Tumorigenic effects of tamoxifen on the female genital tract

Abstract

Tamoxifen is widely used for endocrine treatment and breast cancer prevention. It acts as both an estrogen antagonist in breast tissue and an estrogen agonist in the female lower genital tract. Tamoxifen causes severe gynecologic side effects, such as endometrial cancer. This review focuses on the effects of prolonged tamoxifen treatment on the human female genital tract and considers its tumorigenicity in the gynecologic organs through clinical data analysis. Tamoxifen is associated with an increased incidence of benign endometrial lesions such as polyps and hyperplasia and a two- to four-fold increased risk of endometrial cancer in postmenopausal patients. Moreover, the incidence of functional ovarian cysts is significantly high in premenopausal tamoxifen users. To prevent tamoxifen from having severe side effects in gynecologic organs, frequent gynecological examination should be performed for both premenopausal and postmenopausal patients with breast cancer who are treated with this drug.

Keywords: breast cancer; estrogenicity; ovary; tamoxifen; tumorigenicity; uterus.

Figure 1.

Molecular structure of tamoxifen.

Figure 2.

Pleiotropic effects of tamoxifen pointing to organ-specific beneficial or deleterious effects.

Figure 3.

Comparison of the two estrogen receptor molecules. The estrogen receptor consists of six functional domains. Estrogens manifest their biological activity through two distinct receptors, ERα and ERβ. The numbers in the boxes indicate numbers of amino acids. Homology between the distinct domains of the receptors is indicated. It is believed that the binding of different ligands induces structural alterations within the estrogen receptor and that the cells differ in their ability to recognize these conformations. TAF: transcription activating function.