Unopposed estrogen can cause endometrial carcinoma, particularly type I endometrioid endometrial carcinoma.

It first promotes endometrial hyperplasia, which can progress to carcinoma. This is why people with a uterus taking menopausal estrogen generally also need a progestogen for endometrial protection. The NCI endometrial guidance confirms that prolonged unopposed estrogen increases this risk.

Estrogen exposure is also associated with breast cancer risk, but the classic single-best-answer is endometrial carcinoma.