A Phase 2 interventional study of Transdermal Estradiol and Placebo in Suicide, sponsored by University of Illinois at Chicago. Terminated at 1 site in United States. Open to female participants aged 20 Years to 40 Years. Per ClinicalTrials.gov, last updated 2025-10-29.
Sponsored by University of Illinois at Chicago · Phase 2, Interventional, and Basic science
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.
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.
701 studies on the registry are indexed under Suicide; 183 are open to participants now.
This study's enrollment of 11 is below the median of 104 across 560 interventional studies indexed under Suicide.
Browse Suicide studies →University of Illinois at Chicago is the lead sponsor of 515 studies on the registry; 133 are open to participants now.
Of its 31 completed or terminated interventional studies of FDA-regulated products, 18 (58%) have results posted.
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.1mg per 24 hours transdermal estradiol applied to the skin weekly, for 14 days.
Drug: Transdermal Estradiol
Clear patch manufactured to mimic the E2 patch applied to the skin weekly, for 14 days.
Other: Placebo
1mg/24hr transdermal estradiol for 14 days starting day 7 after positive urine luteinizing hormone test Other Names: Climara
Weekly application of a placebo patch for 14 days starting day 7 after positive urine luteinizing hormone test
Early-Luteal-to-Perimenstrual Worsening of Daily Passive Suicidal Ideation (PSI)
Three daily survey questions assessing PSI will be administered each day (i.e., "I wished I were dead", "I wish I could go to sleep and not wake up", "I thought that life was not worth living"; scale from 1 (Not at All) to 5 (Extremely)). Composite mean scores for these 3 items are computed, providing a single number for each day, with higher daily values representing more severe PSI. Early-luteal-to-perimenstrual worsening of daily PSI is estimated for each person in each condition as the mean of scores in the perimenstrual phase (Days -3 to +1 relative to menses onset) minus the mean in the early luteal phase (Days +2 to +6 relative to the luteinizing hormone surge at day 0).
Time frame: Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6
Early-Luteal-to-Perimenstrual Worsening of Daily Active Suicidal Ideation (ASI)
Three daily survey questions assessing ASI will be administered each day (i.e., "I thought about killing myself", "I wanted to kill myself", "I had the urge to kill myself"; scale from 1 (Not at All) to 5 (Extremely)). Composite mean scores for these 3 items are computed, providing a single number for each day, with higher daily values representing more severe ASI. Early-luteal-to-perimenstrual worsening of daily ASI is estimated for each person in each condition as the mean of scores in the perimenstrual phase (Days -3 to +1 relative to menses onset) minus the mean in the early luteal phase (Days +2 to +6 relative to the luteinizing hormone surge at day 0).
Time frame: Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6
Early-Luteal-to-Perimenstrual Increase in the Probability of Daily Suicidal Planning (SP)
Two questions from the ASIQ assessing SP will be administered each day in an adapted daily format (i.e., "I thought about how I might kill myself", "I thought about when I might kill myself"; scale from 1 (Not at All) to 5 (Extremely)). Daily dichotomous scores will be derived such that if either of these two items are endorsed with a score higher than 1 (not at all) on a given day, the composite score will be 1 (otherwise the score will be 0) for that day. Early-luteal-to-perimenstrual increase in the probability of daily SP is estimated for each person in each condition as the mean of dichotomous daily scores in the perimenstrual phase (Days -3 to +1 relative to menses onset) minus the mean of dichotomous scores in the early luteal phase (Days +2 to +6 relative to the luteinizing hormone surge at day 0).
Time frame: Mean daily dichotomous outcome (ranging from 0-1) in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean in the early luteal phase (Days +2,
Perimenstrual Reward Positivity (RewP)
The reward positivity (RewP), measured with electroencephalography, is an event-related potential (ERP) component index of neural responsiveness to receipt of reward. Approximately 300 milliseconds (ms) after computerized task feedback indicating monetary reward, the ERP at frontocentral recording sites is characterized by a relative positivity; an apparent negativity is observed following feedback indicating monetary loss. The relative difference in ERP amplitudes in response to reward as compared to loss is referred to as the Reward Positivity. During each experimental perimenstrual phase (E2 vs. placebo), participants will participate in a gambling task while EEG is used to record the averaged RewP amplitude.
Time frame: Mean RewP amplitude in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline)
Early-Luteal-to-Perimenstrual Worsening of daily self-reported anhedonia
Three daily items assessing anhedonia will be administered each day (i.e., "Didn't enjoy things", "Had less interest in things", and "Felt unmotivated to do things"; scale from 1 (Not at All) to 6 (Extreme)). Composite mean scores for these 3 items are computed for each day, providing a single number for each day, with higher daily values representing more anhedonia. Early-luteal-to-perimenstrual worsening of daily anhedonia is estimated for each person in each condition as the mean of scores in the perimenstrual phase (Days -3 to +1 relative to menses onset) minus the mean in the early luteal phase (Days +2 to +6 relative to the luteinizing hormone surge at day 0).
Time frame: Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6
Early-Luteal-to-Perimenstrual change (improvement) in daily N-Back performance
Participants will complete a daily at-home working memory computerized task: the N-Back task. Number of "hits" (i.e., correctly indicated targets) in this task will serve as our measure of daily working memory behavioral performance, with higher daily values representing better working memory performance. Early-luteal-to-perimenstrual change (calculated as improvement) of daily N-Back scores is estimated for each person in each condition as the mean of scores in the perimenstrual phase (Days -3 to +1 relative to menses onset) minus the mean in the early luteal phase (Days +2 to +6 relative to the luteinizing hormone surge at day 0). Therefore, positive values represent a perimenstrual improvement in working memory performance, and negative values represent a perimenstrual worsening.
Time frame: Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6
Early-Luteal-to-Perimenstrual Worsening of daily self-reported working memory failures (WMF)
Three questions assessing WMF will be administered each day (i.e., "Had difficulty concentrating", "I forgot things", and "I got distracted easily"; scale from 1 (Not at All) to 6 (Extreme)). Composite mean scores for these 3 items are computed daily, providing a single number for each day, with higher daily values representing more severe WMF. Early-luteal-to-perimenstrual worsening of WMF is estimated for each person in each condition as the mean of scores in the perimenstrual phase (Days -3 to +1 relative to menses onset) minus the mean in the early luteal phase (Days +2 to +6 relative to the luteinizing hormone surge at day 0).
Time frame: Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6
This study is terminated, as verified in Oct 2025. You cannot join it, but the record below documents what was studied.
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University of Illinois at Chicago