Falk Philip, Severin Mira, Berglund Åke, Guren Marianne G, Hofsli Eva, Österlund Pia, Tandberg Anne, Eberhard Jakob, Sorbye Halfdan
Department of Oncology, Skåne University Hospital, Lund, Backnejlikegatan 14, Kristianstad 29158, Sweden.
Department of Oncology, Skåne University Hospital, Lund, Backnejlikegatan 14, Kristianstad 29158, Sweden.
Cancer Treat Res Commun. 2022;31:100517. doi: 10.1016/j.ctarc.2022.100517. Epub 2022 Jan 20.
The incidence of colorectal cancer (CRC) in individuals of fertile age is increasing. Oxaliplatin is a cornerstone treatment in the adjuvant setting for stage III and high-risk stage II CRC. Limited data exist on possible side effects of oxaliplatin on fertility and gonadal function. More data is needed to guide possible fertility preservation procedures and aid evidence-based fertility counselling.
The aim of this study (EudraCT2006-002832-10) was to prospectively investigate sex hormones and sperm parameters after oxaliplatin-based adjuvant chemotherapy to clarify the risk of infertility and hypogonadism. Twenty males aged ≤55 years and 16 females aged ≤40 years were recruited from five hospitals in the Nordic countries. All had undergone radical surgery due to CRC and were given adjuvant oxaliplatin in combination with 5-fluorouracil. Measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG) and semen analysis were done in males, while LH, FSH and oestradiol were measured in females. Measurements were done prior to chemotherapy, after completion of adjuvant treatment and at follow-up 1 and up to 5 years after end of treatment.
FSH and testosterone levels increased in males after chemotherapy treatment but were restored at follow-up. No patients developed hypogonadism. There was a trend towards a decrease in sperm concentration during treatment (p = 0.063). When comparing sperm concentration and rapid progressive motility of sperms prior to chemotherapy and at follow-up, there were no differences, and no patients became permanently azoospermic by treatment. No distinct altering of gonadal function could be observed in females.
Oxaliplatin in combination with 5-fluorouracil seems to induce transient decrease in sperm concentration with recovery and a minor transient increase in FSH in males. No distinct altering of gonadal function was observed in females. The risk of infertility and hypogonadism in males and females after adjuvant oxaliplatin-based chemotherapy seems low.
育龄期个体患结直肠癌(CRC)的发病率正在上升。奥沙利铂是Ⅲ期和高危Ⅱ期CRC辅助治疗的基石。关于奥沙利铂对生育能力和性腺功能可能产生的副作用的数据有限。需要更多数据来指导可能的生育力保存程序,并为循证生育咨询提供帮助。
本研究(EudraCT2006 - 002832 - 10)的目的是前瞻性研究基于奥沙利铂的辅助化疗后的性激素和精子参数,以阐明不孕和性腺功能减退的风险。从北欧国家的五家医院招募了20名年龄≤55岁的男性和16名年龄≤40岁的女性。所有患者均因CRC接受了根治性手术,并接受了奥沙利铂联合5 - 氟尿嘧啶的辅助治疗。男性进行促黄体生成素(LH)、促卵泡生成素(FSH)、睾酮、性激素结合球蛋白(SHBG)的测定及精液分析,女性则测定LH、FSH和雌二醇。在化疗前、辅助治疗完成后以及治疗结束后1年至5年的随访期间进行测量。
化疗后男性的FSH和睾酮水平升高,但在随访时恢复正常。没有患者发生性腺功能减退。治疗期间精子浓度有下降趋势(p = 0.063)。比较化疗前和随访时的精子浓度及快速前向运动精子,无差异,且没有患者因治疗而永久性无精子症。在女性中未观察到性腺功能有明显改变。
奥沙利铂联合5 - 氟尿嘧啶似乎会导致男性精子浓度短暂下降并恢复,FSH略有短暂升高。在女性中未观察到性腺功能有明显改变。基于奥沙利铂的辅助化疗后,男性和女性发生不孕和性腺功能减退的风险似乎较低。