High Plasma Oxytocin Levels in Men With Hypersexual Disorder
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The Journal of Clinical Endocrinology & Metabolism, 2022, XX, 1–7
https://doi.org/10.1210/clinem/dgac015
Advance access publication 2 February 2022
Clinical Research Article
High Plasma Oxytocin Levels in Men With Hypersexual
Disorder
John Flanagan,1 Andreas Chatzittofis,2,3, Adrian Desai E. Boström,3,4 Jonas Hallberg,1 Katarina
Downloaded from https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgac015/6516736 by guest on 08 March 2022
Görts Öberg,1 Stefan Arver,1 and Jussi Jokinen3,5
1
Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
2
Medical School, University of Cyprus, Nicosia, Cyprus
3
Department of Clinical Sciences/Psychiatry, Umeå University, Umeå, Sweden
4
Neuropaediatric Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
5
Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden
Correspondence: Andreas Chatzittofis, MD, PhD, University of Cyprus, Medical School, Palaios dromos Lefkosias Lemesou No.215/6 2029 Aglantzia, Nicosia,
Cyprus. Email: chatzittofis.andreas@ucy.ac.cy.
Abstract
Context: Hypersexual disorder (HD) involves excessive, persistent sexual behaviors related to various mood states and the diagnosis com-
pulsive sexual behavior disorder is included as an impulse control disorder in the 11th revision of the International Classification of Diseases.
Although the neurobiology behind the disorder is not clear, some studies suggest dysregulated hypothalamic-pituitary-adrenal axis. Oxytocin
acts as counterregulatory neuroendocrine hormone to cortisol and is also involved in sexual behavior.
Objective: We hypothesized that oxytocin may play a role in the pathophysiology of HD with compensatory actions to cortisol.
Design: Longitudinal.
Setting: ANOVA clinic (Karolinska University Hospital).
Patients or other participants: 64 males with HD and 38 age-matched healthy volunteers.
Main Outcome Measures: Plasma oxytocin levels, measured with radioimmunoassay; Hypersexual Disorder Screening Inventory; and
Hypersexual Disorder: Current Assessment Scale for assessing hypersexual symptoms.
Interventions: A patient subgroup (n = 30) completed the manual-based group-administered cognitive-behavioral therapy (CBT) program for
HD, and posttreatment oxytocin levels were measured.
Results: Hypersexual men (n = 64) exhibited significantly higher oxytocin plasma levels (mean ± SD: 31.0 ± 9.9 pM) compared with healthy
volunteers (16.9 ± 3.9 pM; P < 0.001). There were significant positive correlations between oxytocin levels and the rating scales measuring
hypersexual behavior. Patients who completed CBT treatment (n = 30) had a significant reduction of oxytocin plasma levels from pretreatment
(30.5 ± 10.1 pM) to posttreatment (20.2 ± 8.0 pM; P < 0.001).
Conclusions: The results suggest that the hyperactive oxytocinergic system in hypersexual men may be a compensatory mechanism to at-
tenuate hyperactive stress.
Key Words: oxytocin, hypersexual disorder, compulsive sexual behavior disorder, cognitive behavioral therapy
Introduction regulation, the limbic system, and inhibitory frontal lobe ac-
Hypersexual disorder (HD) is considered a nonparaphilic tivity (4,5). Although sexual response studies have implicated
sexual desire disorder that involves excessive and persistent dopamine, serotonin, neuropeptides, glutamate, and gamma
sexual behaviors in relation to various mood states, with an aminobutyric acid (6,7), little is known how they influence
impulsivity component and experienced loss of control (1). patients with excessive sexual behavior/HD.
