Prolactinomas, the most common type of pituitary tumor, can induce hyperprolactinemia and cause some psychiatric symptoms, such as anxiety, depression and even psychotic symptoms. However, in previous case reports, no information about estrogen levels was mentioned. Here, we present a 48-year-old female patient who had a recurrent episode of major depressive disorder (MDD) and amenorrhea. Hyperprolactinemia (167 ng/ml), low estrogen (15.31 pg/ml) and a pituitary prolactinoma were found by MRI. After a dopamine agonist (Dostinex) and aripiprazole were prescribed, the patient's depressed mood remitted and her menstruation normalized. The possible mechanism of MDD induced by prolactinoma is discussed.