RT Journal Article SR Electronic T1 Estradiol and oxytocin modulate sex differences in hippocampal reactivity and episodic memory JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.11.22.469500 DO 10.1101/2021.11.22.469500 A1 Marie Coenjaerts A1 Isabelle Trimborn A1 Berina Adrovic A1 Birgit Stoffel-Wagner A1 Larry Cahill A1 Alexandra Philipsen A1 René Hurlemann A1 Dirk Scheele YR 2021 UL http://biorxiv.org/content/early/2021/11/22/2021.11.22.469500.abstract AB Considerable evidence supports sex differences in autobiographical and episodic memory which may translate to heightened vulnerability to stress- and trauma-related disorders in women. The hormones estradiol and oxytocin both affect episodic memory, but possible sex-specific effects and hormonal interactions have not been systemically tested in humans. We conducted a randomized, placebo-controlled, parallel-group functional magnetic resonance imaging (fMRI) study involving healthy women (n = 111) and men (n = 115). Participants were scanned under four experimental conditions: 1. estradiol gel (2 mg) and intranasal oxytocin (24 IU), 2. placebo gel and intranasal oxytocin, 3. estradiol gel and placebo spray, 4. placebo gel and placebo spray. During fMRI, participants viewed positive, neutral and negative scenes. A surprise recognition task three days later was used to classify encoding trials as remembered or forgotten. 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. Separate treatments with either estradiol or oxytocin significantly diminished this mnemonic and hippocampal sex difference, whereas the combined treatment produced no significant effect. Collectively, our results suggest that estradiol and oxytocin 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.Competing Interest StatementThe authors have declared no competing interest.