Sex steroid hormones are important regulators of reproductive function that affect not just the activity and morphology of peripheral gonadal tissue but are also synthesized in the central nervous system to organize and coordinate brain structure, activity, and subsequent behavioral responding within the environment. In females the major classes of ovarian sex steroids are estrogens (including estradiol or E2) and progestins (including progesterone or P4); these hormones are necessary for sexual differentiation of the fetal brain (González-Orozco and Camacho-Arroyo, 2019, Hutchison, 1999), modulate the development of numerous brain systems (Denley et al., 2018, Dickerson et al., 2011, Kipp et al., 2006), and interact with steroid hormone receptors throughout the central nervous system to modulate functional activity within. Because of this, a contemporary movement in neuroscientific research aims to increase the attention to and representation of female cells and animal models (McCullough et al., 2014; Sandberg et al., 2015), and from that body of research we now understand that in females E2 and P4 strongly modulate the brain reward system and, when disrupted, likely contribute to the development of neuropsychiatric disorders in women (Amin et al., 2006, Craig and Murphy, 2007, Österlund, 2002).

Learning of reward-associative information helps direct appropriate responding in the environment and is a necessary process to maintain our homeostatic needs and biological drives. Individual differences exist in reward learning and memory for reward-associated cues (Flagel et al., 2009, Flagel et al., 2008, Lesaint et al., 2014, Lovic et al., 2011, Robbins and Everitt, 1996); those differences can be attributed in part to the development of our brain reward system’s circuitry and the functional activity within that system (Flagel et al., 2007, Gallagher et al., 1990, Han et al., 1997, Sarter and Phillips, 2018). The neurobiology of reward learning relies in part on activity of dopamine (DA) cells that originate in the midbrain and project to various structures including the striatum, hippocampus, and prefrontal cortex (Routtenberg, 1978). In rodents and humans, females show increased sensitivity to rewarding stimuli and are subsequently at greater risk for developing compulsive reward-seeking behaviors such as those seen in substance use disorders (Greiner et al., 2019, Ruda-Kucerova et al., 2018, Tuchman, 2010); this relationship is strongly modulated by the hormonal status of the female learner (Becker and Hu, 2008, Carroll and Anker, 2010, Joyce et al., 2021, Lynch et al., 2002, Lynch and Sofuoglu, 2010). In the following sections the contribution of the primary ovarian sex steroid hormones E2 and P4 to female reward learning will be discussed with a focus on their modulation of the DA brain reward system, potential roots of sex differences in the development of compulsive reward-seeking behaviors, and as therapeutic targets.