Estradiol and progesterone in female reward-learning, addiction, and therapeutic interventions

Sex steroid hormones like estradiol (E2) and progesterone (P4) guide the sexual organization and activation of the developing brain and control female reproductive behavior throughout the lifecycle; importantly, these hormones modulate functional activity of not just the endocrine system, but most of the nervous system including the brain reward system. The effects of E2 and P4 can be seen in the processing of and memory for rewarding stimuli and in the development of compulsive reward-seeking behaviors like those seen in substance use disorders. Women are at increased risk of developing substance use disorders; however, the origins of this sex difference are not well understood and therapeutic interventions targeting ovarian hormones have produced conflicting results. This article reviews the contribution of the E2 and P4 in females to functional modulation of the brain reward system, their possible roles in origins of addiction vulnerability, and the development and treatment of compulsive reward-seeking behaviors.