HD was originally suggested as a diagnostic entity for the fifth Insights into the pathophysiology of HD have been de-
edition of the Diagnostic and Statistical Manual of Mental scribed recently, such as endocrine dysregulation and differ-
Disorders (2), and a similar disorder is now included in the ences in the brain’s functional systems (8). Chatzittofis et al
11th revision of the International Classification of Diseases demonstrated that men diagnosed with HD showed evidence
(ie, compulsive sexual behavior disorder, which is classified of neuroendocrine dysregulation, using the dexametha-
as an impulse control disorder) (3). Although the inclusion sone suppression test as a proxy variable for a dysregulated
of compulsive sexual behavior disorder was a significant hypothalamic-pituitary-adrenal (HPA) axis, compared to
step forward for the identification and treatment of suffering healthy subjects (9).The hypothalamic-pituitary-gonadal axis
individuals, there is still a lack of knowledge regarding the was also reported to be dysregulated in HD. Men with HD
pathophysiology underlying the disorder. Sexual behavior is had higher luteinizing hormone plasma levels, but testos-
a complex process and under the control of neuroendocrine terone levels did not differ compared to healthy controls (10).
Received: 3 September 2021. Editorial Decision: 9 January 2022. Corrected and Typeset: 2 February 2022
© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://
creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the
original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@
oup.com2 The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX
In addition, epigenetic changes in the CRH gene, an essen- conditions, or substance abuse). Participants using dopamine
tial gene involved in the cortisol stress responses in the brain, agonists were also excluded. The participants applied for the
were reported in men with HD (11). Another important study by submitting informed consent and valid contact in-
neuroendocrine system that might be implicated in the patho- formation on a secure Internet platform. They were then in-
physiology of HD is oxytocin. Oxytocin is involved in social structed to complete an online screening battery consisting of
bonding, sexual behavior stress regulation, and the reward 23 structured questionnaires on sociodemographics, overall
pathway (6,12,13). Existing findings suggest that central oxy- psychiatric status, and hypersexual behavior/symptoms.
tocin release contributes to the modulation and maintenance Following the initial online screening, eligible participants
of cortisol levels that favor a rapid return to prestress baseline were assessed in clinical interviews with a psychiatrist and
states as well as having a neuromodulatory role on the reward a clinical psychologist, both experienced within the field of
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pathway with inhibitory effects on addictive behaviors (14). sexual medicine. The interviews aimed to establish the par-
Moreover, a recent epigenetics study implicated the involve- ticipants’ HD diagnostic status in accordance with the pro-
ment of microRNA-4456, believed to regulate genes involved posed HD criteria (1) and to assess their overall psychiatric
in the oxytocin signaling pathway, in HD (15). However, comorbidity using the Mini International Neuropsychiatric
other than this epigenetic study, no study to date has evalu- Interview 6.0 (16). In total, 64 (n = 64) HD-diagnosed par-
ated oxytocin levels in HD and their possible relationship ticipants were included in the present study. A subgroup
with hypersexual symptoms. (n = 30) of the included patients were randomized to take
Based on previous research reporting a hyperactive HPA part of a manual-based CBGT program for HD. The re-
axis and the preliminary epigenetic data implicating the maining patients (n = 34) were randomized and assigned to
oxytocinergic system in the pathophysiology of HD, we hy- a waitlist condition.
pothesized an involvement of the oxytocinergic system as a
counterregulator of the cortisol stress system in HD. Controls
In this study, we aimed to examine plasma oxytocin levels For the control group, healthy volunteers were recruited from
in men diagnosed with HD and age-matched healthy con- the Karolinska Trial Alliance database. Exclusion criteria
trols. Further, we aimed to examine the correlations between for the healthy controls were (1) previous or current psychi-
plasma oxytocin levels and dimensional symptoms of HD atric illness; (2) severe physical illness; (3) first-degree rela-
using hypersexual behavior rating scales and whether cogni- tive diagnosed with bipolar disorder, completed suicide, or
tive behavioral therapy (CBT) treatment for HD symptoms schizophrenia; (4) previous exposure to serious trauma; and
influences plasma oxytocin levels. (5) positive screening pedophilia or pedophilic disorder. The
volunteers were prescreened via telephone interviews and, if
found eligible, instructed by the study coordinators to log into
Materials and Methods the Internet platform and submit valid personal information,
The authors assert that all procedures contributing to this their preliminary informed consent to participate in the study
work comply with the ethical standards of the relevant na- and responses to the previously presented online screening
tional and institutional committees on human experimenta- battery. The controls were matched to the included patients
tion and with the Helsinki Declaration of 1975, as revised in regarding age and equivalent blood sample collection times in
2008. The study protocols and informed consent documents the fall or spring to control for possibly interfering seasonal
were approved by the Regional Ethical Review Board in variations. In total, 38 healthy male volunteers were included
Stockholm (registration IDs: 2010/5:3 and 2013/1335-31/2). in the study. Before the baseline blood samples were taken,
Written informed consent was obtained from all participants the controls submitted informed consent for participation in
at the initial screening. the study. For a thorough description of the study population
and study design, see Chatzittofis et al (9).
