Trial Outcomes & Findings for Cyclical Neuroactive Steroid Changes, Arousal, and Proximal Suicide Risk: An Experimental Approach (NCT NCT04112368)

Last Updated: 2025-12-19

Results Overview

The Adult Suicidal Ideation Questionnaire (ASIQ) is a 25-item self-report questionnaire assessing suicidality. Each day, individuals rate each of 25 items on a scale from 1 (Not at All) to 6 (Extreme). Mean scores are computed, providing a single number for each day that represents the participant's mean suicidal ideation (1 to 6), with higher daily values representing more severe suicidal ideation. Perimenstrual change scores are calculated for each person in each condition as the mean of scores in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean in the midluteal phase (days +0 to +5). Therefore, positive values represent a perimenstrual increase in suicidal ideation, and negative values represent a perimenstrual decrease.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

124 participants

Primary outcome timeframe

Mean daily rating in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean daily rating in the midluteal phase (days +0 to +5)

Results posted on

2025-12-19

Participant Flow

Participant milestones

Participant milestones
Measure	Active Condition, Then Inactive Condition Beginning 7 days after ovulation, active treatment begins 7 days after ovulation with an estradiol transdermal patch (0.1 mg/24 hrs) applied to the skin weekly (spanning 14 days of treatment) along with (active) 100 mg oral micronized progesterone capsules taken twice daily by mouth for 14 days. A 1-month washout is observed. Then, beginning 7 days after ovulation, inactive placebo capsules will be taken twice daily by mouth along with the application of inactive clear patches applied to the skin weekly for 14 days.	Inactive Condition, Then Active Condition Beginning 7 days after ovulation, inactive placebo capsules will be taken twice daily by mouth along with the application of inactive clear patches applied to the skin weekly for 14 days. After completing a 1-month washout, active treatment begins 7 days after ovulation with an (active) estradiol transdermal patch applied to the skin weekly (spanning 14 days of treatment) along with (active) 100 mg oral micronized progesterone capsules taken twice daily by mouth for 14 days.
Overall Study STARTED	61	63
Overall Study COMPLETED	41	44
Overall Study NOT COMPLETED	20	19

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cyclical Neuroactive Steroid Changes, Arousal, and Proximal Suicide Risk: An Experimental Approach

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Condition, Then Inactive Condition n=61 Participants Beginning 7 days after ovulation, active treatment begins 7 days after ovulation with an estradiol transdermal patch (0.1 mg/24 hrs) applied to the skin weekly (spanning 14 days of treatment) along with (active) 100 mg oral micronized progesterone capsules taken twice daily by mouth for 14 days. A 1-month washout is observed. Then, beginning 7 days after ovulation, inactive placebo capsules will be taken twice daily by mouth along with the application of inactive clear patches applied to the skin weekly for 14 days.	Inactive Condition, Then Active Condition n=63 Participants Beginning 7 days after ovulation, inactive placebo capsules will be taken twice daily by mouth along with the application of inactive clear patches applied to the skin weekly for 14 days. After completing a 1-month washout, active treatment begins 7 days after ovulation with an (active) estradiol transdermal patch applied to the skin weekly (spanning 14 days of treatment) along with (active) 100 mg oral micronized progesterone capsules taken twice daily by mouth for 14 days.	Total n=124 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=8 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants
Age, Categorical Between 18 and 65 years	61 Participants n=8 Participants	63 Participants n=6 Participants	124 Participants n=6 Participants
Age, Categorical >=65 years	0 Participants n=8 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants
Sex: Female, Male Female	61 Participants n=8 Participants	63 Participants n=6 Participants	124 Participants n=6 Participants
Sex: Female, Male Male	0 Participants n=8 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=8 Participants	21 Participants n=6 Participants	37 Participants n=6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=8 Participants	42 Participants n=6 Participants	86 Participants n=6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=8 Participants	0 Participants n=6 Participants	1 Participants n=6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=8 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Asian	7 Participants n=8 Participants	6 Participants n=6 Participants	13 Participants n=6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=8 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Black or African American	6 Participants n=8 Participants	8 Participants n=6 Participants	14 Participants n=6 Participants
Race (NIH/OMB) White	34 Participants n=8 Participants	25 Participants n=6 Participants	59 Participants n=6 Participants
Race (NIH/OMB) More than one race	10 Participants n=8 Participants	8 Participants n=6 Participants	18 Participants n=6 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=8 Participants	16 Participants n=6 Participants	20 Participants n=6 Participants
Region of Enrollment United States	61 Participants n=8 Participants	63 Participants n=6 Participants	124 Participants n=6 Participants

