Estrogen modulates inhibition of return in healthy human females.

Estrogen has a key role in explaining gender differences in dopaminergic functioning. To date, previous studies on estrogen have focused on inhibitory output control, such as the intentional suppression of overt pre-potent actions, but whether input control is also modulated is an open question. For the first time, this study compared the ability to perform a cued target-detection task that measured inhibition of return (IOR), a reflexive inhibitory mechanism that delays attention from returning to a previously attended location, in young women (n=21) across the three phases of their menstrual cycle (salivary estradiol and progesterone concentrations were assessed) and in young men (n=21). Women showed more pronounced IOR effect in their follicular phase, which is associated with both higher estradiol levels and higher dopamine turnover rates, than in their luteal or menstruation phase. This increase in women's IOR in their follicular phase was also greater than the effect found for men at any of the three phases. Our results are consistent with the idea that estrogen promotes IOR. Given that the mechanism underlying IOR biases the cognitive system towards the intake of novel information, our findings suggest that when the estrogen level is high, women are biased towards cognitive flexibility rather than cognitive stability. We conclude that gender differences in inhibitory input control are variable and state-dependent but not structural.