Content uploaded by Nicoletta Cera
Author content
All content in this area was uploaded by Nicoletta Cera on Jun 11, 2021
Content may be subject to copyright.
REVIEW
How Relevant is the Systemic Oxytocin Concentration for Human
Sexual Behavior? A Systematic Review
Nicoletta Cera,
1,2
Sebasti
an Vargas-C
aceres,
3
C
atia Oliveira,
1,4,5
J
essica Monteiro,
2
David Branco,
2
Duarte Pignatelli,
6,7
and
Sandra Rebelo,
6,8,9
ABSTRACT
Introduction: Despite its role in social cognition and affiliative behavior, less is known about the role played by
oxytocin in human sexual behavior.
Aim: In the present systematic review, we aimed to find the levels of oxytocin related to human sexual arousal
and orgasm.
Methods: We conducted the study according to the PRISMA (Preferred Reporting Items for Systematic Reviews
and Meta-Analyses) guidelines. We performed a systematic search in the principal databases for studies that
reported collection of salivary or plasmatic samples, with dosage of oxytocin in relation to sexual activity during
induction of sexual arousal and orgasm.
Results: 414 articles were obtained. After duplicates removal and the application of pre exclusion criteria, 16
articles were considered eligible and 13 articles were included with a Cohen’s k of 0.827. Most of the studies
used sexual self-stimulation and collected plasmatic or salivary samples to measure oxytocin. The sexual arousal
and orgasm were assessed based on subjective reports.
Main Outcome Measure: The primary outcomes were the oxytocin levels collected during the induction of sex-
ual arousal and orgasm.
Conclusions: Several studies collected only subjective reports about the sexual arousal and the orgasm. Most of
the studies found higher levels of oxytocin during the orgasm or ejaculation. Given the sexual arousal evoked by
self-stimulation in which sexual fantasies play an important role, it should be possible to postulate for a role of
the oxytocin in sexual desire. In particular, we hypothesize a complex role of the oxytocin in the modulation of
sexual fantasies and thoughts that are relevant in the sexual desire and help to trigger genital and sexual arousal.
Copyright © 2021, International Society of Sexual Medicine. Published by Elsevier Inc. This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Key Words: Sexual Response; Orgasm; Oxytocin; Sexual Arousal
INTRODUCTION
During the last decades, the oxytocin attracted considerable
attention from the scientific community due to its role in several
cognitive and emotional functions.
1
Paraventricular and supra
optic nuclei of the hypothalamus synthesize the nonapeptide
oxytocin, which is transported in axons to the neurohypophysis,
where it is released into the blood circulation to reach remote and
peripheral locations.
2-4
Besides to its well-known roles in the stim-
ulation of the uterine tone and contractions during labor and in
milk ejection during lactation, it also plays an important role in
Received November 22, 2020. Accepted March 29, 2021.
1
CPUP- Center for Psychology at University of Porto, University of Porto,
Porto, Portugal;
2
Faculty of Psychology and Educational Sciences, University of Porto,
Porto, Portugal;
3
Mental Health Service, Benito Menni CASM, L’Hospitalet de Llobregat,
Barcelona, Catalonia, Spain;
4
Digital Human-Environment Interaction Lab, Lusofona University, Porto,
Portugal;
5
CUF Hospital, Porto, Portugal;
6
Department of BioMedicine, Faculty of Medicine, University of Porto,
Porto, Portugal;
7
Department of Endocrinology, Centro Hospitalar Universit
ario de S~
ao
Jo~
ao, Porto, Portugal;
8
Department of Clinical Pathology, Centro Hospitalar Universit
ario de S~
ao
Jo~
ao, Porto, Portugal;
9
Instituto de Investiga¸c~
ao e Inova¸c~
ao em Sa
ude (i3S), Universidade do
Porto, Porto, Portugal
Copyright © 2021, International Society of Sexual Medicine. Published by
Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://doi.org/10.1016/j.esxm.2021.100370
Sex Med 2021;9:100370 1
SEXUAL MEDICINE
the modulation of several cognitive and emotional functions most
importantly in creating maternal bonding.
5-7
Moreover, oxytocin
has been found to be important in the modulation of several
aspects of social behavior and in related pathological conditions. It
is well documented that oxytocin promotes social cohesion and
social contact between the individuals.
8-10
Indeed, alterations in
the level of oxytocin have been observed in borderline disorder,
autism spectrum disorders and anxiety.
11-13
As stated by Stoleru et al,
14
sexual behavior is a complex set of
components involving, at specific stages, several brain regions.
Sexual behavior and, more specifically, sexual arousal involves
autonomic, cognitive and emotional components. Among these,
the endocrine component is strongly affected by the cognitive
appraisal of the sexual stimulation. In this way, according to the
Stoleru’s hypothesis
14
the cognitive component would be impor-
tant to stimulate endocrine functions and the release of the sexual
and non-sexual hormones.
Evidences from animal studies showed that the administration
of oxytocin in the ventral tegmental area of the male rats induced
erection and the stimulation of receptors in the meso-limbic dopa-
minergic pathway was relevant for the reward and drive.
15
Interest-
ingly, IsHak et al
16
tested with good results intranasal oxytocin
administration in a case of male treatment-resistant anorgasmia. In
the same way, Muin et al,
17
in a Randomized, double-blind, pla-
cebo-controlled, crossover trial, involving pre and post −meno-
pausal women, the administration of intranasal oxytocin improved
over time sexual function. According to Georgiadis and Kringel-
back,
18
it is possible to frame the sexual behavior in a continuous
process consisting of three stages. The “cycle of pleasure”model
conceived sexual behavior as a process starting with the drive, fol-
lowed by excitation or arousal and orgasm, and inhibited by the
refractory periods or dysfunctions. The model relates the stages to
the activity in specific brain areas, representing an evolution of the
well-known model from Masters and Johnson.
