NCT07361263

Plasma Oxytocin Response to Oral Estrogens in Healthy Controls and AVP-Deficiency

Plasma Oxytocin in Response to Oral Estradiol Valerate and Ethinylestradiol in Healthy Controls and Patients With AVP-Deficiency

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 28 (estimated)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

The PHOENIX study aims to investigate whether oral estradiol valerate (EV) and ethinylestradiol (EE) can stimulate oxytocin (OXT) and neurophysin-1 (NP-1) release in humans. The goal is to assess their potential as a safe diagnostic stimulation test for oxytocin deficiency, particularly in patients with arginine vasopressin (AVP) deficiency.

Detailed description

Oxytocin (OXT) and arginine vasopressin (AVP) are hypothalamic peptides involved in water balance and emotional regulation. Patients with AVP-Deficiency (central diabetes insipidus) often experience psychological symptoms such as anxiety and depressed mood, possibly due to coexisting OXT deficiency. Previous research showed that 3,4-Methylenedioxy-N-methylamphetamine (MDMA) can increase plasma OXT in healthy individuals but not in AVP-deficient patients, suggesting a clinically relevant OXT deficiency. However, the side effects of MDMA limit its clinical use as a diagnostic tool. Estrogen is known to stimulate OXT release via estrogen receptor β in the hypothalamus. This study evaluates whether oral estradiol valerate (EV) and ethinylestradiol (EE) can safely and effectively provoke OXT and NP-1 release, offering a potential alternative to MDMA-based tests. The study consists of two parts: Part 1 (Proof of Concept): A randomized, double-blind, cross-over trial in healthy adults to compare the stimulatory effects of EV and EE on plasma OXT and NP-1. Part 2 (Pilot Study): An open-label trial in patients with AVP-Deficiency using the estrogen compound identified as most effective in Part 1, to determine whether OXT and NP-1 responses are blunted compared to healthy controls.

Conditions

• AVP Deficiency
• Diabetes Insipidus

Interventions

Type	Name	Description
DRUG	estradiol valerate	estradiol valerate
DRUG	esthinylestradiol	estradiol valerate

Timeline

• Start date: 2026-01-09
• Primary completion: 2027-02-01
• Completion: 2027-02-01
• First posted: 2026-01-22
• Last updated: 2026-01-23

Locations

1 site across 1 country: Switzerland