Setting
This is a single-center, longitudinal study between 2013 and Assessments
2014. The study took place at the ANOVA clinic at Karolinska All participants were assessed by diagnostic clinical interview
University Hospital, which is a multidisciplinary center for re- using the Mini International Neuropsychiatric Interview 6.0
search, assessment, and treatment in the fields of andrology, (16) and self-rating scales by an Internet-based platform using
sexual, and transgender medicine. the following self-rating measures.
Participants Self-rating measures
Patients The Hypersexual Disorder Screening Inventory (HDSI) (17)
Patients (n = 64) were a subgroup of help-seeking men diag- is a tool for screening of a possible HD diagnosis (17). The
nosed with HD, included in a randomized clinical study of inventory consists of 7 items following the A (n = 2) and B
a manual-based, group-administered CBT (CBGT) treat- (n = 5) criteria for HD during the past 6 months. The items
ment program for HD. The inclusion criteria were (1) are rated along 5 graded Likert scales (0-4 points), ranging
age > 18 years; (2) clinically endorsed HD diagnosis; (3) from “never true” to “almost always true,” The total sum
stable in medication regimen of psychoactive compounds score ranges from 0 to 28. For a possible HD diagnosis, a
(≥3 months); and (4) informed consent to participate in the minimum score of 3 is required on 4 out of 5 A criteria, and
study. The exclusion criteria were (1) paraphilias of pedo- a minimum score of 3 or 4 points on at least 1 for the 2 B
philia, voyeurism, exhibitionism, frotteurism, sadism, and criteria items. The inventory has a high internal consistency
sexual coercion and (2) severe psychiatric comorbidity (ie, (α = 0.88-0.96) and high test-retest reliability (r = 0.81) over
severe anxiety, depression, other contraindicating psychiatric a 2-week period. HDSI was used for baseline measurement ofThe Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX 3
HD symptoms and for assessment of the likelihood of posi- Systat Software Inc, London, UK). Skewness and kurtosis of
tive HD diagnosis over the last 6 months. the distribution of continuous variables were evaluated by the
Hypersexual Disorder: Current Assessment Scale (HD:CAS) Shapiro-Wilk test. Oxytocin levels were normally distributed
(18) was used to assesses the HD symptom severity over the both in patients with HD and healthy volunteers. Unpaired
recent 2-week period. HD:CAS consists 7 items. The first (A1) Student t-test was used to investigate group differences in
examines the type as well as the number of sexual behav- oxytocin plasma levels between patients with HD and healthy
iors specifiers (masturbation, pornography consumption, sex volunteers. Correlation analyses were performed using
behaviors with consenting adults, cybersex, telephone sex, Spearman’s rho to determine associations between the clin-
visits to venues for sexual entertainment, and other sexual ical and biologic variables. Paired t-test was used to compare
behaviors). Items 2 to 7 quantify the symptoms during the re- mean plasma oxytocin levels in HD male patients (n = 30) be-
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cent 2-week period. Items 2 to 7 are rated on a 5-point Likert fore and after CBT intervention. Correlational analysis using
scale (0-4 points) rendering a total score range of 0 through Pearson’s r was performed between changes in clinical ratings
24 points. HD:CAS was used as a dimensional measurement (HD:CAS) and plasma oxytocin levels before and after CBT.
of hypersexual behavior. HD:CAS is not validated but has All statistical tests were 2-tailed. The P-value for significance
been used to measure the severity of HD symptomatology in was < 0.05.
studies on HD (9,19-22).
