Oxytocin is a naturally occurring cyclic Peptide hormone composed of nine amino acids. It mainly acts as a neurotransmitter in the brain and is secreted by the pituitary gland.^[1]  The synthetic form of Oxytocin, called Recombinant Oxytocin, is also a cyclic nonapeptide that is analogous to the naturally occurring peptide. ^[2]

Synthesized by the hypothalamus, the compound is secreted and stored in the posterior pituitary gland and is later released in the body upon hormonal stimulation. ^[3]

Oxytocin peptide works through a positive feedback mechanism. This means that the initial secretion of the hormone peptide leads to further release of the peptide in higher concentrations and with higher intensity. Both synthetic and natural forms of the peptide work through the exact mechanism causing a similar response in the female reproductive system.
 

Benefits of the Oxytocin Peptide

Uterine contractions and Labor induction

Oxytocin is derived from a Greek word where ‘Oxus’ means swift, and ‘tokos’ means childbirth. As indicated by its name, the peptide helps make childbirth faster and smoother.

“Oxytocin is indicated and approved by the FDA for two specific time frames in the obstetric world: antepartum and postpartum. In the antepartum period, exogenous oxytocin is FDA-approved for strengthening uterine contractions with the aim of successful vaginal delivery of the fetus. There are three situations during the antepartum period, which indicate the use of oxytocin. These include mothers with preeclampsia, maternal diabetes, premature rupture of the membranes, mothers with inactive uteri that require stimulation into labor, and mothers with inevitable or incomplete abortions in their second trimester. Postpartum, oxytocin is FDA-approved when it is time to deliver the placenta during the third stage of labor and control postpartum hemorrhage.” ^[3]

Once in the system, the peptide binds with the G-protein coupled receptors found in the uterus membrane, increasing intracellular calcium levels. This calcium secretion then causes uterine contractions. Once the uterine contractions begin, it stimulates the release of the compound, leading to higher frequency and intensity of the contractions via a positive feedback mechanism. 

A clinical study ^[4] was conducted to determine the rate of cesarean delivery in women after discontinuing the compound administration once active labor began (5 cm cervical dilation) compared to women where Oxytocin was administered until the maintenance level as determined in the clinical trial study protocol. The study observes that the percentage of cesarian deliveries was much higher if Oxytocin administration was stopped partway versus those who were given the peptide until birth. This result demonstrates that Oxytocin positively induces labor.
 
Breastfeeding

The peptide causes contraction of the myoepithelial cells found in the alveolar ducts of the female breasts. These contractions stimulate milk ejection from these alveolar ducts into the larger sinuses, thereby expelling milk. The positive feedback mechanism also works here, and initial milk expulsion stimulates further peptide release and continuous milk release. ^[3]

An study was conducted^[5] and found that of the participants who were successfully breastfeeding, 27% were supplemented with doses of Oxytocin, whereas only 14% were not. While further research is needed, the evaluation strongly suggests that Oxytocin positively affects lactation and helps to increase breastfeeding duration.

Here are some additional benefits of the peptide: 

• Oxytocin possesses vasodilatory properties, which can help improve cardiac function and tone in the heart muscles. A study^[6] showed that Oxytocin helped regulate the blood pressure and heart rate in pregnant women upon administration. 
• Oxytocin has been shown to have a positive effect on the social behavior abilities of autistic patients.^[7] Autism is a psychiatric disorder related to poor brain development impacting how people socialize and communicate with others. This discovery shows that this peptide can potentially be used in psychiatric treatment.
• Another neurological ailment in which Oxytocin has shown positive effects is Schizophrenia. Schizophrenia is a chronic neurological disorder characterized by hallucinations, impaired speech, and lack of motivation. Schizophrenia is mainly caused due to an imbalance in Oxytocin levels; therefore, administering supplemental dosages of the peptide may help maintain the brain’s Oxytocin at equilibrate levels.^[8]
• It is also helpful in treating patients suffering from obsessive-compulsive disorder (OCD). However, there were also increased cases of memory disturbances and instances where the patients showed reduced sodium levels in blood plasma and decreased osmolality. Therefore, a clear understanding is yet to be established, and additional studies are to still in process to clearly show if the peptide helps treat OCD patients.

What are the side effects of the Oxytocin peptide?

