Melatonin as a Possible Stimulus to Unmask an Oxytocin-Deficient State in Hypopituitarism and Hypothalamic Damage

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

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

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

MEL significantly increased OXT at T90 vs T0 in HCs compared to the HHD group (difference 14.57 pg/mL 26% increase; 95% CI, 1.90-27.23; P = .02). The HHD group had more depression symptoms, alexithymia, impaired sexual function, and worse QoL compared to HCs. The mean percentage change in OXT from T0 to T90 was negatively associated with depressive and alexithymia symptoms in the HHD group and anxiety in both groups.

The reduced OXT response after MEL 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 MEL's role as a diagnostic tool to address OXT-D.