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抗苗勒管激素是治疗癌症的青春期前和青春期后女孩性腺毒性的标志物:一项前瞻性研究。

Anti-Müllerian hormone is a marker of gonadotoxicity in pre- and postpubertal girls treated for cancer: a prospective study.

机构信息

Department of Pediatric Hematology and Oncology, Royal Hospital for Sick Children, 17 Millerfield Place, Edinburgh EH9 1LF, United Kingdom.

出版信息

J Clin Endocrinol Metab. 2012 Jun;97(6):2059-67. doi: 10.1210/jc.2011-3180. Epub 2012 Apr 3.

Abstract

CONTEXT

Cytotoxic treatment may accelerate depletion of the primordial follicle pool, leading to impaired fertility and premature menopause. Assessment of ovarian damage in prepubertal girls is not currently possible, but Anti-Müllerian Hormone (AMH) is a useful marker of ovarian reserve in adults.

OBJECTIVE

The objective of the study was to prospectively evaluate AMH measurement in children as a marker of ovarian toxicity during cancer treatment.

DESIGN AND SETTING

This was a prospective, longitudinal study at a University Hospital.

PATIENTS

Twenty-two females (17 prepubertal), median age 4.4 yr (range 0.3-15 yr), were recruited before treatment for cancer.

MAIN OUTCOME MEASURES

AMH, inhibin B, and FSH at diagnosis, after each chemotherapy course and during follow-up, were measured. Risk of gonadotoxicity was classified as low/medium (n = 13) or high (n = 9) based on chemotherapy agent, cumulative dose, and radiotherapy involving the ovaries.

RESULTS

Pretreatment AMH was detectable across the age range studied. AMH decreased progressively during chemotherapy (P < 0.0001) in both prepubertal and pubertal girls, becoming undetectable in 50% of patients, with recovery in the low/medium risk groups after completion of treatment. In the high-risk group, AMH became undetectable in all patients and showed no recovery. Inhibin B was undetectable in most patients before treatment and, with FSH, showed no clear relationship to treatment.

CONCLUSION

AMH is detectable in girls of all ages and falls rapidly during cancer treatment in both prepubertal and pubertal girls. Both the fall during treatment and recovery thereafter varied with risk of gonadotoxicity. AMH is therefore a clinically useful marker of damage to the ovarian reserve in girls receiving treatment for cancer.

摘要

背景

细胞毒性治疗可能会加速原始卵泡池的耗竭,导致生育能力受损和早发性绝经。目前无法评估青春期前女孩的卵巢损伤,但抗缪勒管激素(AMH)是评估成年女性卵巢储备功能的有用标志物。

目的

本研究旨在前瞻性评估儿童 AMH 测量值作为癌症治疗期间卵巢毒性的标志物。

设计和设置

这是一项在大学医院进行的前瞻性、纵向研究。

患者

22 名女性(17 名青春期前),中位年龄 4.4 岁(范围 0.3-15 岁),在接受癌症治疗前入组。

主要观察指标

在诊断时、每次化疗后以及随访期间测量 AMH、抑制素 B 和 FSH。根据化疗药物、累积剂量和涉及卵巢的放疗,将性腺毒性风险分为低/中(n = 13)或高(n = 9)。

结果

在所研究的年龄范围内,均可检测到预处理 AMH。在青春期前和青春期女孩中,AMH 在化疗过程中逐渐下降(P < 0.0001),50%的患者 AMH 检测不到,低/中风险组在治疗完成后恢复。在高风险组中,所有患者的 AMH 均检测不到,且无恢复。在大多数患者治疗前抑制素 B 检测不到,与 FSH 一样,与治疗无明显关系。

结论

AMH 在所有年龄段的女孩中均可检测到,在青春期前和青春期女孩的癌症治疗过程中迅速下降。治疗期间的下降及其随后的恢复均与性腺毒性风险有关。因此,AMH 是评估接受癌症治疗的女孩卵巢储备功能损伤的一种有临床意义的标志物。

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