Effects of tamoxifen metabolites on fertility of male rat.
The effects of chronic oral administration of tamoxifen citrate, at a dose of 0.4 mg/kg/day, were compared to those of subcutaneous (s.c) administration of tamoxifen citrate, 4-hydroxy tamoxifen, N-desmethyl tamoxifen and intermittent oral tamoxifen administration on the fertility of the male rat and its post reversal progeny. The fertility parameters of 120 day-treated male rat sires from all groups and post reversal male F1 progeny of tamoxifen-treated sires were assessed. Chronic tamoxifen treatment via oral or s.c. routes reduced the fertility of the male rat, weights of accessory sex glands, serum luteinizing hormone, and testosterone levels without altering potency or sperm counts. However, antifertility effects of s.c. treatment were comparatively more consistent than those of oral treatment. 4-hydroxy and N-desmethyl tamoxifen failed to produce significant antifertility effects in the male rat. The antifertility effects of intermittent oral treatment were more sustained than those of chronic oral tamoxifen treatment. It is inferred that hepatic metabolism of tamoxifen interferes with its antifertility effects via oral route and that the parameters affected by chronic oral exposure in the male sires are completely reversed in progeny ensuing after an adequate period of drug withdrawal.
Gill-Sharma
M K
MK
Department of Neuroendocrinology, Institute for Research in Reproduction (ICMR), J.M.Street, Parel, Mumbai 400 012, India. dirirr@vsnl.com
Balasinor
N
N
Parte
P
P
Aleem
M
M
Juneja
H S
HS
D000284:Administration, Oral; D000818:Animals; D004958:Estradiol / Q000097:blood; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D005837:Genitalia, Male / Q000033:anatomy & histology; D007248:Infertility, Male / Q000139:chemically induced; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood
D013629:Tamoxifen; C016601:afimoxifene; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C028787:N-desmethyltamoxifen