Tamoxifen associated uterine pathology in rodents: relevance to women

Abstract

Rats administered tamoxifen for 3 months and then returned to a basal diet developed an increase in uterine weight for up to 9 months after tamoxifen exposure. Stereological analysis of the tamoxifen exposed rat uteri showed that there was a significant increase in the amount of uterine myometrium, for a further 9 months, subsequent to the discontinuation of tamoxifen. A low incidence of myometrial proliferations (deciduomas) and uterine tumours was found at the conclusion of the study (20 months). In contrast, continuous administration of tamoxifen to mice for 24 months produced hyperplasia of the uterine endometrial epithelium and atrophy of the myometrium for the first 3 months, followed by atrophy of both the endometrium and myometrium for the remaining 21 months of the study. No uterine tumours were found in mice treated with tamoxifen for 2 years. The use of stereological analysis on interim sacrifice rodent uteri indicated that sustained uterine tissue compartment effects can occur, with either the continuous administration of tamoxifen, or after its discontinuation. Tamoxifen can have an agonist and antagonist like effect on oestrogen activity in different tissue compartments of the mouse uterus, over the same time period. The particular relevance of the finding of uterine proliferation and atrophy in the rodent studies with tamoxifen is discussed with regard to women taking this drug.