Effects of estrogen on suicidal thoughts during the menstrual cycle

Clarifying the Endocrinology of Acute Risk 4 (CLEAR-4): Neurocognitive Mechanisms of Perimenstrual Estrogen Effects on Suicidality

Phase 2 Interventional University of Illinois at Chicago · NCT06191289

This study is testing how changes in estrogen levels during the menstrual cycle affect suicidal thoughts in women who have recently experienced these feelings.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment50 (estimated)
Ages20 Years to 40 Years
SexFemale
SponsorUniversity of Illinois at Chicago Academic / other
Locations1 site (Chicago, Illinois)
Trial IDNCT06191289 on ClinicalTrials.gov

What this trial studies

This interventional study investigates how perimenstrual estrogen levels affect suicidal symptoms in females with recent suicidal ideation. Participants will undergo a crossover design where they will experience two conditions: one with perimenstrual administration of estradiol and another with natural withdrawal from estradiol during a placebo phase. The study aims to understand the neurocognitive mechanisms behind changes in suicidal thoughts related to these hormonal fluctuations. A total of 50 female outpatients will complete self-reports and clinical interviews to measure their symptoms across the two conditions.

Who should consider this trial

Good fit: Ideal candidates are premenopausal females with a history of recent suicidal thoughts and minimal imminent risk for suicide attempts.

Not a fit: Patients who are pregnant, breastfeeding, or using hormonal contraceptives may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for women experiencing suicidal ideation linked to hormonal changes.

How similar studies have performed: Previous studies have indicated that hormonal treatments can influence suicidal ideation, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Ability to adhere to medication regimen
* Speaks English
* Assigned female at birth with intact ovaries
* Premenopausal
* Normal menstrual cycles between 24-32 days
* Under current care of an outpatient mental health provider with visits occurring at least once every 3 months.
* At least 1 year postpartum.
* Willing to use a barrier method of birth control during the study.
* Normal weight (BMI between 18-29)
* Must report at least some recent suicidal ideation (in the past month) at the time of recruitment.
* Must be categorized as having acceptably low imminent risk for suicidal crisis/attempt by a licensed clinical psychologist utilizing evidence-based clinical and research guidelines for imminent suicide risk management.

Exclusion Criteria:

* Must not be pregnant, breastfeeding, or trying to become pregnant.
* Must not be taking any form of exogenous hormones or hormonal intrauterine device, and must have ended previous use of hormonal preparations at least one month prior to the study.
* Must not have a personal history of any chronic medical condition, including but not limited to metabolic or autoimmune disease, epilepsy, endometriosis, cancer, diabetes, cardiovascular, gastrointestinal, hepatic, renal, or pulmonary disease, and no personal or first degree family history of thromboembolic events.
* Any current cigarette smoking is exclusionary.
* Must not report a history of clinical diagnosis or treatment for postpartum depression or premenstrual dysphoric disorder (Note: Premenstrual Dysphoric - - - Disorder diagnosis must have been made based on prospective daily ratings).
* Must not report any history of manic episode, any history of psychotic symptoms, or current substance use disorder.

Where this trial is running

Chicago, Illinois

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions SuicideMENSTRUAL CYCLEHORMONESESTROGENREWARDEXECUTIVE FUNCTION
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.