Most people associate oxytocin with bonding, as this is one of its roles which has been popularised by the media. Medical professionals might associate it with obstetrics, since it is widely used in this department. Although it does indeed affect bonding and can be used in obstetrics, it has effects that extend beyond what the media has told us and how it is currently used in medicine.

In this article, we will examine how oxytocin exerts its effects and what tissues it can influence. This will help us to understand why it is associated with bonding, why it is so useful in obstetrics and why it could potentially have so many other useful therapeutic applications.

 

What is Oxytocin?

Despite the strong association that oxytocin has with being a “love hormone”, it has a broad effect on the body, affecting social behaviour, stress regulation, reproduction and overall health.

Chemically, it is a nonapeptide, meaning it is a small, 9-amino acid-long peptide with the sequence Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly. It is released by the hypothalamus and binds to oxytocin receptors (OXTRs). These receptors are present in the brain and other tissues¹.

Medically, it is best known for its roles in childbirth, where it has been used to stimulate uterine contractions, prevent postpartum haemorrhage and promote lactation for over a century. But broader effects of this hormone have been discovered after its influence on behaviour was discovered in the 1960s. Not only can it act on the brain to affect certain aspects of behaviour, but it can also modulate inflammation and alter metabolism to exert several health benefits. These effects are very much context-dependent and this article will go over some of the factors that can alter them in more detail further on. First, we will take a deeper look into what is known about how oxytocin works and what systems it acts on.

 

Mechanism

Oxytocin exerts its activity through molecular mechanisms and receptor signalling. It binds to OXTRs, which are expressed in the brain and peripheral tissues, the activation of which triggers intracellular cascades that modulate gene expression and neuronal excitability¹.

• Central Actions: In the brain, it acts as a neuromodulator, influencing trust, empathy and bonding. It regulates emotions by reducing neuronal hyperexcitability, leading to anxiolytic and antidepressant effects. It also affects reward processing via dopamine pathways, the ability to pick up on social cues, and learning and memory formation related to social contexts^2–4.
• Peripheral Actions: The peripheral release of oxytocin induces uterine contractions during labour and can stimulate milk ejection during breastfeeding by acting on mammary gland receptors⁵. Since OXTRs are present in many tissues throughout the body, it can also affect cardiovascular function, gut motility and gut barrier integrity, bone metabolism, wound healing and inflammation, appetite, energy expenditure⁶ and pain perception, by activating multiple intracellular pathways⁷.

This wide range of effects demonstrates that oxytocin is far more than a reproductive and bonding hormone, since it can regulate physiological adaptations both centrally and peripherally. Since OXTRs are found in such a wide range of tissues and can trigger a cascade of signalling pathways, what happens if additional oxytocin is administered, or if one becomes deficient in it?

 

Overexpression and Deficiency

From what has been presented so far, it would appear that this hormone is generally beneficial to health, but we cannot assume that simply having more will enhance its effects. This is why it is always interesting to look at models or diseases where there is an excess or a lack of a hormone or its receptor.

 

Overexpression

Oxytocin overexpression has been studied mainly in animal models, where its abundance significantly affects physiology and the pathology of disease. In mice, overexpression of OXTR leads to abnormalities in mammary glands, including:

• hyperplasia
• milk production and
• the development of tumours via the activation of the prolactin/p-STAT5 pathway⁸.

Another mouse model with OXTR overexpression developed symptoms similar to polycystic ovary syndrome, such as:

• hyperandrogenism
• irregular ovulation
• cystic changes and
• metabolic dysfunction⁹.

 

Deficiency

Oxytocin deficiency is a recognised condition, especially in patients with hypothalamic pituitary damage or arginine vasopressin deficiency (central diabetes insipidus). People with these conditions often secrete less of this hormone, which is linked to:

• higher levels of anxiety
• reduced prosocial behaviour
• depression
• impaired sexual function and
• reduced quality of life¹⁰.

We can see some similarities in mouse models with oxytocin deficiency, which exhibit heightened anxiety and an increase in stress hormone release¹¹.

 

What Does This Mean?

These models and case studies emphasise the importance of proper OXTR expression and oxytocin production for normal functioning, as both an excess and a deficiency can lead to the development of health problems.

 

What Happens When Supplemental Oxytocin is Given?

Now that we know what might happen in cases of overexpression, what happens when humans and models are supplemented with oxytocin? Oxytocin is approved for certain medical uses and has been tested on humans for various investigational purposes, so we can see what effects supplementation can have.

 

How is It Delivered?

