van Dorp W, van den Heuvel-Eibrink M M, de Vries A C H, Pluijm S M F, Visser J A, Pieters R, Laven J S E
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC-University Medical Centre Rotterdam's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Hum Reprod. 2014 Feb;29(2):337-42. doi: 10.1093/humrep/det442. Epub 2013 Dec 16.
Are anti-Müllerian hormone (AMH) levels reduced in girls with newly diagnosed cancer before the start of treatment?
AMH levels are already compromised in girls at the time of cancer diagnosis compared with healthy girls.
In women diagnosed with cancer, evidence of reduced ovarian function has been described even before treatment has started. In girls with newly diagnosed cancer, no data are available.
STUDY DESIGN, SIZE, DURATION: We performed an age-matched case-control study in girls with newly diagnosed cancer.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We determined serum AMH levels in a cohort of 208 girls with newly diagnosed cancer, up to 18 years of age at diagnosis, and compared them with AMH levels of 250 age-matched healthy girls. The diagnoses included were acute lymphoblastic leukaemia, acute myeloid leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, nephroblastoma, sarcoma and neuroblastoma.
The median age was 6.6 years (range 0.0-17.4), comparable with that in the control group (median 6.3 years, range 0.3-18.0). Girls with childhood cancer presented with significantly lower serum AMH levels compared with healthy age-matched controls (standard deviation scores (SDS) -0.8, P < 0.001). Median AMH level in patients was 1.4 μg/l (0.1-10.2) versus 3.0 μg/l (0.1-18.3) in controls. Specifically, 84% of all patients had AMH levels below the 50th percentile of normal AMH levels, and 19% below the 10th percentile. Surrogate markers of general health status (temperature, C-reactive protein and haemoglobin levels at diagnosis) were significantly correlated with AMH SDS.
LIMITATIONS, REASONS FOR CAUTION: Some caution is warranted because AMH levels increase with age in healthy children but the cases and controls were age-matched in our study. Although our sample size was large, additional studies are still required in an independent cohort.
Our study shows that AMH levels are reduced in girls with newly diagnosed cancer even before the cancer treatment has started. AMH levels correlate with impairment of general health status in girls. Therefore, besides (pre) antral follicle number, other factors may influence serum AMH levels. Longitudinal studies during and after childhood cancer are currently being performed in order to evaluate possible ovarian recovery after discontinuation of treatment.
STUDY FUNDING/COMPETING INTEREST(S): W.v.D. is supported by the Paediatric Oncology Centre Society for Research (KOCR), Rotterdam, The Netherlands. J.S.E.L. has received grants from the following companies (in alphabetical order): Ferring, Genovum, Merck Serono, Merck Sharp and Dome, Organon, Serono, Shering Plough and Shering. All other authors have nothing to disclose.
新诊断出癌症的女孩在开始治疗前抗苗勒管激素（AMH）水平是否降低？
与健康女孩相比，癌症诊断时女孩的AMH水平就已经受到影响。
在被诊断患有癌症的女性中，甚至在开始治疗之前就已经有卵巢功能降低的证据。对于新诊断出癌症的女孩，尚无相关数据。
研究设计、规模、持续时间：我们对新诊断出癌症的女孩进行了一项年龄匹配的病例对照研究。
研究对象/材料、地点、方法：我们测定了208名新诊断出癌症的女孩（诊断时年龄最大18岁）队列中的血清AMH水平，并将其与250名年龄匹配的健康女孩的AMH水平进行比较。诊断包括急性淋巴细胞白血病、急性髓细胞白血病、霍奇金淋巴瘤、非霍奇金淋巴瘤、肾母细胞瘤、肉瘤和神经母细胞瘤。
中位年龄为6.6岁（范围0.0 - 17.4岁），与对照组（中位年龄6.3岁，范围0.3 - 18.0岁）相当。与年龄匹配的健康对照组相比，患儿童癌症的女孩血清AMH水平显著降低（标准差分数（SDS）为 - 0.8，P < 0.001）。患者的中位AMH水平为1.4μg/l（0.1 - 10.2），而对照组为3.0μg/l（0.1 - 18.3）。具体而言，所有患者中84%的AMH水平低于正常AMH水平的第50百分位数，19%低于第10百分位数。一般健康状况的替代指标（诊断时的体温、C反应蛋白和血红蛋白水平）与AMH SDS显著相关。
局限性、谨慎原因：由于健康儿童的AMH水平随年龄增加，但我们的研究中病例和对照是年龄匹配的，所以需要一些谨慎。尽管我们的样本量很大，但仍需要在独立队列中进行额外研究。
我们的研究表明，新诊断出癌症的女孩在开始癌症治疗之前AMH水平就已降低。AMH水平与女孩的一般健康状况受损相关。因此，除了（前）窦卵泡数量外，其他因素可能会影响血清AMH水平。目前正在进行儿童癌症期间及之后的纵向研究，以评估治疗中断后卵巢功能的可能恢复情况。
研究资金/利益冲突：W.v.D. 得到荷兰鹿特丹儿科肿瘤中心研究协会（KOCR）的支持。J.S.E.L. 已从以下公司（按字母顺序排列）获得资助：辉凌、Genovum、默克雪兰诺、默克施贵宝、欧加农、雪兰诺、先灵葆雅和先灵。所有其他作者均无利益冲突需要披露。