The Childhood Trauma Questionnaire (CTQ) is a Role of the Funding Source
self-assessment tool for examination of childhood trauma. The funding source had no involvement in study design, col-
The questionnaire consists of 28 items. Twenty-five of the lection, analysis, interpretation of data, writing, or the deci-
items are divided into 5 subscales measuring emotional abuse, sion to submit the paper for publication.
physical abuse, sexual abuse, emotional neglect and physical
neglect. The 3 remaining items constitute a minimization/de-
nial scale that pertains to identify individuals who may be Results
underreporting traumatic childhood events (23). CTQ has Oxytocin Levels in HD-diagnosed Men and Healthy
exhibited good test-retest reliability (r = 0.80) and a high in- Controls
ternal consistency for the 4 subscales sexual abuse (α = 0.93- The mean plasma oxytocin level in healthy controls was
0.95), emotional neglect (α = 0.88-92), emotional abuse (mean ± SD) 16.9 ± 3.9 pM (median 16.0, range 8-27,
(α = 0.84-0.89), and physical abuse (α = 0.81-0.86). n = 38), whereas plasma oxytocin levels in the HD-diagnosed
patients were significantly higher at 31.0 ± 9.0 pM (median
CBT intervention 28.0, range, 17-55, n = 64; P < 0.001) (Fig. 1).
The CBGT program consisted of 7 CBT-based modules, pre-
sented in group sessions through lectures and written mater- Correlations Between Oxytocin, HD Symptom
ials over a period of 7 weeks. For a thorough description of Severity, and Adverse Childhood Events
the CBGT program, see Hallberg et al (21). Hallberg et al Next, correlation analyses (Spearman’s rho) were performed
reported significantly greater decrease of HD symptoms for to examine the relationship between plasma oxytocin levels
the treatment group when compared to the waitlist condition and HD symptoms. Both the HDSI scores and HD:CAS scores
(19). showed significant positive correlations with baseline plasma
oxytocin levels (rho = 0.649, P = 0.0000002; rho = 0.661,
Blood Sample Collection and Analysis P = 0.0000002) in the study participants combined (Fig. 2).
Morning blood samples were collected from all study par- The correlations between plasma oxytocin levels and CTQ
ticipants between 2013 and 2014 (n = 102), according to scores were nonsignificant.
standard procedures. After preparation of serum and plasma,
samples were stored at −80°C until assayed. All participants Effect of CBT Intervention on Plasma Oxytocin
were fasting at the time for the blood sample collection. For Levels in Patients With HD
the subgroup of HD-diagnosed patients who underwent the Patients diagnosed with HD were offered to participate in
CBGT program, blood samples were also collected following a 7-week CBT intervention with the goal of reducing their
their final CBT session (approximately 2 months after the hypersexual behavior symptoms. The CBT treatment had re-
baseline blood samples). Routine blood analysis was per- ducing effects on the symptoms in the patients (19). As demon-
formed by the Clinical Chemistry Laboratory at the Karolinska strated in Figure 3, a paired t-test revealed that patients with
University Hospital using standard procedures. The oxytocin HD who completed CBT treatment exhibited a significant
level in blood plasma was determined by radioimmunoassay reduction of oxytocin levels from pretreatment (30.5 ± 10.1
(Antibody: RRID:AB_2894933; https://antibodyregistry.org/ pM) to posttreatment (20.2 ± 8.0 pM; P = 0.0000019).
search.php?q=AB_2894933) at the Clinical Neurochemistry Patients with HD had a significantly positive correlation of
Laboratory, Sahlgrenska University Hospital, Mölndal, their changes in HD:CAS with plasma oxytocin levels before
Sweden. Further assay details were published previously (20). and after CBT (r = 0.388, P = 0.0344).
