Does ifosfamide affect gonadal function?
BACKGROUND
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Williams
Denise
D
Department of Paediatric Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. denise.williams@addenbrookes.nhs.uks
Crofton
P M
PM
Levitt
Gill
G
D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects* / Q000627:therapeutic use; D007246:Infertility / Q000139:chemically induced; D008297:Male; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D012509:Sarcoma / Q000188:drug therapy / Q000503:physiopathology; D012737:Sex Factors; D013076:Sperm Count; D013737:Testis / Q000187:drug effects* / Q000469:parasitology
D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide