In one study, the incidence of some tumours in hormone-dependent tissues was decreased, including in the mammary gland, although reduced weight gain may have been a contributing factor. In two studies in which tamoxifen was tested by subcutaneous implantation in intact or ovariectomized female mice, it inhibited mammary tumour development in both. In several studies in both male and female rats, tamoxifen enhanced the hepatocarcinogenicity of previously administered N -nitrosodiethylamine. In two studies in hamsters, tamoxifen inhibited hormonal carcinogenesis induced by 17 b -oestradiol in the kidney and zeranol in the liver. Tissue concentrations tend to be higher than plasma concentrations.
Metabolism involves phenyl hydroxylation, alkyl hydroxylation, demethylation and N -oxide formation.
Metabolism results in more products in man and rats than in mice. Much higher oral doses of tamoxifen are required for rats or mice to achieve plasma concentrations similar to human levels. This complexity is consistent with the various, and sometimes paradoxical, effects that have been associated with tamoxifen administration in animals and humans. The most frequent side-effects of tamoxifen administration are hot flushes and vaginal discharge. Tamoxifen has effects on the human uterus, inducing atrophy, hyperplasia and, less frequently, polyps.