Tamoxifen antagonizes the effects of estradiol on energy balance and estrous behavior in Syrian hamsters.

Ovariectomized Syrian hamsters were treated with estradiol benzoate (5 micrograms/day for 4 wk), tamoxifen (500 micrograms/day), an antiestrogen that competes with estradiol for central and peripheral estrogen receptors, or both estradiol benzoate and tamoxifen. As expected, estradiol treatment caused significant decreases in body weight and fat content without affecting food intake. Given alone, tamoxifen had no effect on body weight or composition, but when given concurrently, tamoxifen significantly attenuated the effects of estradiol. These results stand in contrast to findings in rats where nonsteroidal antiestrogens, including tamoxifen, mimic the effects of estradiol on body weight and energy metabolism and are completely devoid of any antiestrogenic actions. As in rats, tamoxifen was a potent inhibitor of estrous behavior, whether induced with estradiol alone or with sequential treatment with estradiol and progesterone. Again, as in rats, tamoxifen acted as an antagonist and a weak estrogen agonist on uterine weight. These findings support the notion that the relative agonistic and antagonistic actions of tamoxifen, and other antiestrogens, vary with species and with the estrogen-sensitive endpoint being investigated.