Effects of Intranasal Oxytocin on Sexual Well-Being in Patients With Arginine Vasopressin Deficiency and Healthy Controls

Disruption of the hypothalamic-pituitary axis, caused by inflammation, tumors, or head trauma, can result in arginine vasopressin (AVP) deficiency (AVP-D), formerly known as central diabetes insipidus (cDI). This condition is characterized by polyuria and polydipsia, leading to significant disruptions in the body's fluid balance. Desmopressin, an AVP receptor analogue, is the standard treatment for AVP-D and effectively mitigates these physical symptoms.

However, patients with AVP-D frequently report residual psychological symptoms that remain unaddressed despite desmopressin therapy. These include impaired emotion recognition, reduced empathy, heightened anxiety, social interaction difficulties, and decreased sexual desire-all of which significantly affect their quality of life. Recent data from an international survey of over 1,000 patients with AVP-D reinforce these findings, highlighting the psychosocial burden of this condition.

Oxytocin (OXT), a neuropeptide closely associated with AVP in terms of anatomical location and function, is known to play a critical role in social, emotional, and behavioral regulation. As a "pro-social" hormone, OXT fosters trust, intimacy, attachment, and pair bonding, while also mitigating stress. The proximity of the AVP and OXT systems within the brain suggests that disruptions in one could potentially lead to deficiencies in the other. Supporting this hypothesis, recent research using a novel stimulation test with MDMA demonstrated an OXT deficiency in patients with AVP-D, offering a potential explanation for their observed psychopathology.

OXT's influence extends to sexual well-being, where it has been shown to enhance bonding, intimacy, and the emotional aspects of sexual relationships. Elevated OXT levels are observed during labor, lactation, and sexual arousal, and studies suggest correlations between OXT and orgasm intensity, sexual satisfaction, and partner attachment. While previous studies have examined OXT's effects on social and emotional behavior in healthy individuals, its therapeutic potential in addressing psychological and sexual well-being in AVP-D patients remains unexplored.

This study aims to investigate whether intranasal OXT administration can improve sexual well-being, intimacy, and pair bonding in patients with AVP-D. By addressing an unrecognized OXT deficiency, this research seeks to fill a critical gap in understanding and managing the psychosocial challenges associated with AVP-D.

The trial employs a randomized, double-blind, placebo-controlled, cross-over design and consists of two parts:

1. Part A involves a seven-day treatment with intranasal OXT (24 IU) or placebo in patients with AVP-D and their partners. Participants will self-assess their sexual well-being and intimacy at baseline and after each treatment period, with a three-week washout period between treatments.

2. Part B evaluates the acute effects of a single intranasal OXT dose (24 IU) or placebo on sexual arousal, empathy, fear perception, and hormonal responses to visual stimuli in both single and partnered patients with AVP-D, compared to healthy controls.

This comprehensive approach will provide insights into both the long-term and immediate impacts of OXT therapy, with the ultimate goal of improving quality of life for patients with AVP-D.