Cyclophosphamide-induced disturbance of gonadotropin secretion manifesting testicular damage.
Gonadal function was evaluated in 23 men (aged 14.8-28.8 years) treated in childhood with cytotoxic drugs for a solid tumour. Group 1 (N = 14) had been treated with non-alkylating drugs only, while group 2 (N = 9) received the alkylating drug cyclophosphamide in addition (range 3.8-19.5 g/m2). Median age at the start of treatment was 4.6 years (range 0.6-16.1) in group 1 and 13.9 years (range 3.7-16.9) in group 2. Data of the patients were compared with a reference group consisting of 14 normal men. Almost all patients of both groups showed normal development of puberty; 13 of the 14 men in group 1 showed normal hormonal values. In group 2, basal LH and FSH as well as the LH and FSH responses to GnRH showed higher levels compared to those of a reference group (p less than 0.001). Correlation analysis showed an evident correlation between the total dose of received cyclophosphamide and the basal FSH level (r = 0.78; p = 0.002), the FSH response to GnRH (r = 0.73; p = 0.002) and the LH response to GnRH (r = 0.67; p = 0.002). There was no correlation between the hormonal parameters and the doses of the other cytotoxic drugs. Semen analysis showed azoospermia in four boys of group 2 and in none of group 1. Two patients in group 2 had an elevated FSH response to GnRH while their semen analysis was normal.


CONCLUSIONS
(1) There is a dose-response relationship between the basal FSH, the LH and FSH responses to GnRH and the dose of cyclophosphamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Hoorweg-Nijman
J J
JJ
Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
Delemarre-van de Waal
H A
HA
de Waal
F C
FC
Behrendt
H
H
D000293:Adolescent; D000328:Adult; D003520:Cyclophosphamide / Q000009:adverse effects*; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D011627:Puberty; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D012512:Sarcoma, Ewing / Q000188:drug therapy; D012661:Semen / Q000166:cytology; D013076:Sperm Count; D013733:Testicular Diseases / Q000139:chemically induced* / Q000473:pathology; D013737:Testis / Q000473:pathology; D009396:Wilms Tumor / Q000188:drug therapy
D007987:Gonadotropin-Releasing Hormone; D003520:Cyclophosphamide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone