Kunz Gregory J, Sherman Tami Irwin, Klein Karen Oerter
Division of Pediatric Endocrinology, University of California, San Diego, CA, USA.
J Pediatr Endocrinol Metab. 2007 Nov;20(11):1189-98. doi: 10.1515/jpem.2007.20.11.1189.
Girls with central precocious puberty (CPP) are treated with gonadotropin releasing hormone (GnRH) analogues to suppress puberty. Gonadotropin levels are used to monitor treatment, since estradiol is difficult to measure at low levels. The optimal degree of hormonal suppression is still unknown.
We hypothesized that in girls treated for CPP, estradiol levels (by ultrasensitive bioassay) would correlate with the rate of skeletal maturation and linear growth velocity. We asked whether predicted height would improve with greater luteinizing hormone (LH) and estradiol suppression. We also compared pre- and post-injection LH levels for monitoring treatment.
Thirty girls with CPP were followed for up to 2 years during treatment with leuprolide acetate depot at a dose of 0.3 mg/kg/28 days. We measured LH and estradiol levels, bone age, and growth velocity every 6 months.
Estradiol levels were suppressed to below the detection limit in three-quarters of the girls and did not correlate with the rate of skeletal maturation or linear growth. Improvement in predicted height correlated significantly with lower pre-injection LH levels. These girls have some of the lowest estradiol and LH levels, best improvement in predicted height, and least amount of bone age advancement published to date. Pre- and post-leuprolide injection LH levels were positively correlated.
Greater LH suppression may improve height outcome in girls treated for CPP with GnRH analogues. The degree of LH suppression achieved is individualized and not necessarily related to absolute dose. Pre-injection LH levels may be useful for monitoring treatment. Ultrasensitive estradiol levels were very low and usually unmeasurable, affirming the increased suppression at the higher doses of GnRH analogue used in these girls. Further investigation is needed, with longer treatment duration, a range of doses, and ultimately final height. Until such studies are completed, clinicians should be cautious when interpreting pubertal suppression.
中枢性性早熟（CPP）女孩采用促性腺激素释放激素（GnRH）类似物治疗以抑制青春期发育。由于低水平雌二醇难以测量，故使用促性腺激素水平来监测治疗。激素抑制的最佳程度仍不清楚。
我们推测，接受CPP治疗的女孩，其雌二醇水平（通过超敏生物测定法）与骨骼成熟速率和线性生长速度相关。我们探讨了促黄体生成素（LH）和雌二醇抑制程度越高，预测身高是否会改善。我们还比较了注射前后的LH水平以监测治疗效果。
30例CPP女孩接受醋酸亮丙瑞林缓释剂治疗，剂量为0.3mg/kg/28天，随访长达2年。每6个月测量LH和雌二醇水平、骨龄和生长速度。
四分之三女孩的雌二醇水平被抑制至检测限以下，且与骨骼成熟速率或线性生长无关。预测身高的改善与注射前较低的LH水平显著相关。这些女孩的雌二醇和LH水平是目前已发表研究中最低的，预测身高改善最佳，骨龄进展最少。注射亮丙瑞林前后的LH水平呈正相关。
更大程度的LH抑制可能改善接受GnRH类似物治疗的CPP女孩的身高结局。所达到的LH抑制程度是个体化的，不一定与绝对剂量相关。注射前LH水平可能有助于监测治疗。超敏雌二醇水平非常低，通常无法测量，这证实了在这些女孩中使用较高剂量GnRH类似物时抑制作用增强。需要进行进一步研究，包括更长的治疗时间、一系列剂量以及最终身高。在这些研究完成之前，临床医生在解释青春期抑制时应谨慎。
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