PTSDEarly Phase 1NCT03973229

Neuroendocrine Risk for PTSD in Women

A Early Phase 1 study testing Estradiol patch in people with PTSD and Trauma, run by Emory University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will test for effects of estradiol (E2) on PTSD symptoms and functional magnetic resonance imaging (fMRI) indicators of stress vulnerability, in naturally-cycling women who are not using hormonal birth control. Read more about this study

Who is it for?: Ages 18 to 35 years, women only
Conditions the study is for: PTSD, Trauma
What is being tested?: Estradiol patch
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 127 participants
Where: 1 siteUnited States
Study dates: 11 Nov 2019to 30 Apr 2025
Phase: Early Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 35 years
Women only
No healthy volunteers
Adult

Who may be able to join

African American women
A menstrual period within the past 60 days
Able and willing to give informed consent
Must have a smart phone and willing to install the Clue app

Who cannot join

Women currently taking any form of hormone-based birth control or other hormonal supplement
Women who are pregnant or breastfeeding
Current psychoactive medication use
Nicotine use or smoking
Hypercoagulable conditions
History of embolism

Show all 9Show fewer

Current symptoms of psychosis or bipolar disorder
History of major head injury or neurological disorder
Weight >250lbs (a maximum weight to allow for participants to fit comfortably inside the bore of the MRI machine) and typical physical contraindications for MRI such as metal implants

Trial locations and contacts

1 site in 1 country.

United States1 site

Grady Memorial Hospital
Atlanta, Georgia, 30303

Other trials in United States

About this study

Official title: The LOW E2 STUDY- Neuroendocrine Risk Mechanisms for Post-traumatic Stress Disorder in Women

PTSD: Women who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for PTSD
Trauma-Exposed (TC): Women matched for age and trauma exposure severity but without PTSD
Healthy Control (HC): Women matched for age, but without trauma history or psychiatric disorder (self-reported)

Women will be recruited through Grady Trauma Project (GTP), a large longstanding study of civilian trauma and PTSD conducted at Grady Memorial Hospital in Atlanta, Georgia.

Read the detailed description

The majority of Americans will experience a traumatic event during their lifetimes. However, women are twice as likely as men to experience negative psychiatric outcomes following trauma, including post-traumatic stress disorder (PTSD) and depression. The reason for the increased prevalence in women is unclear, partially because of the historical lack of investigation of females in both human and pre-clinical animal research. The researchers propose to investigate the role of sex hormones in contributing to women's risk for PTSD. The study will investigate relationships between trauma exposure and women's menstrual cycle, examining key events in the cycle, including menstruation, ovulation, and mood changes. The study will then examine relationships between the level of naturally-cycling estradiol (E2; the primary female sex hormone), and brain-based measures of stress vulnerability. This includes amygdala hyper-reactivity to threat.

The trial will study if trauma-exposed women with lower E2 levels during the luteal phase will report greater PTSD symptoms, and show more stress-vulnerable patterns of brain function. It will also examine the effects of exogenous application of estrogen on PTSD symptoms.

Women will begin tracking their cycle using a free and widely-used cycle-tracking smartphone app "Clue" for one full menstrual cycle.

For Study Aims 1 \& 2 (N=120): Participants will be contacted on the first day of their menstrual period in the second cycle, and scheduled for an MRI with a 4-day window (early follicular phase). Participants will be randomized to begin with either the E2 or placebo patch. The will receive an E2 or placebo patch 1 day prior to the MRI visit, with a blood draw on the morning of the MRI visit (to assess hormone levels), 1 hour prior to scanning. On the first day of the third cycle (onset of menses), women will all be scheduled for their second MRI visit. Participants will experience the opposite condition from their first MRI scan. They will receive an E2 or placebo patch 1 day prior to the MRI visit in the afternoon, with a blood draw on the morning of the MRI visit, 1 hour prior to scanning.
For Study Aim 3 (N=120): Participants will begin daily urine ovulation tests on Day 11 of their cycle, and will record the results in Clue. When participants record a positive ovulation test during the second month of cycle monitoring, they will be contacted to schedule their MRI visit 5-7 days following ovulation (during the luteal phase). The experimental protocol will otherwise be the same as in Aims 1 and 2, with participants randomized to either E2 or placebo at the first visit and returning the next month for the other condition.