19
The first stage of
the cycle implies a motivated, pro-sexual behavior, conceived as a
readiness status for sexual behavior. It has a different connotation
from the sexual desire, which represents a more complex process
relying on the same brain pathways important for sexual arousal
and sexual inhibition.
20
Moreover, sexual desire is sexual context
−independent.
21-23
Despite the knowledge that sexual development, reproductive
life and senescence are under the guidance of hormones, like oxy-
tocin, less is known about their relationship with specific stages
of the sexual arousal, desire and orgasm.
Consequently, we performed what we believe to be the first
systematic review about the role played by oxytocin levels (plas-
matic or salivary) in the male and female sexual behavior. In par-
ticular, we were interested in understanding (i) at which stages of
sexual behavior previous studies found higher levels of oxytocin.
(ii) Which is the best design and the best populations to study
the role played by oxytocin in human sexual behavior and (iii) if
the levels of oxytocin are related to subjective sexual arousal or to
genital sexual arousal.
METHODS
We used the approach recommended by the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines.
24
The computer-based literature searches follow the PICO
approach with combined terms related to oxytocin, sexual behav-
ior, sexual activity, and sexual function. In particular, our
research question was “What is the role played by the oxytocin
in sexual behavior as described in the evidence (O) in the healthy
population (P)?”The present review was limited to studies that
measured the level of oxytocin in body fluids, like saliva or blood
(I) during a task involving sexual activities (C). Table 1 shows
the search terms have been defined based on the PICO question
combined with the Boolean operators like “AND”,“OR”and
“NOT”, according to the method that has been previously used
in another systematic review.
25
We defined the inclusion and exclusion criteria based on the
topic, study design and population (Table 2). Most importantly,
concerning the population, we decided to exclude the studies in
which neuropsychiatric patients have been included (Table 2).
Studies about sexual dysfunctions has been included, given the
presence of different oxytocin levels in the patients group could
allow to disentangle its role in normal sexual behavior.
Table 2. Inclusion and exclusion criteria
Inclusion Criteria Exclusion Criteria
Experimental studies
Cross over repeated measure
studies
Cross sectional studies
Correlational studies
Randomized clinical trial
Intranasal oxytocin
Animals
Neuropsychiatric disease
Human Adults (>18 yr.)
Visual/audio sexual stimulation
Self-stimulation
Couple sexual activity
Table 1. Search strategy used in the current systematic review
Sexual Behavior/VSS
1. Sexual Behavior [Mesh]
2. Sexual activity
3. Sexual function [Title/Abstract]
4. Sexual arousal [Title/Abstract]
5. Visual sexual stimuli
6. Orgasm [Title/Abstract]
7. Ejaculation [Title/Abstract]
8. OR / 1-7
Study Design
12. Review [Publication
Type]
13. Systematic review
[Publication Type])
14. OR / 12-13
Oxytocin
9. Oxytocin [Title/Abstract]
10. Oxytocin [MeSH]
11. OR / 9-10
Combined search
15. #8 AND #11 NOT #14
2Cera et al
Sex Med 2021;9:100370
We performed the computer-based literature search in order
to retrieve all the published articles in English regarding the
above-mentioned topic. The three principal databases: MED-
LINE (PubMed), Scopus and Google Scholar were searched.
After the retrieval, all the studies included (see the inclusion
criteria) in the present systematic review were screened in order
to identify additional relevant bibliographic items. Moreover, the
narrative and systematic publications that were retrieved, but
considered off the topic for the outcome of the PICO, have also
been screened to find relevant studies cited in the reference lists.
After the duplicate removal, the title and abstracts were manu-
ally screened to understand if they fulfilled the inclusion and/or
exclusion criteria. After the retrieval of potentially relevant stud-
ies to be included, we read the full texts in order to confirm the
eligibility.
The first and second author performed independently the lit-
erature search, screening and methodological evaluation. The
consensus about the different stages was reached between the
two authors discussing the results and the articles retrieved. If the
consensus was not reached, a third opinion was obtained.
To assess the quality of the studies included in the present sys-
tematic review, we applied the “NIH/quality assessment tool for
before-after (pre-post) studies with no control group”and the
“Quality Assessment of Case-Control Studies”, following the
instructions (https://www.nhlbi.nih.gov/health-topics/study-
quality-assessment-tools;National Institutes of Health, 2014).
26
Information has been extracted from each included study, fol-
lowing the above-mentioned guidelines. In particular, we
extracted the characteristics of the participants, including the
exclusion and inclusion criteria.
RESULTS
Flowchart (Figure 1) showed the selection process of the stud-
ies. After the consensus was reached, 13 published studies have
been included in the systematic review. Following the guidelines
from Landis & Koch
27
we calculated Cohen's k with the 95 %
(k = 0.827) indicating almost perfect agreement (https://idostatis
tics.com/cohen-kappa-free-calculator/).
Tables 3 and 4show the principal characteristics of the stud-
ies. We selected studies published from 1969 until 2019. Most
of the included studies were conducted in different countries of
Europe (61.5%; n = 8) and 325 subjects have been enrolled in
the included studies. Most of the studies were crossover repeated
measure studies, only two were cross sectional, longitudinal case
control studies and only one a single case study. For this reason,
the quality assessment was based on two different checklists.
Tables 1S and 2S (supplementary information) showed the qual-
ity assessment of the included studies, by means of “NIH/quality
assessment tool for before-after (pre-post) studies with no control
group”and the “Quality Assessment of Case-Control Studies”,
performed by the two above-mentioned reviewers.
