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) administrati on of tamoxifen citrate, 4-hydroxy tamoxifen, N-desmethyl tamoxifen and int ermittent oral tamoxifen administration on the fertility of the male rat an d its post reversal progeny. The fertility parameters of 120 day-treated ma le rat sires from all groups and post reversal male Fl 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 glan ds, serum luteinizing hormone, and testosterone levels without altering pot ency 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 i n the male rat. The antifertility effects of intermittent oral treatment we re more sustained than those of chronic oral tamoxifen treatment. It is inf erred that hepatic metabolism of tamoxifen interferes with its antifertilit y effects via oral route and that the parameters affected by chronic oral e xposure in the male sires are completely reversed in progeny ensuing after an adequate period of drug withdrawal. (C) 2001 Elsevier Science Inc. All r ights reserved.