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Oxytocin is a peptide hormone made of nine amino acids and is secreted by the posterior pituitary gland in the brain.  Oxytocin was first discovered in 1906 by Sir Henry Dale, and its name was derived from the Greek, meaning “Swift Birth.”[i]

Oxytocin plays a well-known role in pregnancy-related uterine contractions and lactation.  Recent research has brought to light a new understanding of oxytocin actions in many other body systems.  Oxytocin has been shown to modulate the stress response.  It contributes to pain perception in chronic pain syndromes.  Oxytocin facilitates human sociability, including trust, attachment and intimacy.  In the sexual sphere, oxytocin is involved in both male and female orgasm.  Finally, it may influence mood and ameliorate feelings of depression.

The following are a collection of areas where oxytocin researchers have concentrated their attention.

Stress Management, Anxiety and Depression

Oxytocin exerts anxiolytic and stress attenuating effects.  The mechanism of action appears to be an inhibitory influence on stress-induced activation of the hypothalamic-pituitary axis (HPA) axis.  Early oxytocin research found that lactating women had reduced plasma ACTH, cortisol and glucose responses in comparison to postpartum non-lactating women.  A later study demonstrated that supplemental oxytocin in the form of a nasal spray decreased the stress response to a psychological stressor.  This study, a double blind placebo controlled trial, subjected men to a stressful public speaking event in a controlled setting.  Supplemental oxytocin together with social support before the stressful event significantly reduced cortisol and increased calmness.[ii]  Oxytocin replacement appears to have interesting potential as a therapeutic stress response attenuator.

Oxytocin’s role in ameliorating depression is somewhat more complex.  Several animal studies suggest that oxytocin improves mood.[iii]  However, a recent paper revealed that endogenous oxytocin secretion after meals was actually higher in people with anorexia.  Endogenous oxytocin secretion was also higher if these individuals with anorexia also had depression.[iv]  It appears that anorexia may be a condition in which oxytocin supplementation is contraindicated.

Cardiac tissue is one of the lesser known locations for oxytocin action.  In a rat study, endogenous oxytocin acted to moderate the cardiovascular response to stress.  Further, rats treated with oxytocin experienced reductions in blood pressure although the effect was not observed in female rats.[v]

Autism

Autism is an area of intense oxytocin research.  The US Center for Disease Control reports a 78% increase in Autism Spectrum Disorder prevalence between 2002 and 2008, with an overall worldwide incidence of approximate 1%.  Studies have demonstrated that children and adults with autism have decreased oxytocin levels compared to controls.  Emerging research shows that supplemental oxytocin in children with autism improves emotional recognition and the ability to assign significance to emotional speech.  In other studies, oxytocin also enhanced feelings of trust, promoted gazing time into the eyes and decreased other autism related symptoms.  Further large scale trials are needed to assess the full potential of oxytocin treatment in this population.  Also, pediatric reference ranges are not widely available.  There seems however reason to be cautiously optimistic about the future of oxytocin and autism.

Chronic Pain Syndromes

Jorge Flechas, MD deserves credit for pioneering the clinical use of oxytocin in the treatment of Chronic Fatigue Syndrome and Fibromyalgia.  In the book Passion, Sex and Long Life, Dr. Thierry Hertoghe details many remarkable clinical outcomes from Dr. Flechas’ practice.[vi]

Oxytocin plays an intriguing role in pain perception and pain physiology.  Oxytocin receptors participate in modulating visceral pain, which perhaps is not a surprise given oxytocin’s involvement in childbirth.  Researchers studied oxytocin administration in patients with chronic constipation, and while the participants’ bowel habits did not improve more than placebo, there was a trend toward less abdominal pain.  In study participants that also had depression, there was a trend toward an improvement in mood with oxytocin.[vii]  Another study found that oxytocin administered via IV reduced visceral perception in patients with irritable bowel syndrome (IBS).[viii]  Oxytocin receptor stimulation via novel pharmacologic analogues for the treatment of chronic abdominal pain is currently an active area of research[ix],   although some observe that oxytocin itself will stimulate oxytocin receptors, and that non-isomolecular analogues will likely have more adverse effects than oxytocin itself.

Another potential application for oxytocin is in the treatment of acute migraine.  Published reports detail the use of IV oxytocin in both adult and pediatric cases.[x]  As of this writing, a phase II trial is evaluating a nasal oxytocin spray for migraine treatment.[xi]

Sexual Dysfunction

Male erectile tissues are one of the main peripheral target areas for oxytocin.  Oxytocin joins nitric oxide, dopamine, vasopressin and other signaling molecules such as cyclic guanosine monophosphate (cGMP) to regulate erectile function.[xii]  Oxytocin is an emerging agent in the treatment of erectile dysfunction and male anorgasmia, with recent successful case reports published for both conditions.[xiii]^,[xiv]

In women, oxytocin levels are higher after orgasm compared to baseline levels.[xv]  However, oxytocin appears to play a more complex role in the sexual experience in women compared to men.  Oxytocin strengthens attachment, affection and trust between partners, fostering increased intimacy and emotional connection.

