Williams Denise, Crofton P M, Levitt Gill
Department of Paediatric Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Pediatr Blood Cancer. 2008 Feb;50(2):347-51. doi: 10.1002/pbc.21323.
Gonadal dysfunction and infertility are potential late effects of cancer therapy. Ifosfamide, an alkylating agent structurally related to cyclophosphamide, is thought to cause gonadal dysfunction, though there is little published evidence.
Patients treated on sarcoma protocols containing ifosfamide as the only potential gonadotoxic agent, were evaluated, assessing pubertal development, menstrual history in the females and semen analysis in males. Biochemical evaluation included measurement of gonadotrophins, inhibin B and anti-mullerian hormone (AMH).
All 32 males progressed normally through puberty. No gonadal dysfunction was seen at a total ifosfamide dose of <60 g/m(2). In those with a dose >60 g/m(2), two-thirds of those who underwent semen analysis were subfertile, 31% had elevated FSH and 50% showed decreased inhibin B supporting evidence of germ cell failure. All 13 females progressed through puberty normally and had regular menses. Biochemical results were in line with published data except for AMH levels, which were lower compared with an age-matched reference group. Nine patients not recruited into the study were known to have had 11 live births.
Males appear more susceptible than females to ifosfamide gonadotoxicity. There may be a dose in males below which the risk of subfertility is low. In females there is preliminary evidence of reduction in ovarian reserve as measured by AMH levels, which may potentially lead to an early menopause and a reduction in the window of fertility.
性腺功能障碍和不孕是癌症治疗潜在的晚期效应。异环磷酰胺是一种结构上与环磷酰胺相关的烷化剂，尽管鲜有公开证据，但被认为可导致性腺功能障碍。
对接受以异环磷酰胺作为唯一潜在性腺毒性药物的肉瘤治疗方案的患者进行评估，评估青春期发育情况、女性的月经史以及男性的精液分析。生化评估包括促性腺激素、抑制素B和抗苗勒管激素（AMH）的测定。
所有32名男性青春期发育正常。异环磷酰胺总剂量<60 g/m²时未观察到性腺功能障碍。在剂量>60 g/m²的患者中，接受精液分析的患者中有三分之二存在生育力低下，31%的患者促卵泡生成素（FSH）升高，50%的患者抑制素B降低，支持生殖细胞功能衰竭的证据。所有13名女性青春期发育正常且月经规律。除AMH水平外，生化结果与已发表的数据一致，与年龄匹配的参照组相比，AMH水平较低。已知9名未纳入该研究的患者有11次活产。
男性似乎比女性更容易受到异环磷酰胺性腺毒性的影响。男性可能存在一个低于此剂量时生育力低下风险较低的剂量。在女性中，有初步证据表明，以AMH水平衡量的卵巢储备减少，这可能会导致过早绝经并缩短生育期。