The scientific premise of this study is that low E2 may contribute to stress vulnerability in women. Findings may aid in the development of treatments that will enhance women's mental health outcomes following trauma.

Conditions: PTSD, Trauma
Being tested: Estradiol patch, Placebo patch
Keywords: Estrogen, Stress Disorder
Medical subject headings: Stress Disorders, Post-Traumatic, Wounds and Injuries, Stress Disorders, Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Estradiol patchDrug
Estradiol (E2) patches at a dose of 100ug will be applied 24-48 hours before the MRI scan is performed.
Placebo patchOther
Placebo patch identical to the estradiol patch will be applied 24-48 hours before the MRI scan is performed.

Study groups in NCT03973229
Study group	Role	What they receive
Cohort 1: PTSD Receiving Estradiol then Placebo	Experimental	Participants with PTSD will record their first cycle with the Clue app. They will receive the estradiol patch during the second cycle, and the placebo patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 1: PTSD Receiving Placebo then Estradiol	Experimental	Participants with PTSD will record their first cycle with the Clue app. They will receive the placebo patch during the second cycle, and the estradiol patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 1: Trauma without PTSD Receiving Estradiol then Placebo	Active comparator	Participants with trauma exposure will record their first cycle with the Clue app. They will receive the estradiol patch during the second cycle, and the placebo patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 1: Trauma without PTSD Receiving Placebo then Estradiol	Active comparator	Participants with trauma exposure will record their first cycle with the Clue app. They will receive the placebo patch during the second cycle, and the estradiol patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 1: Healthy Controls Receiving Estradiol then Placebo	Active comparator	Participants without trauma history or psychiatric disorder will record their first cycle with the Clue app. They will receive the estradiol patch during the second cycle, and the placebo patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 1: Healthy Controls Receiving Placebo then Estradiol	Active comparator	Participants without trauma history or psychiatric disorder will will record their first cycle with the Clue app. They will receive the placebo patch during the second cycle, and the estradiol patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 2: PTSD Receiving Estradiol then Placebo	Experimental	Participants with PTSD will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the estradiol patch before getting the MRI. They will apply the placebo patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 2: PTSD Receiving Placebo then Estradiol	Experimental	Participants with PTSD will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the placebo patch before getting the MRI. They will apply the estradiol patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 2: Trauma Control Receiving Estradiol, then Placebo	Active comparator	Participants with trauma exposure will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the estradiol patch before getting the MRI. They will apply the placebo patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 2: Trauma Control Receiving Placebo then Estradiol	Active comparator	Participants with trauma exposure will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the placebo patch before getting the MRI. They will apply the estradiol patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 2: Healthy Control Receiving Estradiol then Placebo	Active comparator	Participants without trauma history or psychiatric disorder will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the estradiol patch before getting the MRI. They will apply the placebo patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch
Cohort 2: Healthy Control Receiving Placebo then Estradiol	Active comparator	Participants without trauma history or psychiatric disorder will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the placebo patch before getting the MRI. They will apply the estradiol patch during the third cycle. Receives: Drug: Estradiol patch; Other: Placebo patch

What is being measured

The primary outcome is the main question the study is designed to answer.

