Effects of exogenous oxytocin and estradiol on resting-state functional connectivity in women and men.

Possible interactions of the neuropeptide oxytocin and the sex hormone estradiol may contribute to previously observed sex-specific effects of oxytocin on resting-state functional connectivity (rsFC) of the amygdala and hippocampus. Therefore, we used a placebo-controlled, randomized, parallel-group functional magnetic resonance imaging study design and measured amygdala and hippocampus rsFC in healthy men (n = 116) and free-cycling women (n = 111), who received estradiol gel (2 mg) or placebo before the intranasal administration of oxytocin (24 IU) or placebo. Our results reveal significant interaction effects of sex and treatments on rsFC of the amygdala and hippocampus in a seed-to-voxel analysis. In men, both oxytocin and estradiol significantly decreased rsFC between the left amygdala and the right and left lingual gyrus, the right calcarine fissure, and the right superior parietal gyrus compared to placebo, while the combined treatment produced a significant increase in rsFC. In women, the single treatments significantly increased the rsFC between the right hippocampus and the left anterior cingulate gyrus, whereas the combined treatment had the opposite effect. Collectively, our study indicates that exogenous oxytocin and estradiol have different region-specific effects on rsFC in women and men and that the combined treatment may produce antagonistic effects.

Exogenous estradiol and oxytocin modulate sex differences in hippocampal reactivity during the encoding of episodic memories.

Considerable evidence supports sex differences in episodic memory. The hormones estradiol and oxytocin both affect episodic memory and may contribute to these sex differences, but possible underlying hormonal interactions have not been tested in a sample involving both sexes. To this end, we conducted a randomized, placebo-controlled, parallel-group functional magnetic resonance imaging (fMRI) study including healthy free-cycling women (n = 111) and men (n = 115). The fMRI session was conducted under four experimental conditions: 1. transdermal estradiol (2 mg) and intranasal oxytocin (24 IU), 2. transdermal placebo and intranasal oxytocin, 3. transdermal estradiol and intranasal placebo, 4. transdermal placebo and intranasal placebo. Participants were scanned during the encoding of positive, neutral, and negative scenes. Recognition memory was tested three days following the scanning sessions without additional treatments. Under placebo, women showed a significantly better recognition memory and increased hippocampal responses to subsequently remembered items independent of the emotional valence compared to men. The separate treatments with either hormone significantly diminished this mnemonic sex difference and reversed the hippocampal activation pattern. However, the combined treatments produced no significant effect. Collectively, the results suggest that both hormones play a crucial role in modulating sex differences in episodic memory. Furthermore, possible antagonistic interactions between estradiol and oxytocin could explain previously observed opposing hormonal effects in women and men.

Sex differences in economic decision-making: Exogenous estradiol has opposing effects on fairness framing in women and men.

Burgeoning evidence indicates that women are more sensitive to the context of an offer and show a stronger propensity to adjust their behavior with changing fairness frames. We evaluated whether the sex hormone estradiol and associated stereotypical beliefs contribute to fairness framings by administering topical estradiol (2 mg) to 108 healthy women and 104 heathy men in a randomized, double-blind, placebo-controlled between-subject study design. Participants played the role of the responder in a modified version of the Ultimatum Game (UG), in which identical offers for the division of a given amount of money were framed as either fair or unfair. Furthermore, participants completed an unframed UG and a delayed discounting task to probe possible effects of estradiol on altruistic preferences and delay gratification. Our results show that women were more sensitive to fairness frames than men. Intriguingly, however, estradiol had sex-specific effects on fairness sensitivity by increasing the acceptance rate of proposals with a fair frame in men and reducing it in women. Furthermore, the mere belief of receiving estradiol treatment significantly increased the acceptance of unfair-framed offers in both sexes, but estradiol did not significantly alter the response to unframed offers and impulsive decision-making. Collectively, our findings indicate that estradiol has opposing effects on the sensitivity to the perceived fairness of economic offers in women and men. The profound effects of estradiol treatment and stereotypical beliefs provide support for the notion that sex differences in fairness framing are rooted in both biological and environmental factors.