26
Radioimmunoassay (RIA) was used to determine the levels of
oxytocin in 61.5 % of the studies. In most of the cases, the
source of the oxytocin determinations has been plasmatic. Six
studies also measured other hormones in the collected samples,
namely cortisol, vasopressin and FSH, and LH (Table 4). Six
studies (46.5%) used clinical assessment, by means of tests, or
clinical interviews to evaluate several dimensions, like personal-
ity, anxiety and sexual functions of the participants enrolled.
Three studies used a multi-task approach in the same study, in
order to control confounding variables.
The studies did not show complete homogeneity and consis-
tency between results. This is congruent with the use of different
samples, tasks and experimental designs.
Among the retrieved studies, most of them examined the oxy-
tocin levels during orgasm and ejaculation. In the first published
study.
28
the authors showed, for the first time, the presence of
oxytocin in the plasma before and after an intercourse between
man and woman. Since the pioneer studies.
29-33
until the most
recent published one,
34
all of them showed an increase of the
oxytocin levels during, or immediately after, the orgasm or ejacu-
lation. The task used has been the sexual self-stimulation that
could be associated to visual sexual stimulation.
30-32,35
Interest-
ingly, most of the studies, assessing orgasm and ejaculation, did
not use psychophysiological measures, only based on subjective
reports. Carmichael et al
31,32
assessed pelvic contractions during
the arousal and orgasm by means of an anal device containing a
photoplethysmograph. Noteworthy, the authors reported
31,32
in
first study no significant differences between men and women
and, in the second one, significant positive correlations between
the systolic pressure, electromyography levels and oxytocin dur-
ing the baseline, arousal and orgasm or ejaculation. In the same
way, Kruger et al
35
assessed cardiovascular parameters (heart rate,
systolic and diastolic blood pressure) continuously during the
task. In particular, oxytocin showed a significant increase in the
orgasm in monorgasmic and multiorgasmic women. In multior-
gasmic women, the oxytocin level showed an increase between
the first and second orgasm.
31
Using a different methodological
approach, deJong et al
34
found an increase in oxytocin salivary
levels after 10 minutes of sexual self-stimulation in men and
women, without observing a specific gender effect. The studies
that used self-stimulation tasks (ie masturbation) showed the
highest levels of oxytocin in correspondence or after the orgasm
or ejaculation. Interestingly, comparing anorgasmic and orgasmic
women, Caruso et al
36
found that before and after the sexual
intercourse anorgasmic women showed lower oxytocin levels
than orgasmic ones. After coital activity, oxytocin levels did not
change in anorgasmic women, which experience unpleasant and
stressful sexual activity.
Despite the interest for the orgasm, three studies investigated
oxytocin levels during sexual arousal. Two of the three studies
involved women and used similar tasks. Alley et al,
37
studying
the oxytocin and cortisol levels during stress and sexual arousal
elicited by audio sexual stimulation, found a significant increase
Systemic Oxytocin and Sexual Behavior 3
Sex Med 2021;9:100370
in the oxytocin levels from baseline to arousal. Conversely, a sec-
ond study
38
found interesting results about oxytocinergic
involvement in the attention related processes of sexual arousal.
They found that women who were able to detect attentional
shifts and women who reported greater levels of sexual arousal
reported decrease in oxytocin in response to mindful breathing
and were the only women to report an increase in oxytocin in
response to sexual arousal induction. The study from Dickenson
et al
38
applied the Five-Facet Mindfulness Questionnaire
(FFMQ)
39
The third study investigated the relationship between genital
arousal and oxytocin in men. Moreover, the interest was about
the difference in oxytocin concentration in two different sites.
Uckert et al
40
collected the blood samples from cubital vein and
corpora cavernosa during the different stages of erection form
flaccid to rigidity during visual sexual stimulation and manual
stimulation of the gland. From flaccidity, considered as the base-
line, to tumescence oxytocin levels increased in both cubital vein
and corpora cavernosa, but from tumescent to rigidity, it
increased only in the corpora cavernosa. Indeed, the oxytocin
Figure 1. Flow diagram for identifying studies in the systematic review.
4Cera et al
Sex Med 2021;9:100370
levels recorded from the corpora cavernosa returned to the base-
line, but the levels of oxytocin recorded in the cubital vein did
not return to the baseline. Unfortunately, the authors did not
report the time in minutes, but they did only reported that the
blood collection was in correspondence of the detumescence.
Moreover, according to Salonia et al,
41
in normal cycling
women, oxytocin varied significantly during the menstrual cycle
with significant lower levels during luteal phase and correlated
with FSFI lubrification
42
. They found a significant correlation
between the oxytocin levels and both the FSFI arousal
42
Table 3. Demographic and psychometric tests applied in the included studies
Source Country N° subjects Men (%) Age (yr) Design
Psychological
assessment
Fox et al., 1969
28
UK 1 0(0) N/A Single case/crossover
study
N/A
Ogawa
et al., 1980
29
Japan 17 17(100) N/A
Patients with abnormal
spermatogenesis
Crossover study. N/A
Carmichael
et al. 1987
30
USA 22 9(40.9) 21-40 yr.
M: Mean = 28 §4 S.D.
W: Mean = 27.5 §4SD
Crossover study.
correlational study
Psychological
Interview
MMPI
BDI
Spielberger Manifest
Trait
Anxiety Test.
Murphy
et al.,1987
32
UK 13 13(100) 22-32 yr. Crossover study. N/A
Carmichael
et al. 1994
31
USA 23 10 (43.5) 21-40 yr.
M: Mean = 28
W: Mean = 27.5
Correlational study Psychological
interview
MMPI
BDI
Spielberger Manifest
Trait
Anxiety Test.