Amygdala Response to Fearful Faces Stimuli
Responses to threat cues are assessed by functional magnetic resonance imaging (fMRI) responses as participants view 15 blocks each of fearful face and neutral face stimuli, while amygdala reactivity is measured. The amygdala is separated in the right and left hemispheres, and subdivided into the basolateral amygdala and central amygdala. Across voxels in each region a contrast estimate of Fearful > Neutral faces was extracted. The contrast estimate is a standard reporting format for task-based fMRI data, and reflects the magnitude of blood oxygen level dependent (BOLD) activation difference between two experimental conditions. Contrast estimates are an arbitrary, unitless comparison of fMRI BOLD signal units of one experimental condition versus another (threat vs. neutral stimuli). Higher values indicate greater amygdala reactivity to threat cues (vs. neutral cues), a PTSD-linked response pattern. Negative values indicate stronger amygdala reactivity to neutral cues than threat cues.
Measured: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)
Amygdala Response to Fear Conditioning Task
Indicators of fear conditioning are assessed by fMRI during the fear conditioning tasks. Deficits in fear inhibition have been present in persons with PTSD and during phases of the ovarian cycle. The amygdala is subdivided into the basolateral amygdala and central amygdala. Across voxels in each region a contrast estimate of conditioned stimulation (CS)+ (conditioned threat cues) > CS- (conditioned safety cues) was extracted. The contrast estimate reflects the magnitude of BOLD activation difference between two experimental conditions. Contrast estimates are an arbitrary, unitless comparison of fMRI BOLD signal units of one experimental condition versus another. Positive values indicate strong responsivity to conditioned threats, which could indicate either fear- or memory-related responses. Strong positive values indicate high responsivity to the conditioned threat (CS+), a pattern often associated with PTSD. Negative values indicate greater responsivity to safety cues (CS-).
Measured: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)
Ventromedial Prefrontal Cortex (vmPFC) Activation During the Fear Extinction Task
Indicators of fear extinction are assessed by fMRI during the fear extinction tasks. Fear extinction is impaired in persons with PTSD and depends on the vmPFC and its inhibition of amygdala responses to threat stimuli. The vmPFC region is defined using the anatomical boundaries of Brodmann area 25 (BA25). Across voxels in this region, a mean contrast estimate of CS+ > CS- in late extinction was extracted. The contrast estimate reflects the magnitude of BOLD activation difference between experimental conditions. Contrast estimates are a unitless comparison of fMRI BOLD signal units of one experimental condition versus another. These values indicate responsivity to conditioned threats. For the vmPFC, a positive value often indicates regulation of emotion or fear now that the threat cues have been extinguished. Strong positive values indicate higher engagement of this region to the conditioned threat (CS+). Negative values indicate higher engagement of this region to safety cues (CS-).
Measured: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)

Secondary outcomes (2)

PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (PCL-5)
The severity of self-reported PTSD symptoms will be assessed with the PCL-5. The PCL-5 asks participants to recall the worst stressful event that is currently bothering them the most. Keeping this event in mind, participants respond to 20 questions indicating how bothered they have been by PTSD symptoms. Responses are on a 5-point scale, where 0 = not bothered at all and 4 = extremely bothered. Total raw scores range from 0 to 80 where higher scores indicate greater distress from PTSD symptoms.
Measured: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)
Beck Depression Inventory (BDI)
The BDI-II is a 21-item instrument assessing depression. Respondents indicate how severe their feelings of depression symptoms are on a scale of 0 (not present) to 3 (most severe). Total raw scores range from 0 to 63, with higher scores indicating greater severity of depression.
Measured: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Nov 201930 Apr 2025

