Comparison of the oestrogenic effects of infant milk formulae, oestradiol and the phytoestrogen coumestrol delivered continuously in the drinking water to ovariectomised mice

The potential oestrogenic effects of infant milk formulae, coumestrol and oestradiol delivered in the drinking water were investigated in ovariectomised mice. None of the infant formulae tested (three soya, two cowʹs milk) produced any uterotrophic or mitotic responses in the reproductive tract, although the soya milks displayed weak oestrogenic activity in vitro. Studies of the interactions between coumestrol and oestradiol were undertaken to investigate claims that phytoestrogens may act as oestrogen antagonists. The responses to coumestrol (100 μg/ml drinking water) and 17β-oestradiol (100 ng/ml) given separately were similar. Combined administration begun simultaneously produced only additive effects on uterine weight and cell proliferation in the vagina and uterus. While pretreatment with coumestrol for 24 h reduced the mitotic response of the uterus 48 h after placement of an oestradiol implant, the uterine weight increase was unaffected and the apparent reduction in mitoses reflected the natural fluctuations in the underlying cycle of cell proliferation. These studies indicate that coumestrol acts as a typical oestrogen and shows only additive effects with oestradiol. The results also indicate that infant soya milk formulae do not constitute a large enough source of oestrogenic compounds to invoke oestrogenic effects in the reproductive tract of mature mice.