The assay’s lower limit of detection was 5 pM. The intra- and
interassay coefficients of variation were 14% and 8%, 10% and
15%, and 12% and 10% at 12, 31, and 60 pM, respectively. Discussion
In this study, we discovered that male patients with HD had
Statistical Analysis significantly higher oxytocin levels compared with healthy
All statistical analyses were performed using SigmaSTAT stat- volunteers. Furthermore, the oxytocin levels were signifi-
istical analysis tool within Sigmaplot Software (version 13, cantly positively correlated with the sum scores of rating4 The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX
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Figure 3. Mean plasma oxytocin levels in hypersexual disorder
male patients(n = 30) before and after cognitive behavioral therapy
Figure 1. Boxplot of mean plasma oxytocin levels in hypersexual intervention. P-value was calculated by paired t-test.
disorder male patients(n = 64) and healthy male controls (n = 38). P-value
was calculated by t-test. (line = median, box = Q1-Q3 interquartile range,
bars = minimum and maximum).
involvement in HD and the discovery of oxytocin as a po-
tential biomarker for diagnosis and potential drug target for
treatment.
It is important to interpret the results bearing in mind
the effects of oxytocin on sexual behavior, stress regulation,
and psychopathology. Oxytocin, besides associated with
childbirth and lactation, may exert additional regulatory
functions in male sexuality. For example, oxytocin is a key in-
ducer of penile erection in animal studies (24) with oxytocin
neurons projecting from the paraventricular nucleus (PVN) to
extrahypothalamic regions in the brain and spinal cord (25).
In support, oxytocin was implicated in ejaculation (26-28),
with a significant activation of PVN oxytocin neurons after
stimulus of the dorsal penile nerve, leading to the hypothal-
amic release of oxytocin at ejaculation (29). This increase in
oxytocin may exert an effect on sexual behavior (30), with
plasma oxytocin levels being associated with orgasm intensity
in both sexes (31) and naloxone-induced oxytocin suppres-
sion has been shown to decrease sexual satiety (32), while not
inhibiting ejaculation. Moreover, in animal studies, cerebro-
spinal fluid (CSF) oxytocin levels are greatly increased shortly
after ejaculation (33). This effect is completely subdued by the
induced damage to the parvocellular neurosecretory neurons
of the PVN (33), underlying the key role of this brain region
in facilitating oxytocin activity. Intriguingly, oxytocin is im-
portant in pair bonding and monogamous behavior in animal
studies, and variation of oxytocin receptor gene may also be
of importance in pair bonding in women and men (34,35).
Apart from its purported role in sexuality, the oxytocinergic
system is implicated in regulating complex social behav-
Figure 2. Scatterplots of plasma oxytocin levels and self-rating scales iors acting in concert with other neurotransmitters (35-39).
measuring hypersexual behavior in hypersexual disorder male patients Interactions with serotonin may influence social reward
(represented by solid black triangles) and healthy male controls processing in the nucleus accumbens and dopamine inter-
(represented by solid black circles). (A) Hypersexual Disorder Screening
actions regulate social behaviors (38,39). In addition, by
Inventory (HDSI) and (B) Hypersexual Disorder: Current Assessment
Scale (HD:CAS). Spearman correlation rho values are indicated in each
modulating HPA axis activity and amygdala responsiveness
graph and all correlations had P-values =The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX 5
oxytocin could be an indirect consequence of oxytocin acting role of oxytocin in HD compared to a case-control study set
to reduce the responsiveness of the HPA axis (42). Animal up by also analyzing the effects of CBT intervention. Third,
studies further suggest the oxytocin and HPA axis systems previous studies that have implicated effects of exogenous
may share partly intertwined trajectories, exhibiting both co- oxytocin administration may vary by sex in specific cases. As
ordinated and autonomous activity, the details of which are such, the present study pertained only to male subjects to ex-
not yet known comprehensively (47). In support of contextual clude sex as a potential source of bias in the association ana-
independent action, Thomas and Larkin demonstrated that lysis between HD and oxytocin levels.
