From Francesca Galbiati, M.D. – Assistant Professor University of California San Francisco and PWN contributor – Oxytocin is a neurohormone (meaning that it acts both as a neurotransmitter in the brain and as a hormone on target organs in the body) produced by the hypothalamus and secreted both to the brain and the blood circulation. Oxytocin secretion to distant target organs involves its transport to the posterior pituitary gland via the pituitary stalk.
Oxytocin is classically known for its role in labor and breastfeeding; however, a growing body of literature has demonstrated oxytocin’s role in several physiologic domains both in animal models and humans. Oxytocin, in fact, regulates metabolism, mood, social functioning, sexual function, and bone and muscular health. It is intuitive, then, that an oxytocin deficiency could be clinically relevant in both sexes.
Given the anatomy of oxytocin production, storage, and secretion, many studies have focused on patients with hypothalamic and pituitary damage, like patients with cranial tumors and/or extensive cranial surgeries. Particular emphasis is put on arginine-vasopressin deficiency (AVP-D, formerly called central diabetes insipidus). Vasopressin is, in fact, produced, stored, and secreted in close proximity to oxytocin, and it is likely that when vasopressin is deficient, oxytocin will also be affected. Patients with AVP-D have been shown to be at the greatest risk for a coexisting oxytocin deficiency, which could contribute to the well-documented worse quality of life observed in patients with hypopituitarism despite optimal hormonal replacement. Oxytocin deficiency in this population may also contribute to worse anxiety and depressive symptoms, as well as worse bone health, compared to patients with pituitary deficiencies but not AVP-D.
Thus, it is natural to recognize oxytocin deficiency as a clinical entity and consider that an oxytocin deficiency may be present when we approach our patients with hypothalamic and pituitary damage. There are, however, several challenges in diagnosing and treating oxytocin deficiency. Oxytocin is difficult to measure in the blood, and a diagnostic test (like a stimulation test) is not yet available, despite several studies have been investigating potential stimuli.
Oxytocin treatment is available as an intranasal spray, but it is currently not FDA-approved. Case reports and small studies using oxytocin or carbetocin (a longer-acting oxytocin analog) have shown improvement in various clinical symptoms in patients with hypothalamic and pituitary damage. However, there is no strong evidence, with some studies showing benefits of oxytocin treatment and others not. Conflicting findings could be explained by the different formulations, doses, frequency of administration, and duration of treatment with oxytocin.
In conclusion, it is not unlikely that in the upcoming years, cortisol, thyroid, sex hormones, growth hormone, and vasopressin replacements will be also accompanied by oxytocin replacement.
Note from the editors:
Learn about clinical trials. To advance oxytocin-based therapeutics in patients with hypothalamic and pituitary damage, clinical trials of oxytocin replacement are ongoing in the United States (NCT04789148) and Europe (NCT06036004, NCT06676774, NCT06808516).
If you’d like to learn more these two links will take you to two relevant papers: One from Science Direct, Endocrinología Diabetes y Nutritción Oxytocin in hypopituitarism: What do we know? and from Oxford Academic Encoring review The Oxytocin System and Implications for Oxytocin Deficiency in Hypothalamic-Pituitary Disease
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