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 > or =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 > or =12 weeks did not restore spermatogenesis in azoospermic men treated with gonadotoxic radiotherapy and chemotherapy for childhood cancer.
Thomson
A B
AB
Section of Child Life and Health, Department of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh EH9 1LW, Scotland, UK.
Anderson
R A
RA
Irvine
D S
DS
Kelnar
C J H
CJ
Sharpe
R M
RM
Wallace
W H B
WH
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D006066:Gonads / Q000187:drug effects*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D009369:Neoplasms / Q000628:therapy*; D009845:Oligospermia / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D011832:Radiation Injuries; D011944:Receptors, Androgen / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000473:pathology
D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D017258:Medroxyprogesterone Acetate