Progestogens, such as megestrol acetate and medroxyprogesterone acetate, are effective at high doses in the treatment of advanced postmenopausal breast cancer. They have been extensively evaluated as a second-line therapy for this indication. However, they produce various side effects, such as dyspnea, weight gain, vaginal bleeding, nausea, fluid retention, hypertension, thrombophlebitis, and thromboembolic complications. In addition, megestrol acetate has been found to be significantly inferior to aromatase inhibitors in the treatment of breast cancer, and in relation to this, progestogens have been moved down in the sequential therapy of the disease. Megestrol acetate is the only Food and Drug Administration-approved progestogen for breast cancer. The mechanism of action of progestogens in the treatment of breast cancer is unknown, but may be related to their functional antiestrogenic and/or antigonadotropic effects.