How oral estrogens affect blood oxytocin in healthy people and those with AVP deficiency

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

This study will test whether two oral estrogens can trigger oxytocin release in healthy adults and in people with AVP-deficiency (central diabetes insipidus).

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: University Hospital, Basel, Switzerland (Academic / other)
• Locations: 1 site (Basel)
• Trial ID: NCT07361263 on ClinicalTrials.gov

What this trial studies

The trial first randomizes healthy adult women in a double-blind, cross-over design to receive oral estradiol valerate and ethinylestradiol while measuring plasma oxytocin and neurophysin-1 responses. The estrogen that produces the larger oxytocin response in healthy participants is then given open-label to adults with confirmed AVP-deficiency to see if their hormonal response is blunted compared with controls. Women must meet menstrual-cycle or treatment-washout criteria and the protocol excludes participants with pregnancy, breastfeeding, hormonal contraception, high BMI, significant cardiovascular or thrombotic risk, or recent investigational drug use. The approach aims to identify a safer, practical stimulation test for oxytocin deficiency as an alternative to MDMA-based provocation.

Who should consider this trial

Good fit: Adult women with regular menstrual cycles who are either healthy volunteers (Part 1) or have confirmed AVP-deficiency/central diabetes insipidus (Part 2) and who meet the study's safety and medication washout requirements.

Not a fit: People who are male, postmenopausal, pregnant or breastfeeding, using hormonal contraception or unable to pause hormone therapy, with BMI over 30, or with significant cardiovascular or thrombotic risk factors are excluded and unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this could provide a safer, practical diagnostic stimulation test for oxytocin deficiency in patients with AVP-deficiency, helping clarify causes of mood symptoms and guide care.

How similar studies have performed: Physiological and prior human data show estrogen can stimulate oxytocin and MDMA raises oxytocin in healthy people but not in AVP-deficient patients, however using oral estradiol valerate or ethinylestradiol as a diagnostic stimulation test is a novel, unvalidated approach.

Eligibility criteria

Inclusion Criteria:

Part 1

1. Adult healthy controls
2. No medication (including hormonal contraception)
3. Female patients (except post-menopausal): regular cycle (21-35 days of duration) in the last 6 months

Part 2

1. Confirmed diagnosis of AVP-Deficiency
2. Age ≥ 18 years
3. Female patients (except post-menopausal): regular cycle (21-35 days of duration) in the last 6 months or in the case of hormone replacement therapy, with a 1-week pause from the respective treatment

Exclusion Criteria:

Part 1

1. Participation in a trial with investigational drugs within 30 days
2. BMI \>30
3. Age \>50
4. Illicit substance use (except for cannabis) during the last 30 days
5. Consumption of alcoholic beverages \>15 drinks/week
6. Tobacco smoking \>10 cigarettes/day
7. Pregnancy and breastfeeding
8. Hormonal contraception
9. Migraine with and without aura
10. Any cardiometabolic, cardiovascular, and hematological diseases (including deep vein thrombosis/pulmonary embolism and thrombophilia (DVT/PE))
11. Active liver dysfunction or alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) levels 2.5 times above the normal range
12. Diagnosed chronic kidney disease (CKD) \> grade III (GRF \< 30ml/min)

Part 2

1. Participation in a trial with investigational drugs within 30 days
2. BMI \>30
3. Age \>50
4. Illicit substance use (except for cannabis) during the last 30 days
5. Consumption of alcoholic beverages \>15 drinks/week
6. Tobacco smoking \>10 cigarettes/day
7. Pregnancy and breastfeeding
8. Hormonal contraception
9. Migraine with and without aura
10. Any cardiometabolic, cardiovascular, and hematological diseases (including DVT/PE and Thrombophilia)
11. Active liver dysfunction or alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) levels 2.5 times above the normal range
12. Diagnosed CKD \> grade III (GRF \< 30ml/min)

Where this trial is running

Basel

• University Hospital Basel — Basel, Switzerland (Recruiting)

Study contacts

• Study coordinator: Andi Nikaj, MD

Conditions AVP Deficiency; Diabetes Insipidus; Oxytocin; estradiol valerate; ethinylestradiol