Melatonin as a possible stimulus to unmask an oxytocin deficient state in hypopituitarism and hypothalamic damage.

Context

Increasing evidence supports the presence of oxytocin deficiency (OXT-D) in hypopituitarism and hypothalamic damage (HHD). Identifying an applicable and reliable test to diagnose an OXT-D is an unmet need. Melatonin might be a candidate for such a test as it regulates OXT release in animals.

Objective

To examine the effects of melatonin on OXT release in HHD compared to healthy controls (HC) and to describe psychopathology, sexual function and quality of life (QoL) and their associations with OXT.

Methods

This proof-of-concept study (NCT05319301) included 20 participants with HHD (11 females) and 20 HC (11 females). Blood samples were collected over 120 minutes to assess plasma OXT. Linear mixed-effects regression model was used to evaluate the change in OXT in response to melatonin in HHD compared to HC.

Results

Melatonin significantly increased OXT at T90 vs. T0 in HC compared to HHD group (difference 14.57 pg/mL 26% increase, 95%IC 1.90 to 27.23, p=0.02). HHD group had more depression symptoms, alexithymia, impaired sexual function and worse QoL compared to HC. The mean percentage change in OXT from T0 to T90 was negatively associated with depressive and alexithymia symptoms in HHD group and anxiety in both groups.

Conclusion

The reduced OXT response after melatonin in HHD, supports the existence of an impaired OXT response at least in a subset of patients with HHD. The associations between OXT changes and psychopathology suggest its role in mood and QoL. These findings support further investigation into melatonin's role as a diagnostic tool to address OXT-D.

© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.