Hypothalamic-pituitary-ovarian dysfunction after prepubertal chemotherapy and cranial irradiation for acute leukaemia

BACKGROUND: We assessed adult hypothalamic-pituitary-ovarian function follo wing treatment with chemotherapy and cranial irradiation for childhood acut e 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 ova rian ultrasound examination was performed in the early follicular phase. Si xteen healthy women with regular menstrual cycles were recruited as control s. RESULTS: Urinary LH excretion was significantly lower in patients throug hout the cycle, particularly during the LH surge (P < 0.0001). The length o f the luteal phase was significantly shorter in patients than in normal con trols (12.2 +/- 0.3 versus 13.6 +/- 0.4 days, P = 0.01) with a high prevale nce of short (<less than or equal to>11 days) luteal phases (15/39 cycles). Luteal phase pregnanediol excretion was slightly but not significantly low er. 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 treat ment for childhood leukaemia results in subtle ovulatory disorder in some p atients, probably related to cranial irradiation. Follow-up of these women is required to detect any effect on reproductive potential.