The common side effects of Oxytocin administration are: ^[3] 

• Irritation and redness at the site of injection
• Nausea
• Vomiting
• Stomach ache
• Appetite loss 
• Increased contractions
• Breathing difficulties 
• Abnormal bleeding

Serious adverse effects of the peptide include:

• Irregular heart rhythm 
• Seizures
• Hallucinations, delusions 
• Elevated blood pressure 
• Blurred vision

Contradictions 

There can be certain contradictions towards Oxytocin primarily due to hypersensitivity towards the peptide or a synthetic version of it. The following conditions can lead to contradictions in administering the peptide: ^[3]

• When the fetal position is abnormal 
• Cervical cancer
• Herpes
• Women with pelvises too small to handle standard delivery 
• Women with a uterus that is highly active and tonic
• High blood pressure^[9]
• Placental previa (a condition where the placenta blocks the uterine neck)^[9]
• Uterus surgery / cervical surgery^[9]

Can improper Oxytocin dosage lead to toxicity?

It is critical to monitor the fluid levels of the patients after Oxytocin administration.^[7] Improper dosing of Oxytocin may cause severe toxic reactions in the patients, such as arrhythmia and ischemia, and high doses can also lead to spasms and even uterine rupture. 

In 2012, a retrospective study ^[6] was conducted where the hemoglobin levels of the women treated with this compound during labor were examined. Women treated with higher Oxytocin doses led to extremely high blood loss compared to women either treated with moderate Oxytocin levels or not treated with the peptide. This demonstrates that improper dosing of the peptide hormone can lead to severe adverse effects. 

United States FDA approval status 

Oxytocin is approved by the FDA to be used in antepartum (to induce uterine contractions and labor) and postpartum (to control post-delivery hemorrhage) stages.^[3]

However, it should be noted that the product is not yet FDA-approved for treating psychiatric disorders in humans.^[10]

Conclusion

Oxytocin is a nonapeptide hormone that primarily exerts its facilitating capabilities on the female reproductive system. Available in both endogenous (natural) and exogenous (synthetic) forms, Oxytocin primarily works via a positive feedback mechanism. 

The primary benefits of the peptide are that it stimulates uterine muscle contraction (used to induce labor) and increases milk ejection (used to induce lactation). Besides, it also possesses vasodilatory effects and may play a vital role in monitoring psychiatric disorders. 

Since its discovery over 100 years ago, Oxytocin has been rigorously studied for labor induction and postpartum use. However, further peptide studies are still underway, especially to explore its role in potentially treating human psychiatric disorders.
 

References: 

1. National Center for Biotechnology Information. “PubChem Compound Summary for CID 439302, Oxytocin” PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Oxytocin 
2. Recombinant Oxytocin (Code C724). https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C724 
3. Osilla EV, Sharma S. Oxytocin. [Updated 2021 Jul 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. https://www.ncbi.nlm.nih.gov/books/NBK507848/ 
4. Induction of Labor with Oxytocin: When Should Oxytocin be held? https://clinicaltrials.gov/ct2/show/results/NCT00957593 
5. Gomes M, Trocadero V, Carlos-Alves M, Arteiro D, Pinheiro P. Intrapartum synthetic oxytocin and breastfeeding: a retrospective cohort study. J Obstet Gynaecol. 2018 Aug;38(6):745-749. Epub 2018 Mar 9. https://pubmed.ncbi.nlm.nih.gov/29523035/ 
6. Rabinow, S., Hjorth, U., Schönbeck, S. et al. Effects of Oxytocin and anesthesia on vascular tone in pregnant women: a randomized, double-blind placebo-controlled study using non-invasive pulse wave analysis. BMC Pregnancy Childbirth 18, 453 (2018). https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186 
7. Cochran, D. M., Fallon, D., Hill, M., & Frazier, J. A. (2013). The role of Oxytocin in psychiatric disorders: a review of biological and therapeutic research findings. Harvard review of psychiatry, 21(5), 219–247. https://doi.org/10.1097/HRP.0b013e3182a75b7d  
8. Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, Hickie IB. Intranasal Oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2010 Apr 1;67(7):692-4. https://pubmed.ncbi.nlm.nih.gov/19897177/
9. Oxytocin Injection. https://medlineplus.gov/druginfo/meds/a682685.html 
10. Cochran, D. M., Fallon, D., Hill, M., & Frazier, J. A. (2013). The role of Oxytocin in psychiatric disorders: a review of biological and therapeutic research findings. Harvard review of psychiatry, 21(5), 219–247. https://doi.org/10.1097/HRP.0b013e3182a75b7d 

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