来曲唑治疗特发性中枢性性早熟男童的临床观察

Clinical efficacy of letrozole in boys with idiopathic central precocious puberty

摘要:

目的 对骨龄大于13岁、身高偏矮小的中枢性性早熟（ICCP）男童应用来曲唑（letrozole）治疗，观察该治疗方案对延缓骨龄老化和改善成年预测身高的效果和不良反应。方法 将骨龄大于13岁的ICCP男童20例随机分为2组，每组10例，一组予来曲唑口服治疗6个月[2.5 mg/（m²·d），Qd]；另一组为对照组，定期观察，不予特殊治疗。观察两组男童骨龄、生长速度、身高标准差积分、预测成年身高标准差积分、性征发育情况及性激素水平的变化。并观察来曲唑治疗相关不良反应。结果 试验开始6个月后，来曲唑组和对照组男童骨龄均显著增加，但来曲唑组男童骨龄增长（13.82±0.23岁）较对照组男童（14.47±0.30岁）明显缓慢（P<0.05）；来曲唑组男童预测成年身高标准差积分（-1.69±0.26）较对照组（-1.91±0.35）显著升高（P<0.05）；来曲唑组男童睾酮水平（4.9±0.9 nmol/L）较对照组男童（4.4±0.8 nmol/L）显著升高（P<0.05）；睾丸容积在两组间差异无统计学意义；生长速度、阴毛分期、促卵泡刺激素、促黄体生成素、孕酮、雌二醇、雄烯二酮在两组间及治疗前后差异均无统计学意义。治疗过程中未见来曲唑治疗相关不良反应。结论 对骨龄超过13岁、身高受损显著的ICCP男童应用来曲唑能够有效减缓骨龄老化，改善预测成年身高，且未见明显不良反应。

Abstract:

Objective To investigate the efficacy of letrozole for delaying bone maturation and increasing predicted adult height in boys with idiopathic central precocious puberty (ICPP) who have a bone age above 13 years and a short stature, and its adverse effects. Methods Twenty ICPP boys with a bone age above 13 years and a short stature were randomly divided into letrozole treatment (n=10) and control groups (n=10). The letrozole treatment group received oral letrozole [2.5 mg/(m²·d), Qd] for 6 months, while the control group received no treatment and was observed periodically. Bone age, growth rate, height standard deviation (SD) score, predicted adult height SD score, sexual maturity, and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone, testosterone (T), estradiol (E2), progesterone (P), and androstenedione (ASD) were measured. The letrozole-related adverse reactions were evaluated. Results After 6 months of treatment, both groups had a significantly increased bone age, but the letrozole group had a significantly slowed increase in bone age compared with the control group (13.82±0.23 years vs 14.47±0.30 years; P<0.05); compared with the control group, the letrozole group had a significantly increased predicted adult height SD score (-1.69±0.26 vs -1.91±0.35; P<0.05) and a significantly increased T level (4.9±0.9 nmol/L vs 4.4±0.8 nmol/L; P<0.05). There was no significant difference in testicular volume between the two groups. The treatment led to no significant changes in growth rate, Tanner stage, and levels of FSH, LH, P, E2 and ASD in the two groups, and there was no significant difference in these indices between the two groups. No adverse reactions were observed during letrozole treatment. Conclusions Letrozole delays bone maturation and increases predicted adult height in ICPP boys with a bone age above 13 years and a short stature, and it causes no obvious adverse reactions.