Mitigating Factors for Oxytocin Efficacy

Experimental evidence suggests that oxytocin supplementation may have differential effects based upon a person’s background.  People with a history of negative caregiving experiences in their childhood responded differently to oxytocin than people who did not have these negative experiences.  Examples of a “negative caregiving experience” include parental divorce, harsh parental discipline with the use of physical force, or the lack of maternal love in childhood.  Surprisingly, participants with these history elements did not respond as strongly to the oxytocin administration.  For instance, one study examined empathetic behavior and oxytocin administration, as influenced by a background of “parental love withdrawal” as a disciplinary measure.   (Oxytocin has been shown to enhance a person’s empathy toward those who are disadvantaged.)  In this study, oxytocin significantly enhanced the adult participants’ willingness to donate money to a charitable cause, but only if their childhood was free of excessively harsh disciplinary measures.[xvi]  The study used the Parental Discipline Questionnaire (PDQ) outlined by Patrick and Gibbs in 2007.  The implications of this research suggest reduced trust and sociability gains for patients taking oxytocin if they have a history of poor parental attachment.  It is unclear whether the benefits in chronic pain management or stress are similarly attenuated.

Clinical Considerations for Oxytocin

Oxytocin holds potential to improve the quality of life for many patients across a number of different conditions.  Consider testing oxytocin levels in the following clinical scenarios:

• Autism
• Depression
• Sexual dysfunction, especially erectile dysfunction
• Chronic pain syndromes
• Maladaptive stress syndromes
• Cases of extreme social avoidance/ social withdrawal

Oxytocin’s side effect profile appears relatively benign, with two recent studies reporting on adverse effects in children and adolescents.  Neither study found severe side effects of any kind, metabolic or otherwise.  The first study tracked 8 male participants for six months.[xvii]  The second study used an intranasal dose of up to 0.4IU/kg/dose given twice a day.[xviii]

Orally administered oxytocin, due to its peptide structure, is rapidly degraded by peptidases in the gut.  Plasma-delivered oxytocin, such as an IV injection, does not appear to cross the blood brain barrier.  Intranasal oxytocin is currently the favored administration method because of its absorption through the nasal mucosa.  Vasopressin, a structurally similar neuropeptide, was shown to cross the blood brain barrier and access the cerebrospinal fluid within 30min.[xix]

24-hour oxytocin urine testing holds several key advantages.  A 24-hour test is a non-invasive means of assessment and additionally captures a full day’s secretion.  This 24-hour perspective is critical because oxytocin secretion can be highly situational, triggered by social and sexual activities.  A 24-hour perspective therefore affords a more comprehensive oxytocin assessment compared to other methods that only measure an isolated snapshot in time.

In conclusion, oxytocin is well-suited as an adjunct to any regimen that seeks to restore hormonal balance, whether in concert with Bio-Identical Hormonal Replacement (BHRT) or other natural medicines.

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References

[i] Viero C et al. Review: Oxytocin: Crossing the bridge between basic science and pharmacotherapy. CNS Neurosci Ther. 2010. Oct;16(5):e138-56.

[ii] Heinrichs, M. et al; Social Support and Oxytocin Interact to Suppress Cortisol and Subjective Responses to Psychological Stress. Biologic Psychology, 2003, 54: 1389-1398.

[iii] Matsushita H et al. Oxytocin mediates the antidepressant effects of mating behavior in male mice. Neurosci Res. 2010. Oct;68(2):151-3.

[iv] Lawson EA et al. Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa. J Clin Psychiatry. 2013. May;74(5):e451-7.

[v] Viero C et al. Review: Oxytocin: Crossing the bridge between basic science and pharmacotherapy. CNS Neurosci Ther. 2010. Oct;16(5):e138-56.

[vi] Hertoghe, T. Passion, Sex and Long Life, the Incredible Oxytocin Adventure.

[vii] Ohlsson B et al. Effects of long-term treatment with oxytocin in chronic constipation; a double blind, placebo-controlled pilot trial. Neurogastroenterol Motil. 2005. 17;697-704.

[viii] Louvell R et al. Oxytocin increases thresholds of colonic visceral perception in patients with irritable bowel syndrome. Gut. 1996. 39;741-747.

[ix] De Araujo AD et al. Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain. Nat Commun. 2014;5:3165.

[x] Phillips WJ et al. Relief of acute migraine headache with intravenous oxytocin: report of two cases. J Pain Palliat Care Pharmacother. 2006;20(3):25-8.

[xi] Yeomans D. Nasal oxytocin explored for migraines. Pract Neurol. 2013. May/June. 29-31.

[xii] Viero C et al. Review: Oxytocin: Crossing the bridge between basic science and pharmacotherapy. CNS Neurosci Ther. 2010. Oct;16(5):e138-56.

[xiii] MacDonald K, Feifel D. Dramatic improvement in sexual function induced by intranasal oxytocin. J Sex Med. 2012;9:1407-1410.

[xiv] IsHak WW et al. Male anorgasmia treated with oxytocin. J Sex Med. 2008;5:1022-1024.

[xv] Blaicher W et al. The role of oxytocin in relation to female sexual arousal. Gynecol Obstet Invest. 1999.;47(2):125-6.

[xvi] Van Ijzendoorn MH, et al. The impact of oxytocin administration on charitable donating is moderated by experiences of parental love-withdrawal. Fron Psychol. 2011. Oct 13;2:258.

[xvii] Tachibana M et al. Long-term administration of intranasal oxytocin is a safe and promising therapy for early adolescent boys with autism spectrum disorders. J Child Adolesc Psychopharmacol. 2013. Mar;23(2):123-7.

[xviii] Anagnostou E et al. Intranasal oxytocin in the treatment of autism spectrum disorders: A review of literature and early safety and efficacy in youth. Brain Res. 2014. http://dx.doi.org/10.1016/j.brainres.2014.01.049

[xix] Born J et al. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci. 2002 Jun;5(6):514-6.