Hypothalamic-pituitary-ovarian dysfunction after prepubertal chemotherapy and cranial irradiation for acute leukaemia.
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 (< or =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.
Bath
L E
LE
Section of Child Life and Health, Department of Reproductive and Developmental Sciences, University of Edinburgh, UK.
Anderson
R A
RA
Critchley
H O
HO
Kelnar
C J
CJ
Wallace
W H
WH
D000208:Acute Disease; D000328:Adult; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000652:urine; D005260:Female; D005498:Follicular Phase / Q000652:urine; D006728:Hormones / Q000097:blood; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007938:Leukemia / Q000188:drug therapy* / Q000532:radiotherapy*; D008183:Luteal Phase / Q000502:physiology; D007986:Luteinizing Hormone / Q000652:urine; D008597:Menstrual Cycle / Q000652:urine; D010053:Ovary / Q000503:physiopathology*; D011276:Pregnanediol / Q000652:urine; D011627:Puberty; D012016:Reference Values; D013997:Time Factors
D006728:Hormones; D004970:Estrone; D004958:Estradiol; D007986:Luteinizing Hormone; D011276:Pregnanediol