rumination in human subjects was associated with elevated Limitations of the present study include the lack of oxy-
cortisol and reduced oxytocin levels (48). tocin levels measurements from a waitlist or control group
The role of oxytocin has been investigated in other as well as the use of radioimmunoassay instead of the gold-
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psychopathologies that exhibit severe impulsivity standard stable isotope dilution mass spectrometry. There are
dysregulation similar to HD, such as borderline person- many potential confounding factors on the association ana-
ality disorder (BPD) and addiction. While reduced oxytocin lysis between HD and plasma oxytocin levels before and after
plasma levels have been reported in BPD compared to healthy CBT intervention. The study group was made as reasonably
controls (49-51), the exogenous administration of oxytocin homogenous as possible, and individuals were excluded if
in subjects with BPD reported partly inconsistent results (52). they exhibited addictive or psychotic illnesses and other severe
A majority of studies reported on improved social skills after physical illness. However, other possible confounding factors
oxytocin administration and generally different effects in pa- cannot be excluded completely, (eg, dietary patterns, ethni-
tients and controls. The authors speculated that childhood city). For example, a systematic review noted a significant
trauma, which is commonly present in subjects with BPD, effect on oxytocin plasma levels of diet and dietary behav-
may cause an adverse reaction to oxytocin with increased iors in clinical samples but not in nonclinical samples, which
antisocial behavior. Moreover, the oxytocinergic system has suggests that even meal consumption patterns were a poten-
been widely implicated in addiction pathophysiology, pur- tial factor unaccounted for bias (63). Moreover, while consid-
portedly acting to abate drug-seeking behavior, craving, and erable effort was put into ensuring the blood measurements
relapse from some of the most commonly abused substances, were as standardized and homogenous as possible, effects of
including cocaine, marijuana, and alcohol (53-55). timing from physical exercise prior to sampling, perceived
Another defining feature of HD is compulsivity. In this re- stress, social interactions, and intra-individual variability, as
gard, obsessive-compulsive disorder (OCD) may share some well as sample storage, cannot be excluded (64). However,
common etiology with HD. Studies investigating oxytocin controlling the time of sample collection and processing sam-
levels in OCD have been mostly inconclusive, and the litera- ples immediately, with storage at −80°C minimizes possible
ture on the therapeutic effect of exogenous oxytocin adminis- effects (65). Especially, the present study did not consider
tration has not reported consistent results (56). Of interest, a potential sexual activity prior to oxytocin measurements. As
study demonstrated that the debut age of OCD was inversely ejaculation is known to significantly increase plasma oxytocin
associated with oxytocin levels (57). In support of this hy- levels in the short term after ejaculation, future studies should
pothesis, gene polymorphisms of the oxytocin receptor gene address and properly account for this potential source of bias.
(OXTR) were associated with late-onset OCD (58). However, it was reported that plasma oxytocin levels fell to
Thus, our results of high oxytocin levels, together with pre- basal concentrations 30 minutes after ejaculation (27). This
viously reported noninhibition and hyperactivity of the HPA relatively short time frame, combined with the procedures
axis, are in line with previous research reporting compensa- for blood sampling, suggest this as a less probable source of
tory effects of oxytocin to the HPA function. This function of confounding factors. Moreover, as oxytocin levels were meas-
oxytocin has been proposed both from addiction research as ured in plasma, it can be disputed whether the observed al-
well as stress research. terations reflect pathophysiological alterations in CSF, where
Most human therapeutic studies targeting oxytocin utilize the key biological effects of oxytocin are believed to occur.
intranasal administration of oxytocin (52). While oxytocin Although there is no clear consensus at this point (66), pre-
receptor antagonists have traditionally been researched vious studies support the use of oxytocin plasma levels as a
in the context of childbirth (59), emerging animal studies surrogate variable for CSF oxytocin activity (67). However,
investigating the effects of oxytocin receptor antagonism replicating our findings in CSF oxytocin would be valuable.
report effects on social behavior and, to a lesser extent, on Finally, replicating our findings in independent study groups
HPA responses (60) whereas the administration of oxytocin using larger sample sizes would be useful in confirming the
receptor antagonism to male rats, resulted in reduced sexual presented results.
