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First-of-Its-Kind Epigenetic Study Links Excessive Oxytocin Levels With Hypersexuality Disorder

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Over the last ten years, much debate has surrounded the classification of compulsive sexual behavior. Should it be regarded as a mental health behavior/disorder?

Hypersexual disorder (HD) was recommended for inclusion in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) by the Sexual and Gender Identity Disorders Workgroup. It was ultimately rejected.

However, the World-Health Organization announced on May 25 2019 that it will include compulsive sexual behavior in the newest addition of the
International Statistical Classification of Diseases and Related Health Problems (ICD-11), scheduled to be implemented in January 2022.

In ICD-11, hypersexual disorder will be defined as:

Compulsive sexual behavior disorder is characterized by a persistent pattern of failure to control intense, repetitive sexual impulses or urges resulting in repetitive sexual behaviour. Symptoms may include repetitive sexual activities becoming a central focus of the person’s life to the point of neglecting health and personal care or other interests, activities and responsibilities; numerous unsuccessful efforts to significantly reduce repetitive sexual behaviour; and continued repetitive sexual behaviour despite adverse consequences or deriving little or no satisfaction from it. The pattern of failure to control intense, sexual impulses or urges and resulting repetitive sexual behaviour is manifested over an extended period of time (e.g., 6 months or more), and causes marked distress or significant impairment in personal, family, social, educational, occupational, or other important areas of functioning. Distress that is entirely related to moral judgments and disapproval about sexual impulses, urges, or behaviours is not sufficient to meet this requirement.

In general, men exhibit hypersexuality more frequently than women. However, robust data outlining the gender differences is sparse.1 Research
 suggests that HD may manifest in adolescence, but its precise neurobiology is unknown.2    

A new study of men and women with HD is published in the journal
Epigenetics, and suggests a role for the hormone oxytocin in its pathophysiology.

"We set out to investigate the epigenetic regulatory mechanisms behind hypersexual disorder so we could determine whether it has any hallmarks that make it distinct from other health issues," says lead author
Adrian Boström from the Department of Neuroscience at Uppsala University, Sweden who conducted the study with researchers from the Andrology/Sexual Medicine Group (ANOVA) at Karolinska Institutet, Stockholm, Sweden.3

Understanding epigenetic regulatory mechanisms

The researchers adopted an
epigenetic approach to study HD. Epigenetics refers to modifications of DNA that do not alter the underlying DNA sequence. These modifications include the addition of chemical compounds to single genes that can regulate their activity – i.e. enhancing or repressing their activity. 

The most common type of epigenetic modification is methylation, in which methyl groups consisting of one carbon atom and three hydrogen atoms are added to DNA segments. The addition of the methyl group effectively "turns off" the gene, and so the encoded protein from that gene is not produced. Epigenetic mechanisms can go awry in cells, and this can manifest as abnormal gene activity or loss of function, resulting in disorders. 

Disrupted epigenetic regulatory mechanisms in HD

In this study, the researchers measured DNA methylation patterns in the blood of 60 patients diagnosed with HD. The measurements were then compared to a control group of 33 healthy volunteers.

The scientists analyzed 8,852 regions of DNA methylation associated to nearby microRNAs to look for any variation between the samples. Where changes in DNA methylation were identified, they looked at the level of gene expression of the associated microRNA.

MicroRNAs are interesting to scientists as they are able to pass the blood-brain-barrier and influence the expression of several thousand genes in the brain and surrounding tissues.

The results showed two regions of DNA that were altered in HD patients, and an associated microRNA, identified as microRNA-4456, was found to be under-expressed.

MicroRNA-4456 targets genes that are typically expressed at high levels in the brain and are implicated in the regulation of the hormone oxytocin. Under-expression of microRNA-4456 would therefore be expected to result in elevated levels of oxytocin. The study doesn’t show a causal relationship here, but it points further research in that direction. 

"To our knowledge, our study is the first to implicate dysregulated epigenetic mechanisms of both DNA methylation and microRNA activity and the involvement of oxytocin in the brain among patients seeking treatment for hypersexuality," say the authors.

The neuropeptide oxytocin is often dubbed the "love hormone", a term that is fiercely debated in the scientific community. Research has demonstrated that oxytocin is linked with the regulation of social and pair-bonding, sexual reproduction and also aggressive behavior in both males and females.

It is also implicated in addictive behaviors. In this study, the scientists decided to compare their findings from the HD group to 24 alcohol-dependent subjects, to explore an association with addictive behavior. They found that the same DNA region was significantly under-methylated, implying that it may be primarily associated with the addictive traits of HD, such as compulsivity and impulsivity. 

A sought-after therapeutic option?

Literature in the clinical space has discussed the use of pharmacological treatment to regulate oxytocin levels in addictive behavioral disorders.3 The authors suggest that this could be a possible avenue for HD, but more study is required: "Further research will be needed to investigate the role of microRNA-4456 and oxytocin in hypersexual disorder, but our results suggest it could be worthwhile to examine the benefits of drugs and psychotherapy to reduce the activity of oxytocin," says Professor Jussi Jokinen from Umeå University, Sweden.

The scientists also acknowledge a limitation to their study in that the mean difference in DNA methylation between HD patients and healthy volunteers was only 2.6%. The impact on physiological changes between the two groups therefore is unclear. Nonetheless, increasing evidence is suggesting that even a subtle methylation change can have wide-ranging consequences, so the study results should not be discounted. 


1.      Kraus et al. 2018. Compulsive sexual behaviour disorder in the ICD‐11. World Psychiatry. DOI: 10.1002/wps.20499.

2.       Reid et al. 2019. Report of findings in a DSM-5 field trial for hypersexual disorder. The Journal of Sexual Medicine. doi: 10.1111/j.1743-6109.

3.      Lee et al. 2016. Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date. CNS Drugs. doi: 10.1007/s40263-016-0313-z.