Aromatase inhibitors are generally not used to treat breast cancer in premenopausal women because, prior to menopause, the decrease in estrogen activates the
hypothalamus and
pituitary axis to increase
gonadotropin secretion, which in turn stimulates the ovary to increase
androgen production. The heightened gonadotropin levels also upregulate the aromatase promoter, increasing aromatase production in the setting of increased androgen
substrate. This would counteract the effect of the aromatase inhibitor in premenopausal women since total estrogen increased.