Blaicher
et al, 1999
33
Austria 12 0 (0) 23-37yr. Crossover study. Information from
clinical history
Kruger
et al., 2003
35
Germany 10 10 (100) 18-30 yr.
(Mean = 25.2
§1.21 S.D)
Crossover study. Semi-structured
interview; Physical
examination
SIS/SES
Uckert
et al., 2003
40
Germany 25 25(100) Mean = 26 yr. Crossover study N/A
Salonia
et al., 2005
41
Italy 30
(G1 = 20;
G2 = 10)
0(0) G1 : 21-43 yr. (Mean = 33.8)
G2 : 23-41 yr.(Mean = 32.4)
Cross-sectional study.
correlational study
Semi structured
interview (sexual
function and medical
history).
G1= normally cycling
fertile women
G2= monophasic
contraceptive pill
Caruso
et al., 2018
36
Italy 31
(G1 = 15;
G2 = 16)
0(0) G1: 25−34yr.;
Mean = 28.8 §5.7 S.D
G2: 24−35; Mean= 27.1 §
4.4 S.D .
Crossover study. SHI
FSFI;
FSDS
de Jong
et al., 2017
34
Germany 17 10(58.8) M:Median = 28yr., 26-65 yr.;
W: Median = 29 yr.;
23-52 yr.
Crossover study N/A
Alley et al., 2019
37
USA 63 0(0) 20-35 yr. Crossover study. N/A
Dickenson
et al., 2019
38
USA 61 0(0) 20-35 yr.; Mean = 27.2 yr. Crossover study. FFMQ
BDI = Beck Depression Inventory; FFMQ = Five Facet Mindfulness Questionnaire; FSDS = Female Sexual Distress Scale; FSFI = Female Sexual Function
Index; G = group; M = men; MMPI = Minnesota Multiphasic Personality Inventory; N/A = not available; SHI = sexual history interview; SIS/SES = System Inhi-
bition/System Excitation Scale; W = women; yr=years
Systemic Oxytocin and Sexual Behavior 5
Sex Med 2021;9:100370
Table 4. Tasks, hormonal assessment and Results described in the studies included in the systematic review
Source Task Hormonal assessment
Determination
of hormonal
levels Results
Fox et al.,
1969
28
Couple sexual activity Plasmatic oxytocin
and vasopressin
N/A Oxytocin was found in both cases in the blood
sample taken after female orgasm but no activity
was found in any of the samples from the male
or any of the controls.
Ogawa
et al.,
1980
29
Sexual self-stimulation Plasmatic oxytocin RIA Oxytocin levels increased significantly from 3.1§
1.9 pg/ml to 7.0 §4.5 pg/ml after ejaculation in
17 males (P<.01). No correlation with sperm
count.
Carmichael
et al.
1987
30
Sexual self-stimulation
continuing through
orgasm /ejaculation
Plasmatic oxytocin
collected 5 min.
before starting;
5min post
RIA Significant levels increase between baseline and
orgasm in men and monorgasmic women (P<
.05). Significant increase in Multiorgasmic W:
baseline =2 pg/ml; 1
st
orgasm= 2.7 pg/ml (P<
.03); 2
nd
orgasm=3.4 pg/ml; post orgasm=
3.4pg/ml.
Oxytocin self-stimulation = W: (3.4 pg/ml)>M:
(2.2 pg/ml; P<.05). Oxytocin orgasm = W: (4.4
pg/ml)>M: (2.5 pg/ml; P<.05)
Murphy
et al.,
1987
32
arousal induction task:
using fantasies
Plasmatic oxytocin
and vasopressin
RIA Oxytocin levels increased at the time of arousal
(ns) but increased with ejaculation; it increased
from a baseline of 1.4 §0.3 to 7.3 §2.6 pmol/L
(P<.01). The mean plasma level was still
significantly elevated 10 min after ejaculation,
reaching baseline in 30 min.
Carmichael
et al.,
1994
31
Sexual self-stimulation Plasmatic oxytocin
collected at
baseline, early SS,
mid SS, late SS,
orgasm and post
orgasm.
RIA Oxytocin levels increased from baseline through
the orgasm.
Blaicher
et al,
1999
33
Sexual self-stimulation Plasmatic oxytocin RIA Oxytocin level increased in each subject after 1
minute following the orgasm
(baseline = 11.53 pg/ml, 1 minutes after
orgasm=14.00 pg/ml; P= .0033); Level after 5
Minutes =12.56 pg/ml.
Kruger
et al.,
2003
35
Sexual self-stimulation;
visual sexual
stimulation
Plasmatic oxytocin,
epinephrine,
norepinephrine,
vasopressin,
prolactin, FSH, LH,
testosterone and
cortisol.
IRMA-
oxytocin
Orgasm produced an increase in oxytocin plasma
levels, which returned to basal values 10 min
after orgasm.
However, due to a large interindividual variance
these alterations did not reach statistical
significance (F(10,80)= 183, P= .068).
Uckert
et al.,
2003
40
Sexual self-stimulation
only in the glans; visual
sexual stimulation
Plasmatic oxytocin RIA Two subjects feel pain during data collection; Two
subjects did not terminate the experiment.
Oxytocin plasma levels increased in the systemic
and cavernous blood at the beginning of sexual
arousal during penile tumescence (Corpus
Cavernosum: from 66.7 §34 to 75 §44 pg/ml;
Cubital Vein: from 71 §41 to 79 §49.5 pg/ml).
Level of oxytocin increased during rigidity in the
cavernous blood (to 81 §58.2 pg/ml), but
unaltered in the systemic circulation (to 76.4 §
44 pg/ml). Increase in the systemic blood (to
94§49 pg/ml).
