Weise Martina, Flor Armando, Barnes Kevin M, Cutler Gordon B, Baron Jeffrey
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, USA.
J Clin Endocrinol Metab. 2004 Jan;89(1):103-7. doi: 10.1210/jc.2002-021999.
In children with precocious puberty (PP), treatment with GnRH analogs (GnRHa) often decreases height velocity below normal. Based on previous animal studies, we hypothesized that this impaired growth is due to excessive advancement in growth plate senescence induced by the prior estrogen exposure. This hypothesis predicts that the height velocity during treatment will be inversely related to the severity of prior estrogen exposure. We analyzed data from 100 girls (age, 5.8 +/- 2.1 yr; mean +/- SD) with central PP who were treated with GnRHa. During GnRHa therapy, height velocity was low for age (-1.6 +/- 1.7 SD score; mean +/- SD). The absolute height velocity correlated most strongly with the bone age (BA), which we used as a surrogate marker for growth plate senescence (r = -0.727, P < 0.001). The severity of the growth abnormality (height velocity SD score for age) correlated inversely with markers of the severity of prior estrogen exposure, including duration of PP (r = -0.375, P < 0.001), Tanner breast stage (r = -0.220, P < 0.05), and BA advancement (r = -0.283, P < 0.01). Stepwise regression confirmed that BA was the best independent predictor of growth during GnRHa therapy. The findings are consistent with our hypothesis that impaired growth during GnRHa therapy is due, at least in part, to premature growth plate senescence induced by the prior estrogen exposure.
在性早熟（PP）儿童中，使用促性腺激素释放激素类似物（GnRHa）治疗常常会使身高增长速度降至正常水平以下。基于先前的动物研究，我们推测这种生长受损是由于先前雌激素暴露诱导生长板衰老过度进展所致。该假说预测治疗期间的身高增长速度将与先前雌激素暴露的严重程度呈负相关。我们分析了100名接受GnRHa治疗的中枢性性早熟女孩（年龄5.8±2.1岁；均值±标准差）的数据。在GnRHa治疗期间，身高增长速度低于同龄人水平（标准差评分为-1.6±1.7；均值±标准差）。绝对身高增长速度与骨龄（BA）的相关性最强，我们将骨龄用作生长板衰老的替代标志物（r = -0.727，P < 0.001）。生长异常的严重程度（年龄别身高增长速度标准差评分）与先前雌激素暴露严重程度的标志物呈负相关，这些标志物包括性早熟持续时间（r = -0.375，P < 0.001）、坦纳乳房分期（r = -0.220，P < 0.05）和骨龄进展（r = -0.283，P < 0.01）。逐步回归分析证实骨龄是GnRHa治疗期间生长的最佳独立预测指标。这些发现与我们的假说一致，即GnRHa治疗期间生长受损至少部分是由于先前雌激素暴露诱导的生长板过早衰老所致。
