Unique Effects of Perimenstrual Estradiol or Progesterone Supplementation on Perimenstrual Suicidality
Condition: Suicidal Ideation
MeSH terms: Suicidal Ideation
Intervention: Transdermal Estradiol + Placebo; Oral Micronized Progesterone + Placebo; Placebos
Intervention description: .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.; 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.; 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 MeSH terms: Estradiol; Progesterone
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Crossover 3-condition placebo-controlled trial
Masking: Double (Participant, Investigator)
Masking description: double-blind
Enrollment: 60.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: steroid hormones; estradiol; estrogen; progesterone; depression; suicide

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.
    

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.