(continued)
6Cera et al
Sex Med 2021;9:100370
(P= .04; r= 0.72) and the lubrification
42
(P= .009; r= 0.84) in
women under treatment with estroprogestinic oral contracep-
tives, during the last week of treatment. Carmichael et al,
31
also
reported an increase of oxytocin levels during luteal phase, but
they did not observe a relationship between menstrual phases
and orgasm for oxytocin.
To check the quality of the selected studies, we assessed
how many of them reported the level of oxytocin after the
task. This is important from a methodological point of view
to know if the baseline is recovered after the task. Moreover,
this information can help to establish future practices in
studies that aim to collect hormonal data during an experi-
mental session. Most of the studies (ten, 76,9%) reported
the collection of samples to assess the return to the baseline
of oxytocin after the tasks. Five (38,5%) studies indicated
that blood or salivary samples having been collected after a
period of time of 10-20 minutes following the task or the
orgasm having been reached by the participants (Table 5).
DISCUSSION
Despite the relevance of the oxytocin in the social cognition
and emotions, a limited number of studies investigated the role
played by the oxytocin levels in human sexual behavior. The
present systematic review took into account only studies that
assessed the oxytocin levels without considering the randomized
Table 4. Continued
Source Task Hormonal assessment
Determination
of hormonal
levels Results
Salonia
et al.,
2005
41
N/A Plasmatic oxytocin
and other hormones.
RIA Oxytocin levels correlated with the FSFI-lubrication
subscale during the luteal (P= .007; r= 0.69)
phase. Oxytocin correlated with both the arousal
(P= .04; r= 0.72) and the lubrication (P= .009;
r= 0.84) scales as measured with FSFI during
the last week of assumption of the
estroprogenistic pill. No significant difference
among the mid luteal and mid follicular in FSFI.
Caruso
et al.,
2018
36
Couple sexual activity Plasmatic oxytocin ELISA At baseline, anorgasmic women showed lower
levels of oxytocin than orgasmic women, 1.8 §
0.2 pg/mL versus 2.1 §0.5 pg/mL, respectively
(P<.04). At T1, anorgasmic women showed
similar baseline levels of oxytocin. Orgasmic
women had higher level of oxytocin than
anorgasmic women, (P<.001).
de Jong
et al.,
2017
34
Run, breastfeeding and
sex tasks (ROC test):
sexual self-stimulation
Salivary oxytocin RIA 10-min of sexual self-stimulation caused an
increase inoxytocin levels (P<.001). Post-hoc
comparisons revealed a significant increase of
oxytocin concentrations 10 min after the start of
sexual self-stimulation (P≤.001). No difference
after 40 minutes (P= .438).
Alley et al.,
2019
37
audio sexual stimulation:
arousal induction task
Salivary oxytocin and
cortisol
EIA No differences in oxytocin levels in response to the
arousal task (mean difference = 0.18, t = 0.09,
P= .94). Participants showed a significant
increase in oxytocin from baseline to task for the
arousal assessment (b = 0.11, P= .02), but no
significant change from task to either the first
recovery (b = 0.02, P= .87) or the second
recovery (b = 0.10, P= .46).
Dickenson
et al.,
2019
38
audio sexual stimulation:
arousal induction task
Salivary oxytocin and
cortisol
EIA Significant random effect (P<.001), indicating
that women varied in the extent to which
oxytocin changed in response to the sexual
arousal induction. No significant change in
response to the sexual arousal induction (P>.1).
None of the facets of trait mindfulness (FFMQ)
moderated the change in oxytocin in response to
the sexual arousal induction (P>.2).
EIA= Enzyme immunoassay method; ELISA= Enzyme-linked immunosorbent assay; FSH=Follicle Stimulating Hormone; G= group; IRMA= Immuno radio-
metric assay; LH= Luteinizing Hormone; M= Men; RIA= Radioimmunoassay; SS= sexual stimulation; W= Women
Systemic Oxytocin and Sexual Behavior 7
Sex Med 2021;9:100370
clinical trials in which the administration of synthetic oxytocin
took place. Given the level of invasiveness of the procedure of
collection of the oxytocin, several studies collected only subjec-
tive reports about the sexual arousal and the orgasm.
28−38,40,41
In this way, given the subjective reports, it was not possible to
quantify the intensity or the exact moment in which sexual
arousal and orgasm occurred. Previous studies used psychophysi-
ological techniques to record the variation of the penile circum-
ference and vasocongestion of the vaginal wall during tasks like
visual sexual stimulation.
43
Carmichael et al,
10
in their pioneer
study, recorded the muscle activity in the pubic area by mean of
the recording of the anal blood-pulse amplitude and electromyo-
graphic activity that could be conceived as indirect measures of
genital arousal but could also be useful to record pelvic contrac-
tion during orgasm.
Our first aim concerned the stage of sexual behavior in which
the reviewed studies found higher levels of releasing oxytocin.
Most of the studies found higher levels, or at least peaks of oxyto-
cin levels during the orgasm or ejaculation.
28-38
Overall, this seems
to be confirmed by indirect evidence about women affected by
anorgasmia that showed lower levels than orgasmic women.
36
Oxytocin is the hormone responsible for the uterine contractions
during the labor
44,45
and it should be conceivable that a similar
contractile mechanism during the orgasm is able to release, at the
level of the neurohypophysis, higher amount of oxytocin. The role
of oxytocin in the ejaculation has been investigated in pharmaco-
logical animal studies,
46
showing contradictory results in shorten-
ing or prolonging the latency of the ejaculation.
