UCLA

Tamoxifen is a selective estrogen modulator used to treat breast cancer patients to reduce the reoccurrence of estrogen receptor-positive breast cancer. However, treatment with tamoxifen leads to serious side effects, including hot flashes. Hot flashes are a sudden feeling of warmth over the face, neck, and chest directly underneath the skin, but the mechanism of this thermal dysregulation is still unknown. Similar to what is observed in response to tamoxifen treatment, menopause is also associated with hot flashes. Menopausal hot flashes are thought to be caused by increased expression of neurokinin B in the infundibular (arcuate) nucleus of the hypothalamus. We hypothesized that a similar mechanism of increased neurokinin B expression might underlie tamoxifen-induced hot flashes. We compared neurokinin B expression in ovariectomized mice to control intact mice and intact mice treated with tamoxifen. Surprisingly, tamoxifen treatment in intact mice over the course of 10 days induces thermal dysregulation but decreases the expression of neurokinin B in the arcuate nucleus when compared to ovariectomized mice. These results indicate that a neurokinin B-independent mechanism of tamoxifen-induced thermal dysregulation exists.