drive (61). In summary, this is the first study to investigate oxytocin
In addition, to the best of our knowledge, no studies have in HD using a longitudinal study approach. We present our
hitherto investigated the effects of CBT on plasma oxytocin novel findings in demonstrating elevated plasma oxytocin
levels. A recent study indicated that baseline plasma levels levels in cases of HD compared to controls. Moreover, we
of oxytocin predict psychotherapeutic treatment outcome in provide evidence that these excessive oxytocin levels are ef-
chronic depression (62). However, the study did not measure fectively normalized after CBT treatment. As such, oxytocin
oxytocin levels postintervention. The present study has sev- holds promise as a potential biomarker for HD diagnostics
eral strengths. First, a representative and well-characterized and as a measure of disease severity. Taken together, these
patient population of subjects with HD and controls contrib- findings motivate further research to elucidate the explicit role
uted to minimizing cohort bias. Second, the longitudinal and of oxytocin in HD pathophysiology. Importantly, additional
interventional study set up considered the dynamic quality studies excluding potential confounding factors from recent
of oxytocin. Thus, our study more specifically elucidated the sexual activity are needed before causality can be inferred.6 The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX
Funding 15. Boström AE, Chatzittofis A, Ciuculete DM, et al. Hypermethylation-
associated downregulation of microRNA-4456 in hypersexual
Funding for this study was provided through a regional agree- disorder with putative influence on oxytocin signalling: a
ment between Umeå University and Västerbotten County DNA methylation analysis of miRNA genes. Epigenetics
Council (ALF) and by grants provided by the Stockholm 2020;15(1-2):145-160.
County Council (ALF) (Jussi Jokinen); and by Swedish 16. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The mini-international
Research Council Grant number (Jussi Jokinen, 2020-01183). neuropsychiatric interview (M.I.N.I.): the development and valida-
tion of a structured diagnostic psychiatric interview for DSM-IV
and ICD-10. J Clin Psychiatry. 1998;59(Suppl 20):22-33;quiz 34.
Author Contributions 17. American Psychiatric Association’s DSM-5 Workgroup on Sexual
and Gender Identity Disorders Hypersexual Disorder Screening
J.F, A.C., S.A., and J.J. conceptualized the study. All the au-
Downloaded from https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgac015/6516736 by guest on 08 March 2022
Inventory. American Psychiatric Association; 2010.
thors were responsible for the design of the study. A.C., J.H., 18. American Psychiatric Association’s DSM-5 Workgroup on Sexual
K.G.Ö., and J.F. were responsible for the data collection. and Gender Identity Disorders. Hypersexual Disorder: Current
A.E.B., J.F., and J.J carried out the statistical analyses and Assessment Scale. American Psychiatric Association; 2010.
verified the underlying data. All the authors were responsible 19. Hallberg J, Kaldo V, Arver S, Dhejne C, Jokinen J, Öberg KG. A
for the interpretation of the data. J.F. wrote the first draft randomized controlled study of group-administered cognitive
of the manuscript. All authors revised the paper critically for behavioral therapy for hypersexual disorder in men. J Sex Med.
important intellectual content and gave final approval of the 2019;16(5):733-745.
version to be published. 20. Nielsen EI, Al-Saqi SH, Jonasson AF, Uvnäs-Moberg K.
Population pharmacokinetic analysis of vaginally and intrave-
nously administered oxytocin in postmenopausal women. J Clin
Disclosures Pharmacol. 2017;57(12):1573-1581.
21. Hallberg J. Hypersexual Disorder: Clinical Presentation and
The authors have nothing to disclose. Treatment. Department of Medicine. Vol Doctoral. Karolinska
Institutet; 2019.
Data Availability 22. Nair D, Pawar A, Kalra G, Shah N. An Indian study of hypersexual
disorder in patients with anxiety and mood disorders. Sex Addict
Some or all data sets generated during and/or analyzed during Compulsivity. 2013;20(4):292-305.
the current study are not publicly available but are available 23. Bernstein DP, Stein JA, Newcomb MD, et al. Development and val-
from the corresponding author on reasonable request. idation of a brief screening version of the childhood trauma ques-
tionnaire. Child Abuse Negl. 2003;27(2):169-190.
24. Argiolas A. Oxytocin stimulation of penile erection: phar-
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