Human Reproduction, Vol. 17, No. 7, 1715-1723,
July 2002
© 2002 European Society of Human Reproduction and Embryology
Investigation of suppression of the hypothalamic–pituitary–gonadal axis to restore spermatogenesis in azoospermic men treated for childhood cancer
1 Section of Child Life and Health, Department of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh EH9 1LW and 2 MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, Edinburgh EH3 9ET, UK
BACKGROUND: Does suppression of the hypothalamic–pituitary–gonadal (HPG) axis restore spermatogenesis in men rendered azoospermic following treatment of childhood cancer? METHODS: Seven men with azoospermia secondary to treatment for childhood cancer, median age (range), 22.2 (18–25.3) years, aged 10.4 (4.4–13.3) years at original diagnosis, participated. Each subject underwent semen analysis and testicular biopsy, followed by treatment with medroxyprogesterone acetate (MPA), 300 mg i.m. repeated after 12 weeks, with 800 mg testosterone pellets s.c. on day 1 to suppress the HPG axis. Hormone and semen analysis was performed every 6 weeks for 48 weeks. A second testicular biopsy was performed at week 48. RESULTS: Before HPG axis suppression, mean ± SEM plasma LH was 9.0 ± 1.8 U/l, testosterone 17.9 ± 1.5 nmol/l and FSH 22.4 ± 4.4 U/l. Median (range) venous plasma and seminal plasma inhibin B levels were 10.0 (7.8–35) and 11.2 (7.8–770) ng/l respectively. During HPG suppression, FSH and LH levels were undetectable for 
12 weeks followed by a gradual return to pretreatment concentrations by 48 weeks. All men remained azoospermic at study completion and complete absence of germ cells on biopsies was demonstrated by immunocytochemistry for all specimens pre- and post-HPG axis suppression. CONCLUSIONS: HPG axis suppression with MPA–testosterone for 12 weeks did not restore spermatogenesis in azoospermic men treated with gonadotoxic radiotherapy and chemotherapy for childhood cancer.
Key words: cancer/childhood/hormone suppression/spermatogenesis/testis
3 To whom correspondence should be addressed at: Department of Haematology/Oncology, Royal Hospital for Sick Children, 17 Millerfield Place, Edinburgh EH9 1LW, UK. E-mail: Hamish.Wallace{at}luht.scot.nhs.uk
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