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

Coenjaerts M, Adrovic B, Trimborn I, Philipsen A, Hurlemann R, Scheele D

Scientific reports22 Feb 2023Cited by 18 (Europe PMC)

PMID36813823PMCIDPMC9947123DOI10.1038/s41598-023-29754-yPepBankPUB-36813823

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

2 results from studies that gave the peptide. 2 results from people.

01HumanRandomized controlled trialEfficacy outcome
In healthy men, intranasal oxytocin decreased resting-state connectivity between the left amygdala and several visual and parietal regions versus placebo.
In plain wordsIn healthy men, oxytocin nasal spray lowered resting brain connectivity of the left amygdala with several regions compared with placebo.
Peptide
Oxytocin
Outcome
DecreaseAmygdala resting-state functional connectivity in men
Study
n = 116
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 IU · intranasalAs given in this study (human).
Source sentences
Summary
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
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3681382301
02HumanRandomized controlled trialEfficacy outcome
In healthy women, intranasal oxytocin alone increased resting-state connectivity between the right hippocampus and the left anterior cingulate gyrus.
In plain wordsIn healthy women, oxytocin nasal spray raised resting brain connectivity between the right hippocampus and the left anterior cingulate.
Peptide
Oxytocin
Outcome
IncreaseHippocampus resting-state functional connectivity in women
Study
n = 111
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 IU · intranasalAs given in this study (human).
Source sentences
Summary
In women, the single treatments significantly increased the rsFC between the right hippocampus and the left anterior cingulate gyrus
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3681382303

Studies that did not test the peptide alone3

In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Oxytocin.

03HumanNot a test of Oxytocin aloneRandomized controlled trialEfficacy outcome
In healthy men and women, treatments with oxytocin and estradiol had significant interaction effects with sex on amygdala and hippocampus connectivity.
In plain wordsIn healthy adults, the effects of oxytocin and estradiol on resting brain connectivity differed between men and women.
Peptide
Oxytocin
Outcome
MixedSex-by-treatment interaction on amygdala and hippocampus connectivity
Study
n = 227
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Source sentences
Summary
Our results reveal significant interaction effects of sex and treatments on rsFC of the amygdala and hippocampus in a seed-to-voxel analysis.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Oxytocin.
Show in the study text Report a problemFND-3681382305
04HumanNot a test of Oxytocin aloneRandomized controlled trialEfficacy outcome
In healthy men, oxytocin combined with estradiol increased resting-state connectivity of the amygdala, in contrast to the single treatments.
In plain wordsIn healthy men, oxytocin and estradiol given together raised resting brain connectivity of the amygdala, unlike either treatment alone.
Peptide
Oxytocin
Outcome
IncreaseAmygdala resting-state functional connectivity in men, combined treatment
Study
n = 116
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Source sentences
Summary
while the combined treatment produced a significant increase in rsFC.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Oxytocin.
Show in the study text Report a problemFND-3681382302
05HumanNot a test of Oxytocin aloneRandomized controlled trialEfficacy outcome
In healthy women, oxytocin combined with estradiol had the opposite effect on hippocampus connectivity from the single treatments.
In plain wordsIn healthy women, oxytocin and estradiol together had the opposite effect on resting brain connectivity from either treatment alone.
Peptide
Oxytocin
Outcome
DecreaseHippocampus resting-state functional connectivity in women, combined treatment
Study
n = 111
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Source sentences
Summary
whereas the combined treatment had the opposite effect.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Oxytocin.
Show in the study text Report a problemFND-3681382304

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 02:48 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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MeSH terms

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