Exogenous estradiol and oxytocin modulate sex differences in hippocampal reactivity and episodic memory

Abstract

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.

Investigation of whether oxytocin and trust play a role in placebo effects of marketing actions

“…Another limitation of our study is that we included only male participants. There is accumulating evidence that effects of intranasal OXT differ substantially between women and men 58 , which may be related to interactions between OXT and sex hormones such as estradiol 59 .…”

“…Another limitation of our study is that we included only male participants. There is accumulating evidence that effects of intranasal OXT differ substantially between women and men 58 , which may be related to interactions between OXT and sex hormones such as estradiol 59 . We focused on an exclusively male sample to increase the statistical power and to control for an additional source of noise due to potential gender-related (hormonal) differences of OXT effects on behaviour 58,60,61 .…”

Chronic Loneliness: Neurocognitive Mechanisms and Interventions

“…Both single-dose administrations of oxytocin and vasopressin may enhance the salience of social stimuli and decrease reactivity towards negative social feedback [150,151]. Although neuropeptide treatment effects in these domains may vary as a function of dosage [152,153], treatment expectation [154][155][156], and sex [157][158][159], the adjunct administration in combination with behavioral interventions may represent a promising venue to enhance the efficacy of loneliness interventions. Likewise, the endogenous oxytocin response to positive social interactions seems to be attenuated in high-lonely individuals [87], but repeated exposure to situations that have been found to induce the release of endogenous oxytocin such as massage, choir singing, or interpersonal synchronized behavior may reinstate normal neurohormonal responses [160][161][162].…”

Chronic loneliness: neurocognitive mechanisms and interventions

“…Both, single-dose administrations of oxytocin and vasopressin may enhance the salience of social stimuli and decrease reactivity towards negative social feedback [104,105]. Although neuropeptide treatment effects in these domains may vary as a function of dosage [106,107], treatment expectation [108][109][110], and sex [111][112][113], the adjunct administration in combination with behavioral interventions may represent a promising venue to enhance the efficacy of loneliness interventions.…”