Tamoxifen (TAM) is a selective estrogen receptor (ER) modulator that can alter the overall endocrine response. It is also an ER antagonist in breast cancer, being widely used in the treatment of this disease. Due to its undeniable success in the treatment and prevention of breast cancer in postmenopausal women, the prophylactic use of TAM for 5-10 years, has been proposed for premenopausal women, aiming the prevention/reduction of the disease. However, TAM therapy has several side effects associated with endocrine disruption at the neural, cardiovascular and systemic levels, and the risk/ benefit ratio of this preventive measure is still unknown. The liver and thyroid gland are important metabolic regulators with high endocrine modulation, making them preferential targets of systemic endocrine disruptors. Thus, to understand the effect of prolonged TAM therapy on endocrine regulation of metabolism, this project will study the liver and thyroid gland in premenopausal female rats using an animal model of long-term TAM. The studies of this project will able us to find answers to this current problem and help to outline new strategies in the prevention of breast cancer.