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 interac-tions 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 bet-ter 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 treat-ments 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.

Automated summary

Considerable evidence supports sex differences in episodic memory. This study found that the hormones estradiol and oxytocin can modulate these sex differences, with separate treatments significantly reducing the differences and combined treatment having no effect. The results suggest the importance of these hormones in regulating sex differences in episodic memory, and possible antagonistic interactions between estradiol and oxytocin.