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Managing the side effects of tamoxifen

Suzanne D Conzen, MD
Section Editors
Daniel F Hayes, MD
William F Crowley, Jr, MD
Deputy Editor
Sadhna R Vora, MD


Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs) with both agonist and antagonist properties, depending on the individual target organ [1,2]. These differences are probably because of variable effects on gene expression in different cell types. (See "Mechanisms of action of selective estrogen receptor modulators and down-regulators".)

Both tamoxifen and raloxifene have antiestrogenic activity in breast tissue, reducing epithelial cell proliferation. This property has led to their clinical study as breast cancer chemopreventive agents. (See "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention".)

However, an important difference between the two drugs is their effect on the uterus, where tamoxifen has an estrogen-like effect while raloxifene acts as an estrogen antagonist. In apparent contrast to raloxifene, tamoxifen has been associated with endometrial hyperplasia [3,4], fibroids, polyps [4-6], and endometrial tumors (estrogen agonist effects) [7,8]. Tamoxifen is also associated with other side effects, including hot flashes (an estrogen antagonist effect), vaginal discharge, menstrual irregularities, sexual dysfunction, and blood clots. Although longer treatment with tamoxifen increases the risk of adverse effects, the reduction in breast cancer mortality associated with longer treatment outweighs those risks.  

This topic review will cover management of the major side effects of tamoxifen. The use of tamoxifen as a hormonal treatment for breast cancer, both in the adjuvant setting and for advanced disease, and the use of tamoxifen and raloxifene as chemopreventive agents in women at increased risk for breast cancer are discussed elsewhere. (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer" and "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention".)


Hot flashes are one of the most common and bothersome side effects of tamoxifen; they are believed to be due to a central nervous system antiestrogenic effect causing thermoregulatory dysfunction [9]. Up to 80 percent of women prescribed tamoxifen complain of hot flashes, and about 30 percent rate them as severe [10]. (See "Menopausal hot flashes".)

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Literature review current through: Nov 2017. | This topic last updated: Aug 10, 2017.
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