Unique Effects of Perimenstrual Estradiol or Progesterone Supplementation on Perimenstrual Suicidality

NCT ID: NCT03498313

Last Updated: 2022-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-27
• Study Completion Date: 2021-05-09

Brief Summary

This within-person, crossover, 3-condition, placebo-controlled study compares the impact of three perimenstrual conditions on severity of suicidal symptoms in females with past-month suicidality but minimal risk of imminent suicide attempt. The three conditions are (1) perimenstrual withdrawal from estradiol only (during progesterone stabilization), (2) perimenstrual withdrawal from progesterone only (during estradiol stabilization), and (3) perimenstrual withdrawal from both estradiol and progesterone 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 steroids estradiol (E2) and progesterone (P4), since perimenstrual stabilization of E2+P4 prevented the perimenstrual worsening of suicidal ideation observed under placebo. In the present study, we follow up on that work with an additional mechanistic trial in which E2 and P4 will be stabilized in separate arms of the study.

60 (30 completers) female outpatients, with past-month suicidal ideation but minimal imminent risk for attempt, will complete self-reports and clinical interviews measuring presence and severity of suicidal ideation in each of three conditions (A, B, C: order randomized across three menstrual cycles): (A) perimenstrual E2/P4 withdrawal (under placebo), (B) perimenstrual P4 withdrawal (exogenous stabilization of E2 only), and (C) perimenstrual E2 withdrawal (exogenous stabilization of P4 only). A washout cycle will separate conditions. Analyses will compare the perimenstrual trajectories of symptoms and suicidality across the three conditions.

Conditions

Suicidal Ideation

Study Design

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

Study Groups

Transdermal Estradiol + Placebo

.1mg per 24 hours transdermal estradiol applied to the skin weekly, and sugar pill manufactured to mimic the progesterone pills taken twice daily by mouth, for 14 days.

Group Type: EXPERIMENTAL

Transdermal Estradiol + Placebo

Intervention Type: DRUG

.1mg/24hr transdermal estradiol for 14 days starting day 7 after positive urine luteinizing hormone test, plus twice daily placebo pills during the same time frame.

Oral Micronized Progesterone + Placebo

100 mg oral micronized progesterone pill taken twice daily by mouth, and clear patch manufactured to mimic the E2 patch applied to the skin weekly, for 14 days.

Group Type: EXPERIMENTAL

Oral Micronized Progesterone + Placebo

Intervention Type: DRUG

100mg oral micronized progesterone twice daily for 14 days starting day 7 after positive urine luteinizing hormone test, plus weekly application of a placebo patch during the same time frame.

Placebos

Sugar pill designed to mimic the P4 pills taken twice daily by mouth, and clear patch manufactured to mimic the E2 patch applied to the skin weekly, for 14 days.

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Twice daily placebo pills for 14 days starting day 7 after positive urine luteinizing hormone test, plus weekly application of a placebo patch during the same time frame.

Interventions

Transdermal Estradiol + Placebo

.1mg/24hr transdermal estradiol for 14 days starting day 7 after positive urine luteinizing hormone test, plus twice daily placebo pills during the same time frame.

Intervention Type: DRUG

Oral Micronized Progesterone + Placebo

100mg oral micronized progesterone twice daily for 14 days starting day 7 after positive urine luteinizing hormone test, plus weekly application of a placebo patch during the same time frame.

Intervention Type: DRUG

Placebos

Twice daily placebo pills for 14 days starting day 7 after positive urine luteinizing hormone test, plus weekly application of a placebo patch during the same time frame.

Intervention Type: DRUG

Other Intervention Names

Climara; sugar pill; Prometrium; placebo patch; sugar pill; placebo patch

Eligibility Criteria

Inclusion Criteria

• Ability to adhere to medication regimen
• Speaks English
• Assigned female at birth with intact ovaries
• Premenopausal
• Normal menstrual cycles between 25-35 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 18.00-29.99)
• 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 that may interfere with the aims of the study or make the experimental protocol unsafe, 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 current diagnosis of major depressive episode with peripartum onset (current episode), and must not be currently receiving treatment for 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.
• Must not test positive for (unprescribed) opioid use, methamphetamine use, or cocaine use at the start of an experimental condition.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Tory Anne Eisenlohr-Moul

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tory A Eisenlohr-Moul, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

University of Illinois Neuropsychiatric Institute

Chicago, Illinois, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R00MH109667

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2018-0189

Identifier Type: -

Identifier Source: org_study_id