Estradiol and progesterone interact with the dopaminergic and other neurotransmitter systems that are involved in the processing of rewards. On the systems level, these hormones modulate responses to stimulants as well as neuronal activity related to the anticipation of monetary gains. As different mechanisms might underlie the processing of gains and losses, the current study aims to investigate whether neural correlates of gain and loss anticipation are differentially modulated by menstrual cycle phases. Therefore, young, naturally cycling women were examined by means of functional neuroimaging during performing a modified version of the ‘Monetary Incentive Delay’ task in the early follicular and in the luteal menstrual cycle phase. During the low hormone early follicular phase, the anticipation of high vs. low gains and losses was associated with activity in a largely overlapping network of brain areas. However, high hormone levels in the luteal phase affected brain activity in these areas differentially during the anticipation of high vs. low gains and losses. In particular, the orbitofrontal cortex showed a reduced sensitivity to gain magnitude, whereas the ventral striatum and the anterior cingulate showed a reduced sensitivity to loss magnitude. In summary, the high amount of progesterone and estradiol in the luteal phase decreased activity related to the anticipation of monetary gains and losses in different brain areas, suggesting that hormones modulate different processes during the anticipation of gain and loss magnitude.