When given to humans for the purposes of studying social behaviour or neuropsychiatric disorders, it is typically given as an intranasal spray, which allows the hormone to reach the brain easily while also increasing systemic levels. Oromucosal administration is sometimes used instead of intranasal, although the bioavailability is lower. In obstetrics, it is often given intravenously so that levels can be carefully controlled. In animal models, it is usually administered intraperitoneally.

 

Effects of Administration

Some of the main effects in humans include:

• Brain, Behaviour and Mood: An intranasal dose can increase attention to social cues and may improve empathy, trust and cooperation under certain conditions, but the response can vary from person to person¹². A meta-analysis looking at studies on autism spectrum disorder showed a modest improvement in social functioning, although it had little effect on non-social symptoms¹³. In participants with depression or trauma, oxytocin does not always produce a calming effect and sometimes increases anxiety or produces mixed emotional effects^14–16.
• Stress: We know that it modulates the autonomic and immune systems to help the body to cope with stress, inflammation and oxidative damage¹⁷, and supplementing oxytocin may also, to some degree, provide these same benefits, although the results from studies so far are variable.
• Pain: Although animal models would suggest that oxytocin can raise pain tolerance, studies on humans have yielded mixed results, with some showing a reduction in pain sensitivity and others showing no benefit over the placebo¹⁸.
• Metabolism: When given intranasally, it reduces appetite, while increasing fat oxidation and insulin sensitivity in men¹⁹. In people who are overweight, supplementing oxytocin can stimulate weight loss and result in better metabolic profiles²⁰, although not all studies have found it to be effective at reducing weight^21,22.

The effects experienced are strongly affected by sex, history of stress or trauma and context. Given that there are so many variables that can influence the effect that this hormone has on the body, it makes the outcome of supplementing oxytocin difficult to predict.

 

How Effective is it Really?

Its usefulness in obstetrics is undeniable, and it has been used for over a century to facilitate labour and prevent postpartum haemorrhage. When it comes to more recently explored uses, its efficacy is less clear.

It has yielded mixed results in studies on mood, behaviour, stress, pain management and metabolism. We have come to understand that sex hormones can regulate receptor expression and sensitivity, giving them significant influence over the effect that oxytocin has on the body²³.  There are indications that early life experiences may also influence the response of OXTRs, with positive experiences enhancing its activity and promoting healthier social and emotional behaviours. Conversely, negative experiences may reduce the activity of the oxytocin system, possibly leading to a higher risk of anxiety and neuropsychiatric disorders¹⁷. Individual traits or psychiatric conditions²⁴ and the interaction of oxytocin with other systems, such as vasopressin, dopamine and glutamate²⁵ can all influence how OXTR stimulation affects a person. The response of an individual to oxytocin can therefore be prosocial or defensive, depending on the situation and the personal history of that individual.

It is not a drug that will guarantee positive effects on behaviour or social functioning due to the many factors that can influence its activity. This may explain the modest and variable results seen from studies.

 

Safety/Side effects

Most studies are short trials, where oxytocin has been well-tolerated with few serious side effects. In clinical studies, participants tend not to be able to tell whether they received oxytocin or a placebo, suggesting that its effects do not manifest in a way that is physically or mentally noticeable.

Where it has been used for longer periods of time for the management of autism spectrum disorder, people have reported nasal discomfort from the use of the nasal spray, but this and other reported side effects were not statistically more frequent than those experienced by the placebo group²⁶.

In obstetrics, it is associated with benefits such as lower risk of shivering, fever and diarrhoea when compared to those who did not receive oxytocin²⁷. In rare cases, oxytocin administered for labour stimulation has caused antidiuretic effects strong enough to cause water intoxication²⁸.

Generally, both short-term and long-term intranasal oxytocin is well-tolerated and safe when administered under medical supervision²⁹.

 

Conclusion

Oxytocin has a very complex and broad effect on behaviour and physiology. Since it produces such consistent and predictable results in obstetrics, it has been used with confidence in this area of medicine since the 1900’s, but researchers have come to understand its potential use in other areas of medicine. Interestingly, the results that can be seen from many studies on humans, especially those involving behaviour and mood, have been highly variable. Given the popular ideas that have spread via media channels, it is easy to assume that oxytocin would enhance bonding and produce a calming effect, but the research has discovered that this is not always the case. In some, it can increase anxiety, or do very little, while in others it will produce a more predictable, yet modest, outcome.

It seems we have much to learn about oxytocin and the factors that can influence how it affects different people. Further studies on this hormone are needed to gain a better understanding of how it works and how supplementation can be used to more reliably treat diseases.

 

You can buy oxytocin for your research needs here.

 

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