Human Reproduction, Vol. 16, No. 9, 1838-1844,
September 2001
© 2001 European Society of Human Reproduction and Embryology
Hypothalamic–pituitary–ovarian dysfunction after prepubertal chemotherapy and cranial irradiation for acute leukaemia
1 Section of Child Life and Health, Department of Reproductive and Developmental Sciences, University of Edinburgh, 2 MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology and 3 Section of Obstetrics and Gynaecology, Department of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, UK
BACKGROUND: We assessed adult hypothalamic–pituitary–ovarian function following treatment with chemotherapy and cranial irradiation for childhood acute lymphoblastic leukaemia. METHODS: The patients (n = 12) had median age at diagnosis of 4.7 years, and at assessment of 20.8 years. They collected a daily urine sample over two to five consecutive menstrual cycles (total of 41 cycles) for analysis of LH and steroid excretion. Blood sampling and ovarian ultrasound examination was performed in the early follicular phase. Sixteen healthy women with regular menstrual cycles were recruited as controls. RESULTS: Urinary LH excretion was significantly lower in patients throughout the cycle, particularly during the LH surge (P < 0.0001). The length of the luteal phase was significantly shorter in patients than in normal controls (12.2 ± 0.3 versus 13.6 ± 0.4 days, P = 0.01) with a high prevalence of short (
11 days) luteal phases (15/39 cycles). Luteal phase pregnanediol excretion was slightly but not significantly lower. Follicular and luteal phase excretion of oestrone was lower in patients than in controls (P = 0.01). Early follicular phase plasma oestradiol was also lower in the patient group (P = 0.032) although LH, FSH, inhibin A and B concentrations were similar. CONCLUSIONS: These data indicate that treatment for childhood leukaemia results in subtle ovulatory disorder in some patients, probably related to cranial irradiation. Follow-up of these women is required to detect any effect on reproductive potential.
Key words: chemotherapy/leukaemia/ovary/pituitary/radiotherapy
4 To whom correspondence should be addressed at: MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, 37 Chalmers St., Edinburgh EH3 9ET, UK. E-mail: r.a.anderson{at}hrsu.mrc.ac.uk
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