47
Also in a
randomized, double-blind, placebo controlled study in men with
premature ejaculation, high doses of Cligosiban, an oxytocin
receptor antagonist, did not prolong the time of vaginal coitus and
the latency of intravaginal intercourse.
48
In this way, oxytocin
might not play a direct role in the latency of the erection needed
to a satisfactory intravaginal intercourse.
Importantly, reviewing these studies, we are able to hypothesize
that besides to the effect in the orgasm, oxytocin also plays a role in
the sexual arousal as confirmed by Alley et al
38
who observed a sig-
nificant change between the baseline and arousal during an audio
sexual stimulation task in 63 participants. Similarly, Uckert
40
found
an increase of oxytocin levels in the corpora cavernosa during the
tumescence that could reasonably be used as an index of genital
arousal. Despite this, the self-stimulation task appears to include a
series of sexual fantasies that represent uncontrollable confounding
variables, given their level of subjectivity. In this way, responding to
our second aim, one of the best options should be the use of a stan-
dardized audio and/or visual stimulation task in which it is possible
to minimize the effect of uncontrollable confounding variables. At
the same time, sexual fantasies, which are considered relevant for
sexual desire, can be the trigger for the sexual arousal and orgasm.
According to our review and the results obtained in the selected
studies, it should be plausible that a mechanism involving empathy
and reward could play an important role in these two stages of sex-
ual behavior. Indeed, the studies that used self-stimulation tasks
could confirm the hypothesis that sexual desire is a more complex
process that goes beyond sexual arousal and orgasm, and it is differ-
ent from the sexual drive needed to start sexual behavior.
23
Oxyto-
cin is primarily produced in the neurohypophysis and, so, a more
central mechanism related to sexual or romantic interaction could
be hypothesized. In this way, several studies highlighted its role in
prosocial and positive emotions.
49,50
In particular, oxytocin is
important for the neuroendocrine mediation of the romantic love
51
playing a role in the processes related to the initial stages of the
romantic passion.
52
This involvement could be explained in the
light of the role played by the oxytocin in empathy, in the reward
for positive social interaction
53-55
and the bonding creation.
Not all the studies, with the exception of Carmichael et al,
30,31
collected psychophysiological data, but only subjective ratings of sexual
arousal (our third aim). Overall, according to the obtained informa-
tion, the sexual arousal was not assessed with a Likert-like scale, but
the participants indicated the exact time in which it occurred. Several
studies showed that women’subjective experiences of arousal are not
automatically related to genital changes overall when the vaginal pulse
amplitude is assessed
56
. Despite the self-detection of the sexual arousal
could be easier in the male participants, women showed higher con-
centration levels of oxytocin than men as described by Marazziti et al.
57
In summary, the present systematic review was not able to
give a definitive response, in particular to determine the contri-
bution of oxytocin in female sexual arousal. Indirectly, Uckert,
37
reporting the values of the oxytocin during the penile tumescence
allowed a better understanding of the complex role of the oxyto-
cin in male sexual arousal.
CONCLUSIONS
Taking into account the limited number of studies that we were
able to collect about the oxytocin levels during the different stages
Table 5. Assessment of oxytocin baseline-recovery after tasks
Source Time in minutes
Fox et al., 1969
28
N/A
Ogawa et al., 1980
29
N/A
Carmichael et al. 1987
30
5
Murphy et al.,1987
32
30
Carmichael et al. 1994
31
5
Blaicher et al, 1999
33
5
Kruger et al., 2003
35
10
Uckert et al., 2003
40
N/A*
Salonia et al., 2005
41
N/A**
Caruso et al., 2018
36
5
de Jong et al., 2017
34
40**
Alley et al., 2019
37
20
Dickenson et al., 2019
38
15-20
*
Uckert et al. collected blood samples after detumescence;
**
correlational study; ***40 minutes from the onset of the stimulus and 10
after orgasm.
8Cera et al
Sex Med 2021;9:100370
of human sexual arousal, and the heterogeneity in the tasks and
population, our hypotheses have to be considered with caution.
However, the present systematic review highlighted the state
of the art of the studies that assessed the role played by the oxyto-
cin levels during the different stages of sexual behavior and, in
particular, during sexual arousal and orgasm in men and women.
In this way, thanks to the results here reported and described,
several hypotheses about the role of oxytocin in the attraction,
sexual fantasies and positive thoughts, plausibly regarding sexual
interaction and intercourse could play an important role in the
sexual arousal and in the genital response. To disentangle the
role played by the oxytocin in the sexual desire, arousal and
orgasm, further studies will be needed in which it should be
important to better control the possible confounding variables,
define the genital arousal and obtain a precise self-assessment of
the sexual arousal as well as the orgasm timing.
According to our review, the future investigation in the area of
the relations between the endocrine and the cognitive compo-
nents underlying human sexual behavior can be promising.
Corresponding Author: Nicoletta Cera, PhD, Faculty of Psy-
chology and Educational Sciences, University of Porto, Rua
Alfredo Allen, 4200-135 Porto, Portugal, Tel: +351 22 607
9700; E-mail: cera.nicoletta@gmail.com
Conflict of Interest: The authors report no conflicts of interest.
Funding: This study was funded by the Portuguese Science
Foundation (Grant number: FCT-PTDC/PSI-GER/30520/
2017; NORTE-01-0145-FEDER-030520).
STATEMENT OF AUTHORSHIP
Conceptualization, N.C. and S.V.C.; Methodology, N.C., S.
V.C and C.O.; Investigation, N.C., S.V.C, J.M. and D.B.; Writ-
ing −Original Draft, N.C. and S.V.C.; Writing −Review &
Editing, D. P. and S.R.; Funding Acquisition, N.C, C.O., J.M.
and D.P.; Supervision, D. P. and S.R.
