Unique Effects of Perimenstrual Estradiol or Progesterone Supplementation on Perimenstrual Suicidality
Condition: Suicidal Ideation
MeSH terms: Suicidal Ideation
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Transdermal Estradiol + Placebo; Oral Micronized Progesterone + Placebo; Placebos
Intervention type(s): Drug; Drug; Drug
Intervention description(s): .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.
Other intervention name(s): Climara; sugar pill; Prometrium; placebo patch; sugar pill; placebo patch
Intervention MeSH terms: Estradiol; Progesterone
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Crossover 3-condition placebo-controlled trial
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: steroid hormones; estradiol; estrogen; progesterone; depression; suicide