Neurocognitive Mechanisms of Perimenstrual Estrogen Effects on Suicidality

NCT ID: NCT06191289

Last Updated: 2025-10-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-16
• Study Completion Date: 2024-12-01

Brief Summary

This within-person, crossover, 2-condition, placebo-controlled study compares the impact of two perimenstrual conditions on severity of suicidal symptoms in females with past-month suicidality but minimal risk of imminent suicide attempt. The two conditions are (1) perimenstrual administration of estradiol and (2) natural perimenstrual withdrawal from estradiol during placebo.

Detailed Description

Previous work from our group demonstrates that perimenstrual worsening of suicidal thoughts in females is caused by normal perimenstrual withdrawal from the ovarian steroid estradiol (E2), since perimenstrual administration of E2+P4 or E2 alone prevented the perimenstrual worsening of suicidal ideation observed under placebo. In the present study, we follow up on that work with an additional mechanistic crossover trial in which E2 will be administered perimenstrually (E2 condition) or not (PBO condition) and neurocognitive mechanisms of suicidal symptom improvement will be probed.

50 (30 completers) female outpatients, with past-month suicidal ideation but minimal imminent risk for attempt, will complete self-reports and clinical interviews measuring the presence and severity of suicidal ideation in each of two conditions (A, B: order randomized across two menstrual cycles): (A) perimenstrual E2 withdrawal/depletion (under placebo), (B) perimenstrual administration of E2. A washout cycle will separate conditions. Analyses will compare the perimenstrual trajectories of symptoms and suicidality across the two conditions.

Conditions

Suicide

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Transdermal Estradiol

.1mg per 24 hours transdermal estradiol applied to the skin weekly, for 14 days.

Group Type: EXPERIMENTAL

Transdermal Estradiol

Intervention Type: DRUG

1mg/24hr transdermal estradiol for 14 days starting day 7 after positive urine luteinizing hormone test

Other Names:

Climara

Placebo

Clear patch manufactured to mimic the E2 patch applied to the skin weekly, for 14 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Weekly application of a placebo patch for 14 days starting day 7 after positive urine luteinizing hormone test

Interventions

Transdermal Estradiol

1mg/24hr transdermal estradiol for 14 days starting day 7 after positive urine luteinizing hormone test

Other Names:

Climara

Intervention Type: DRUG

Placebo

Weekly application of a placebo patch for 14 days starting day 7 after positive urine luteinizing hormone test

Intervention Type: OTHER

Eligibility 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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Tory Anne Eisenlohr-Moul

Associate Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tory A Eisenlohr-Moul, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Elizabeth Mulligan, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Katja M Schmalenberger, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

University of Illinois Neuropsychiatric Institute

Chicago, Illinois, United States

Countries

United States

Other Identifiers

2023-1560

Identifier Type: -

Identifier Source: org_study_id