REFERENCES
1. Heinrichs M, von Dawans B, Domes G. Oxytocin, vasopressin,
and human social behavior. Front. Neuroendocrinol.
2009;30:548–557.
2. Carter CS. Oxytocin and sexual behavior. Neurosci & Biobe-
hav Reviews 1992;16:131–144.
3. Carter CS. Sex differences in oxytocin and vasopressin: impli-
cations for autism spectrum disorders? Behav. Brain Res.
2007;176:170–186.
4. Carter CS. Oxytocin pathways and the evolution of human
behavior. Annu. Rev. Psychol. 2014;65:17–39.
5. Meinlschmidt G, Heim C. Sensitivity to intranasal oxytocin in
adult men with early parental separation. Biol. Psychiatry
2007;61:1109–1111.
6. Kendrick KM, Keverne EB, Baldwin BA. Intracerebroventricu-
lar oxytocin stimulates maternal behaviour in the sheep. Neu-
roendocrinology 1987;46:56–61.
7. Porter RH, Duchamp G, Nowak R, et al. Induction of maternal
behavior in non-parturient adoptive mares. Physiol. Behav.
2002;77:151–154.
8. Spengler FB, Scheele D, Marsh N, et al. Oxytocin facilitates
reciprocity in social communication. Social Cognitive and
Affective Neuroscience 2017;12:1325–1333.
9. Xu L, Becker B, Kendrick KM. Oxytocin facilitates social learn-
ing by promoting conformity to trusted individuals. Frontiers
in Neuroscience 2019;13:56.
10. Young LJ, Flanagan-Cato LM. Editorial comment: oxytocin,
vasopressin and social behavior. Horm. Behav. 2012;61:227.
11. Sasaki T, Hashimoto K, Oda Y, et al. Decreased levels of
serum oxytocin in pediatric patients with attention deficit/
hyperactivity disorder. Psychiatry Res. 2015;228:746–751.
12. Br€
une M. On the role of oxytocin in borderline personality dis-
order. Br. J. Clin. Psychol. 2016;55:287–304.
13. Scheele D, Kendrick KM, Khouri C, et al. An oxytocin-induced
facilitation of neural and emotional responses to social touch
correlates inversely with autism traits. Neuropsychopharma-
cology 2014;39:2078–2085.
14. Stol
eru S, Fonteille V, Corn
elis C, et al. Functional neuroimag-
ing studies of sexual arousal and orgasm in healthy men and
women: a review and meta-analysis. Neurosci & Biobehav
Reviews 2012;36:1481–1509.
15. Melis MR, Melis T, Cocco C, et al. Oxytocin injected into the
ventral tegmental area induces penile erection and increases
extracellular dopamine in the nucleus accumbens and para-
ventricular nucleus of the hypothalamus of male rats. Eur. J.
Neurosci. 2007;26:1026–1035.
16. IsHak WW, Berman DS, Peters A. Male anorgasmia treated
with oxytocin. J. Sex. Med. 2008;5:1022–1024.
17. Muin DA, Wolzt M, Marculescu R, et al. Effect of long-term
intranasal oxytocin on sexual dysfunction in premenopausal
and postmenopausal women: a randomized trial. Fertil. Steril.
2015;104:715–723.
18. Georgiadis JR, Kringelbach ML. The human sexual response
cycle: brain imaging evidence linking sex to other pleasures.
Prog. Neurobiol. 2012;98:49–81.
19. Masters WH, Johnson VE. Human Sexual Response. Little,
Brown.; 1966.
20. Pfaus JG. Reviews: pathways of sexual desire. The j. of sexual
med 2009;6:1506–1533.
21. Laan E, Both S. What makes women experience desire? Femi-
nism & Psychol 2008;18:505–514.
22. Brotto LA. The DSM diagnostic criteria for hypoactive sexual
desire disorder in women. Arch. Sex. Behav. 2010;39:
221–239.
23. Goldey KL, van Anders SM. Sexual arousal and desire: interre-
lations and responses to three modalities of sexual stimuli.
The j. of sexual med 2012;9:2315–2329.
Systemic Oxytocin and Sexual Behavior 9
Sex Med 2021;9:100370
24. Moher D, Liberati A, Tetzlaff J, Prisma Group. Reprint—pre-
ferred reporting items for systematic reviews and meta-analy-
ses: the PRISMA statement. Phys. Ther. 2009;89:
873–880.
25. Vargas-C
aceres S, Cera N, Nobre P, et al. The impact of psy-
chosis on sexual functioning: a systematic review. The j. of
sexual med 2021;18:457–466.
26. National Institutes of Health. (2014). Quality assessment tool
for before-after (pre-post) studies with no control group. Sys-
tematic evidence reviews and clinical practice guidelines.
Washington, DC: National Institutes of Health.
27. Landis JR, Koch GG. The measurement of observer agree-
ment for categorical data. Biometrics 1977;33:159–174.
28. Fox CA, Knaggs GS. Milk-ejection activity (oxytocin) in periph-
eral venous blood in man during lactation and in association
with coitus. J. Endocrinol. 1969;45:145–146.
29. Ogawa S, Kudo S, Kitsunai Y, et al. Increase in oxytocin secre-
tion at ejaculation in male. Clin. Endocrinol. (Oxf)
1980;13:95–97.
30. Carmichael MS, Humbert R, Dixen J, et al. Plasma oxytocin
increases in the human sexual response. The J. of Clin. Endo-
crinology & Metabolism 1987;64:27–31.
31. Carmichael MS, Warburton VL, Dixen J, et al. Relationships
among cardiovascular, muscular, and oxytocin responses dur-
ing human sexual activity. Arch. Sex. Behav. 1994;23:59–79.