PRIMARY outcome

Timeframe: Mean daily rating in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean daily rating in the midluteal phase (days +0 to +5)

Outcome measures

Outcome measures
Measure	Placebo Patch + Pills n=85 Participants Placebo patch manufactured to mimic transdermal estradiol applied weekly and placebo pills manufactured to mimic oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.	Transdermal Estradiol + Oral Micronized Progesterone n=85 Participants 0.1 mg/24hr transdermal estradiol patch applied weekly and 100 mg oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.
Perimenstrual Change in Daily Adult Suicidal Ideation Questionnaire (ASIQ) Scores	.178 Mean Score Change Standard Error .08	-.051 Mean Score Change Standard Error .05

PRIMARY outcome

The Columbia Suicide Severity Rating Scale is an interview designed to assess various aspects of suicide risk. In the present study, this questionnaire is administered daily via phone interview as part of a risk screening process. Here, we utilize a single dichotomous outcome from a single item representing suicidal planning from the C-SSRS interview: "Today, have you thought about how or when you might kill yourself?". Each day, individuals chose either "Yes" (coded as 1) or "No" (coded as 0). Perimenstrual change scores are calculated for each person in each condition as the mean of scores in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean in the midluteal phase (days +0 to +5). Therefore, positive values represent a perimenstrual increase in suicidal planning, and negative values represent a perimenstrual decrease.

Outcome measures

Outcome measures
Measure	Placebo Patch + Pills n=85 Participants Placebo patch manufactured to mimic transdermal estradiol applied weekly and placebo pills manufactured to mimic oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.	Transdermal Estradiol + Oral Micronized Progesterone n=85 Participants 0.1 mg/24hr transdermal estradiol patch applied weekly and 100 mg oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.
Perimenstrual Change in Daily Columbia Suicide Severity Rating Scale (C-SSRS) Screening Interview Planning Item Scores	-.04 Mean Score Change Standard Error .02	.021 Mean Score Change Standard Error .008

SECONDARY outcome

Hopelessness is assessed with a daily Beck Hopelessness Scale (short form), a 10-item self-report measure with true-false items that assess hopelessness and the extent of positive and negative beliefs about the future. Summed scores range from 0 to 10. Scores provide a measure of the severity of self-reported hopelessness, with higher scores representing greater hopelessness. Perimenstrual change scores are calculated for each person in each condition as the mean of scores in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean in the midluteal phase (days +0 to +5). Therefore, positive values represent a perimenstrual increase in hopelessness, and negative values represent a perimenstrual decrease.

Outcome measures

Outcome measures
Measure	Placebo Patch + Pills n=85 Participants Placebo patch manufactured to mimic transdermal estradiol applied weekly and placebo pills manufactured to mimic oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.	Transdermal Estradiol + Oral Micronized Progesterone n=85 Participants 0.1 mg/24hr transdermal estradiol patch applied weekly and 100 mg oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.
Perimenstrual Change in Daily Beck Hopelessness Scale (BHS) Short Form Scores	-.004 Mean Score Change Standard Error .003	.25 Mean Score Change Standard Error .06

SECONDARY outcome

Agitation is assessed with a daily Brief Agitation Measure (BAM), a 3-item self-report measure in which participants rate their symptoms of agitation ranging from 0 (Strongly Disagree) to 6 (Strongly Agree). Mean daily scores (ranging from 0 to 6) provide a measure of the severity of self-reported agitation, with higher scores representing greater agitation. Perimenstrual change scores are calculated for each person in each condition as the mean of scores in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean in the midluteal phase (days +0 to +5). Therefore, positive values represent a perimenstrual increase in agitation, and negative values represent a perimenstrual decrease.

