Endometrial safety of third generation aromatase inhibitors versus tamoxifen in breast cancer patients

The estrogenic activity of tamoxifen on the uterus increases the risk of developing benign and malignant uterine pathologies in breast cancer patients receiving this drug. This has led to gynecological interventions specifically in symptomatic women to exclude malignant disease. Given this known side effect associated with tamoxifen therapy, newer endocrine therapies such as the third-generation aromatase inhibitors have been compared to tamoxifen also in terms of their uterine effects. To date, studies that have directly compared the uterine effects of tamoxifen with that of aromatase inhibitors generally show that aromatase inhibitors such as anastrozole, letrozole, and exemestane are associated with less uterine pathologies compared to tamoxifen. Furthermore, aromatase inhibitors may even reverse uterine abnormalities induced by tamoxifen. This implies that the absence of a stimulatory effect on the uterus would be one of the benefits gained with aromatase inhibitor therapy and may decrease or even obviate the need for gynecological interventions.