32. Murphy MR, Seckl JR, Burton S, et al. Changes in oxytocin and
vasopressin secretion during sexual activity in men. The J. of
Clin. Endocrinology & Metabolism 1987;65:738–741.
33. Blaicher W, Gruber D, Bieglmayer C, et al. The role of oxytocin
in relation to female sexual arousal. Gynecol. Obstet. Invest.
1999;47:125–126.
34. de Jong TR, Menon R, Bludau A, et al. Salivary oxytocin con-
centrations in response to running, sexual self-stimulation,
breastfeeding and the TSST: the Regensburg Oxytocin
Challenge (ROC) study. Psychoneuroendocrinology
2015;62:381–388.
35. Kruger THC, Haake P, Chereath D, et al. Specificity of the neu-
roendocrine response to orgasm during sexual arousal in men.
J. Endocrinol. 2003;177:57.
36. Caruso S, Mauro D, Scalia G, et al. Oxytocin plasma levels in
orgasmic and anorgasmic women. Gynecol. Endocrinol.
2018;34:69–72.
37. Alley J, Diamond LM, Lipschitz DL, et al. Associations
between oxytocin and cortisol reactivity and recovery in
response to psychological stress and sexual arousal. Psycho-
neuroendocrinology 2019;106:47–56.
38. Dickenson JA, Alley J, Diamond LM. Subjective and oxytoci-
nergic responses to mindfulness are associated with subjec-
tive and oxytocinergic responses to sexual arousal. Frontiers
in psychology 2019;10:1101.
39. Baer RA, Smith GT, Lykins E, et al. Construct validity of the
five facet mindfulness questionnaire in meditating and non-
meditating samples. Assessment 2008;15:329–342.
40.
€
Uckert S, Becker AJ, Ness BO, et al. Oxytocin plasma levels in
the levels of and cavernous blood of healthy males during dif-
ferent penile conditions. World J. Urol. 2003;20:323–326.
41. Salonia A, Nappi RE, Pontillo M, et al. Menstrual cycle-related
changes in plasma oxytocin are relevant to normal sexual
function in healthy women. Horm. Behav. 2005;47:164–169.
42. Rosen C, Brown J, Heiman S, et al. The Female Sexual Func-
tion Index (FSFI): a multidimensional self-report instrument
for the assessment of female sexual function. J. Sex Marital
Ther. 2000;26:191–208.
43. Tavares IM, Vardasca R, Cera N, et al. A review of infrared
thermography as applied to human sexual psychophysiology.
Int. J. Psychophysiol. 2018;133:28–40.
44. Dubin NH, Ghodgaonkar RB, King TM. Role of prostaglandin
production in spontaneous and oxytocin-induced uterine con-
tractile activity in in vitro pregnant rat uteri. Endocrinology
1979;105:47–51.
45. Uvn€
as-Moberg K, Ekstr€
om-Bergstr€
om A, Berg M, et al.
Maternal plasma levels of oxytocin during physiological child-
birth−a systematic review with implications for uterine con-
tractions and central actions of oxytocin. BMC pregnancy and
childbirth 2019;19:1–17.
46. Arletti R, Bazzani C, Castelli M, et al. Oxytocin improves
male copulatory performance in rats. Horm. Behav. 1985;
19:14–20.
47. Coolen LM, Allard J, Truitt WA, et al. Central regulation of
ejaculation. Physiol. Behav. 2004;83:203–215.
48. Althof S, Osterloh IH, Muirhead GJ, et al. The oxytocin antag-
onist cligosiban fails to prolong intravaginal ejaculatory latency
in men with lifelong premature ejaculation: Results of a ran-
domized, double-blind, placebo-controlled phase IIb trial
(PEDRIX). The j. of sexual med 2019;16:1188–1198.
49. Striepens N, Kendrick KM, Maier W, et al. Prosocial effects of
oxytocin and clinical evidence for its therapeutic potential.
Front. Neuroendocrinol. 2011;32:426–450.
50. Turner RA, Altemus M, Enos T, et al. Preliminary research
on plasma oxytocin in normal cycling women: investigating
emotion and interpersonal distress. Psychiatry 1999;62:97–
113.
51. Carter SC. Neuroendocrine perspectives on social attachment
and love. Psychoneuroendocrinology; 1998;23:779–818.
52. Hiller J. Gender differences in sexual motivation. J. of Men's
Health and Gender 2005;2:339–345.
53. Uvn€
as-Moberg K. Oxytocin may mediate the benefits of posi-
tive social interaction and emotions. Psychoneuroendocrinol-
ogy 1998;23:819–835.
54. Depue RA, Morrone-Strupinsky JV. A neurobehavioral
model of affiliative bonding: Implications for conceptualizing a
human trait of affiliation. Behav. Brain Sci. 2005;28:
313–349.
55. Guastella AJ, Mitchell PB, Mathews F. Oxytocin enhances the
encoding of positive social memories in humans. Biol. Psychi-
atry 2008;64:256–258.
10 Cera et al
Sex Med 2021;9:100370
56. Everaerd W, Laan E, Both S, et al. Female sexuality. Psycho-
logical perspectives on human sexuality. John Wiley & Sons,
Inc.; 2000. p. 101–146.
57. Marazziti D, Baroni S, Mucci F, et al. Sex-related differences in
plasma oxytocin levels in humans. Clin practice and epide-
miol. in mental health: CP & EMH 2019;15:58–63.
SUPPLEMENTARY MATERIALS
Supplementary material associated with this article can be
found in the online version at doi:10.1016/j.esxm.2021.100370.
Systemic Oxytocin and Sexual Behavior 11
Sex Med 2021;9:100370