First posted4 Jun 2019
Study start11 Nov 2019
Primary completion30 Apr 2025
Study completion30 Apr 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for PTSDStudies of the same condition, open and under way.
More trials run by Emory UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Model description: Women will participate in one cycle with the estrogen patch and one cycle with the placebo patch. Each cohort will include 40 participants in each of the three study arms for a total of 240 participants.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 127 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03973229
Sponsor's protocol ID: IRB00103595
Other IDs: 1R01MH117009-01A1
Status last verified: Jun 2026
First submitted: 30 May 2019
Last updated: 22 Jul 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: There is an agreement with the National Institute of Mental Health (NIMH) to share deidentified data with Research Domain Criteria (RDoC) database (a centralized NIH database). Raw neuroimaging data and behavioral data for the 3 tasks (Fearful Faces, Fear Conditioning, Fear Extinction), T1 structural brain images, non-identifying demographics, PTSD Checklist for DSM-5 (PCL-5), and Beck Depression Inventory (BDI) will be shared.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The LOW E2 STUDY- Neuroendocrine Risk Mechanisms for Post-traumatic Stress Disorder in Women
ClinicalTrials.gov ID: NCT03973229
Acronym / sponsor ID: IRB00103595
Conditions: PTSD, Trauma
Keywords: Estrogen, Stress Disorder
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 127 participants (actual)
Lead sponsor: Emory UniversityUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH)
Study start: 11 Nov 2019 (actual)
Primary completion: 30 Apr 2025 (actual)
Study completion: 30 Apr 2025 (actual)
First posted: 4 Jun 2019 (actual)
Results: Posted 22 Jul 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

PTSD: Women who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for PTSD
Trauma-Exposed (TC): Women matched for age and trauma exposure severity but without PTSD
Healthy Control (HC): Women matched for age, but without trauma history or psychiatric disorder (self-reported)

Women will be recruited through Grady Trauma Project (GTP), a large longstanding study of civilian trauma and PTSD conducted at Grady Memorial Hospital in Atlanta, Georgia.

Detailed description

Women will begin tracking their cycle using a free and widely-used cycle-tracking smartphone app "Clue" for one full menstrual cycle.

For Study Aims 1 \& 2 (N=120): Participants will be contacted on the first day of their menstrual period in the second cycle, and scheduled for an MRI with a 4-day window (early follicular phase). Participants will be randomized to begin with either the E2 or placebo patch. The will receive an E2 or placebo patch 1 day prior to the MRI visit, with a blood draw on the morning of the MRI visit (to assess hormone levels), 1 hour prior to scanning. On the first day of the third cycle (onset of menses), women will all be scheduled for their second MRI visit. Participants will experience the opposite condition from their first MRI scan. They will receive an E2 or placebo patch 1 day prior to the MRI visit in the afternoon, with a blood draw on the morning of the MRI visit, 1 hour prior to scanning.
For Study Aim 3 (N=120): Participants will begin daily urine ovulation tests on Day 11 of their cycle, and will record the results in Clue. When participants record a positive ovulation test during the second month of cycle monitoring, they will be contacted to schedule their MRI visit 5-7 days following ovulation (during the luteal phase). The experimental protocol will otherwise be the same as in Aims 1 and 2, with participants randomized to either E2 or placebo at the first visit and returning the next month for the other condition.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 12
Model description: Women will participate in one cycle with the estrogen patch and one cycle with the placebo patch. Each cohort will include 40 participants in each of the three study arms for a total of 240 participants.

