Effects of tamoxifen on the fertility of male rats

Abstract

The effects of oral administration of tamoxifen (a synthetic non-steroidal anti-oestrogen) at doses of 40, 200 or 400 μg kg-1 day-1 on the circulating concentrations of LH, FSH, prolactin, testosterone and oestradiol, weights of pituitary, testes, secondary sex organs and the fertility of adult male rats were determined. The drug was administered per os daily, for up to 90 days. The fertility of rats treated with tamoxifen for 60, 70, 80 or 90 days was assessed by allowing them to mate with normal female rats of proven fertility. Tamoxifen at 40 μg kg-1 day-1 reduced concentrations of testosterone in plasma but had no affect on LH, FSH, prolactin and oestradiol concentrations, and the weights of pituitary, testes, epididymides, ventral prostate and seminal vesicles. Tamoxifen at 40 μg kg-1 day-1 reduced potency, fecundity, the number of implantation sites, the fertility index and litter size. Tamoxifen at 200 and 400 μg kg-1 day-1 reduced the concentrations of LH and testosterone in plasma and the weights of testes and secondary sex organs compared with controls. Tamoxifen at 400 μg kg-1 day-1 was most effective in reducing the number of viable pups, the litter size (≤ 1) and the fecundity (20%). The potency of treated rats (a measure of the presence of an ejaculate) was significantly decreased when compared with controls, but copulation was apparently not affected as mated female rats showed a constant dioestrous phase. Histology of the testes revealed disorganization of the cytoarchitecture of the tubules with obliterated lumen. All the parameters affected by tamoxifen at 200 μg kg-1 day-1 returned to normal values when tamoxifen was withdrawn for 90 days.