Investigation of suppression of the hypothalamic–pituitary–gonadal axis to restore spermatogenesis in azoospermic men treated for childhood cancer

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.