University Hospital of Cologne, Cologne, Germany.
J Clin Oncol. 2013 Jan 10;31(2):231-9. doi: 10.1200/JCO.2012.44.3721. Epub 2012 Nov 13.
To optimize fertility advice in patients with Hodgkin lymphoma (HL) before therapy and during survivorship, information on the impact of chemotherapy is needed. Therefore, we analyzed gonadal functions in survivors of HL.
Women younger than age 40 and men younger than 50 years at diagnosis in ongoing remission at least 1 year after therapy within the German Hodgkin Study Group HD13 to HD15 trials for early- and advanced-stage HL were included. Hormone parameters, menstrual cycle, symptoms of hypogonadism, and offspring were evaluated.
A total of 1,323 (55%) of 2,412 contacted female and male survivors were evaluable for the current analysis (mean follow-up, 46 and 48 months, respectively). Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels correlated significantly with therapy intensity (P < .001). Low birth rates were observed in survivors after advanced-stage treatment within the observation time (women, 6.5%; men, 3.3%). Regular menstrual cycle was reported by more than 90% of female survivors of early-stage HL (recovery time mostly ≤ 12 months). After six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, menstrual activity was strongly related to age (< v ≥ 30 years: 82% v 45%, respectively; P < .001; prolonged recovery time). Thirty-four percent of women age ≥ 30 years suffered severe menopausal symptoms (three- to four-fold more frequently than expected). In contrast, male survivors had mean levels of testosterone within the normal range and reported no increased symptoms of hypogonadism.
The present analysis in a large group of survivors of HL provides well-grounded information on gonadal toxicity of currently used treatment regimens and allows risk-adapted fertility preservation and comprehensive support during therapy and follow-up.
为了在治疗前和生存期间优化霍奇金淋巴瘤(HL)患者的生育咨询,需要了解化疗的影响。因此,我们分析了 HL 幸存者的性腺功能。
纳入在德国霍奇金研究组 HD13 至 HD15 试验中接受早期和晚期 HL 治疗、至少 1 年缓解且年龄在 40 岁以下的女性和 50 岁以下的男性。评估了激素参数、月经周期、性腺功能减退症状和后代。
共 2412 名有联系的女性和男性幸存者中,有 1323 名(55%)可用于当前分析(分别为平均随访 46 个月和 48 个月)。卵泡刺激素、抗苗勒管激素和抑制素 B 水平与治疗强度显著相关(P<0.001)。在观察期内,晚期治疗后的幸存者出生率较低(女性为 6.5%,男性为 3.3%)。大多数早期 HL 幸存者(恢复时间大多≤12 个月)报告月经周期规律。在博来霉素、依托泊苷、多柔比星、环磷酰胺、长春新碱、丙卡巴肼和泼尼松六个至八个周期后,月经活动与年龄密切相关(<v≥30 岁:分别为 82%和 45%;P<0.001;恢复时间延长)。34%的年龄≥30 岁的女性出现严重的更年期症状(比预期高三到四倍)。相比之下,男性幸存者的睾丸激素水平在正常范围内,且报告无性腺功能减退症状增加。
本研究对一大群 HL 幸存者进行了分析,为目前使用的治疗方案的性腺毒性提供了可靠的信息,并允许在治疗和随访期间进行风险适应的生育保护和全面支持。