Outcome measures

Outcome measures
Measure	Placebo Patch + Pills n=85 Participants Placebo patch manufactured to mimic transdermal estradiol applied weekly and placebo pills manufactured to mimic oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.	Transdermal Estradiol + Oral Micronized Progesterone n=85 Participants 0.1 mg/24hr transdermal estradiol patch applied weekly and 100 mg oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.
Perimenstrual Change in Daily Brief Agitation Measure (BAM) Scores	-.066 Mean Score Change Standard Error .015	.005 Mean Score Change Standard Error .003

Adverse Events

Transdermal Estradiol + Oral Micronized Progesterone

Serious events: 0 serious events

Other events: 77 other events

Deaths: 0 deaths

Placebo Patch + Placebo Pills

Serious events: 0 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Transdermal Estradiol + Oral Micronized Progesterone n=111 participants at risk 0.1 mg/24hr transdermal estradiol patch applied weekly and 100 mg oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.	Placebo Patch + Placebo Pills n=106 participants at risk Placebo patch (selected to match transdermal estradiol patch) applied weekly and placebo pills (blinded to match oral micronized progesterone) taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.
Skin and subcutaneous tissue disorders Skin Irritation	31.5% 35/111 • Number of events 35 • Daily using a standardized checklist during the 14 days of treatment in each condition.	11.3% 12/106 • Number of events 12 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Reproductive system and breast disorders Breast Discomfort	21.6% 24/111 • Number of events 24 • Daily using a standardized checklist during the 14 days of treatment in each condition.	10.4% 11/106 • Number of events 11 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Musculoskeletal and connective tissue disorders Joint Pain	10.8% 12/111 • Number of events 12 • Daily using a standardized checklist during the 14 days of treatment in each condition.	7.5% 8/106 • Number of events 8 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Psychiatric disorders Perceived Negative Emotional Changes	13.5% 15/111 • Number of events 15 • Daily using a standardized checklist during the 14 days of treatment in each condition.	17.9% 19/106 • Number of events 19 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Gastrointestinal disorders Nausea	14.4% 16/111 • Number of events 16 • Daily using a standardized checklist during the 14 days of treatment in each condition.	12.3% 13/106 • Number of events 13 • Daily using a standardized checklist during the 14 days of treatment in each condition.
General disorders Dizziness	8.1% 9/111 • Number of events 9 • Daily using a standardized checklist during the 14 days of treatment in each condition.	2.8% 3/106 • Number of events 3 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Eye disorders Vision Changes	4.5% 5/111 • Number of events 5 • Daily using a standardized checklist during the 14 days of treatment in each condition.	1.9% 2/106 • Number of events 2 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Respiratory, thoracic and mediastinal disorders Chest Discomfort	4.5% 5/111 • Number of events 5 • Daily using a standardized checklist during the 14 days of treatment in each condition.	2.8% 3/106 • Number of events 3 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Respiratory, thoracic and mediastinal disorders Shortness of Breath	2.7% 3/111 • Number of events 3 • Daily using a standardized checklist during the 14 days of treatment in each condition.	4.7% 5/106 • Number of events 5 • Daily using a standardized checklist during the 14 days of treatment in each condition.
General disorders Headache	15.3% 17/111 • Number of events 17 • Daily using a standardized checklist during the 14 days of treatment in each condition.	9.4% 10/106 • Number of events 10 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Skin and subcutaneous tissue disorders Venipuncture Bruising	6.3% 7/111 • Number of events 7 • Daily using a standardized checklist during the 14 days of treatment in each condition.	10.4% 11/106 • Number of events 11 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Reproductive system and breast disorders Perceived Change in Menses	9.9% 11/111 • Number of events 11 • Daily using a standardized checklist during the 14 days of treatment in each condition.	0.94% 1/106 • Number of events 1 • Daily using a standardized checklist during the 14 days of treatment in each condition.
Respiratory, thoracic and mediastinal disorders Respiratory Infection	0.90% 1/111 • Number of events 1 • Daily using a standardized checklist during the 14 days of treatment in each condition.	1.9% 2/106 • Number of events 2 • Daily using a standardized checklist during the 14 days of treatment in each condition.

Additional Information

Tory Eisenlohr-Moul

University of Illinois Chicago

Phone: 859-317-0503

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place