van Beek Robert D, Smit Marij, van den Heuvel-Eibrink Marry M, de Jong Frank H, Hakvoort-Cammel Friederike G, van den Bos Cor, van den Berg Henk, Weber Rob F A, Pieters Rob, de Muinck Keizer-Schrama Sabine M P F
Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Room Sp3435, PO Box 2060, 3000 CB Rotterdam, The Netherlands.
Hum Reprod. 2007 Dec;22(12):3215-22. doi: 10.1093/humrep/dem313. Epub 2007 Nov 2.
The aim of this study was to evaluate the long-term gonadal sequelae after treatment for childhood Hodgkin's lymphoma with combination chemotherapy, using up to date fertility parameters and andrological evaluation, including for the first time inhibin B.
There were 56 male patients treated from 1974-1998 for childhood Hodgkin's lymphoma with combination chemotherapy ABVD or EBVD (adriamycin/epirubicin, bleomycin, vinblastine, dacarbazine) with or without MOPP (mechlorethamine, vincristin, prednisone, procarbazine) with the intention to avoid radiotherapy. These men were studied 15.5 years (range 5.6-30.2 years) after cessation of therapy. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, testosterone, sex hormone-binding globulin (SHBG), sperm concentration and sperm DNA integrity were determined.
In men treated with MOPP, median FSH and LH were significantly increased (P < 0.001) and inhibin B (17.5 versus 143 ng/l; P < 0.001) and sperm concentration (1.05 versus 49.5 x 10(6)/ml; P < 0.05) were significantly decreased compared with patients treated without MOPP. The number of MOPP courses was significantly correlated with FSH and inhibin B levels. Only inhibin B showed an independent correlation with sperm concentration (r = 0.86; P < 0.001).
The use of MOPP chemotherapy causes permanent gonadal damage in the far majority of male survivors of childhood Hodgkin's lymphoma and inhibin B is the most valuable serum marker for gonadal function.
本研究旨在利用最新的生育参数和男科评估，包括首次使用抑制素B，评估联合化疗治疗儿童霍奇金淋巴瘤后的长期性腺后遗症。
1974年至1998年期间，有56名男性患者接受联合化疗ABVD或EBVD（阿霉素/表柔比星、博来霉素、长春花碱、达卡巴嗪）治疗儿童霍奇金淋巴瘤，联合或不联合MOPP（氮芥、长春新碱、泼尼松、丙卡巴肼），目的是避免放疗。这些男性在治疗停止后15.5年（范围5.6 - 30.2年）接受研究。测定血清卵泡刺激素（FSH）、黄体生成素（LH）、抑制素B、睾酮、性激素结合球蛋白（SHBG）、精子浓度和精子DNA完整性。
与未接受MOPP治疗的患者相比，接受MOPP治疗的男性患者FSH和LH中位数显著升高（P < 0.001），抑制素B（17.5对143 ng/l；P < 0.001）和精子浓度（1.05对49.5×10⁶/ml；P < 0.05）显著降低。MOPP疗程数与FSH和抑制素B水平显著相关。只有抑制素B与精子浓度呈独立相关（r = 0.86；P < 0.001）。
MOPP化疗的使用在绝大多数儿童霍奇金淋巴瘤男性幸存者中导致永久性性腺损伤，抑制素B是性腺功能最有价值的血清标志物。
