 项研究；n 总数 = 284）。结论 rhGH 治疗似乎可以促进 ISS 儿童青春期提前。由于缺乏未经治疗的对照研究，缺乏生长激素缺乏症儿童的证据。6项研究；n 总数 = 284)。结论 rhGH 治疗似乎可以促进 ISS 儿童青春期提前。由于缺乏未经治疗的对照研究，缺乏生长激素缺乏症儿童的证据。6项研究；n 总数 = 284)。结论 rhGH 治疗似乎可以促进 ISS 儿童青春期提前。由于缺乏未经治疗的对照研究，缺乏生长激素缺乏症儿童的证据。