Arm	Type	Receives
Cohort 1: PTSD Receiving Estradiol then Placebo	Experimental	Drug: Estradiol patch, Other: Placebo patchParticipants with PTSD will record their first cycle with the Clue app. They will receive the estradiol patch during the second cycle, and the placebo patch during the third cycle.
Cohort 1: PTSD Receiving Placebo then Estradiol	Experimental	Drug: Estradiol patch, Other: Placebo patchParticipants with PTSD will record their first cycle with the Clue app. They will receive the placebo patch during the second cycle, and the estradiol patch during the third cycle.
Cohort 1: Trauma without PTSD Receiving Estradiol then Placebo	Active comparator	Drug: Estradiol patch, Other: Placebo patchParticipants with trauma exposure will record their first cycle with the Clue app. They will receive the estradiol patch during the second cycle, and the placebo patch during the third cycle.
Cohort 1: Trauma without PTSD Receiving Placebo then Estradiol	Active comparator	Drug: Estradiol patch, Other: Placebo patchParticipants with trauma exposure will record their first cycle with the Clue app. They will receive the placebo patch during the second cycle, and the estradiol patch during the third cycle.
Cohort 1: Healthy Controls Receiving Estradiol then Placebo	Active comparator	Drug: Estradiol patch, Other: Placebo patchParticipants without trauma history or psychiatric disorder will record their first cycle with the Clue app. They will receive the estradiol patch during the second cycle, and the placebo patch during the third cycle.
Cohort 1: Healthy Controls Receiving Placebo then Estradiol	Active comparator	Drug: Estradiol patch, Other: Placebo patchParticipants without trauma history or psychiatric disorder will will record their first cycle with the Clue app. They will receive the placebo patch during the second cycle, and the estradiol patch during the third cycle.
Cohort 2: PTSD Receiving Estradiol then Placebo	Experimental	Drug: Estradiol patch, Other: Placebo patchParticipants with PTSD will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the estradiol patch before getting the MRI. They will apply the placebo patch during the third cycle.
Cohort 2: PTSD Receiving Placebo then Estradiol	Experimental	Drug: Estradiol patch, Other: Placebo patchParticipants with PTSD will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the placebo patch before getting the MRI. They will apply the estradiol patch during the third cycle.
Cohort 2: Trauma Control Receiving Estradiol, then Placebo	Active comparator	Drug: Estradiol patch, Other: Placebo patchParticipants with trauma exposure will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the estradiol patch before getting the MRI. They will apply the placebo patch during the third cycle.
Cohort 2: Trauma Control Receiving Placebo then Estradiol	Active comparator	Drug: Estradiol patch, Other: Placebo patchParticipants with trauma exposure will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the placebo patch before getting the MRI. They will apply the estradiol patch during the third cycle.
Cohort 2: Healthy Control Receiving Estradiol then Placebo	Active comparator	Drug: Estradiol patch, Other: Placebo patchParticipants without trauma history or psychiatric disorder will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the estradiol patch before getting the MRI. They will apply the placebo patch during the third cycle.
Cohort 2: Healthy Control Receiving Placebo then Estradiol	Active comparator	Drug: Estradiol patch, Other: Placebo patchParticipants without trauma history or psychiatric disorder will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the placebo patch before getting the MRI. They will apply the estradiol patch during the third cycle.

Who may qualify

Ages: 18 to 35 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

African American women
A menstrual period within the past 60 days
Able and willing to give informed consent
Must have a smart phone and willing to install the Clue app

Key exclusion criteria (9 listed)

Women currently taking any form of hormone-based birth control or other hormonal supplement
Women who are pregnant or breastfeeding
Current psychoactive medication use
Nicotine use or smoking
Hypercoagulable conditions

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Estradiol patchEstradiol (E2) patches at a dose of 100ug will be applied 24-48 hours before the MRI scan is performed.	Drug	Cohort 1: Healthy Controls Receiving Estradiol then Placebo, Cohort 1: Healthy Controls Receiving Placebo then Estradiol, Cohort 1: PTSD Receiving Estradiol then Placebo, Cohort 1: PTSD Receiving Placebo then Estradiol, Cohort 1: Trauma without PTSD Receiving Estradiol then Placebo, Cohort 1: Trauma without PTSD Receiving Placebo then Estradiol, Cohort 2: Healthy Control Receiving Estradiol then Placebo, Cohort 2: Healthy Control Receiving Placebo then Estradiol, Cohort 2: PTSD Receiving Estradiol then Placebo, Cohort 2: PTSD Receiving Placebo then Estradiol, Cohort 2: Trauma Control Receiving Estradiol, then Placebo, Cohort 2: Trauma Control Receiving Placebo then Estradiol
Placebo patchPlacebo patch identical to the estradiol patch will be applied 24-48 hours before the MRI scan is performed.	Other	Cohort 1: Healthy Controls Receiving Estradiol then Placebo, Cohort 1: Healthy Controls Receiving Placebo then Estradiol, Cohort 1: PTSD Receiving Estradiol then Placebo, Cohort 1: PTSD Receiving Placebo then Estradiol, Cohort 1: Trauma without PTSD Receiving Estradiol then Placebo, Cohort 1: Trauma without PTSD Receiving Placebo then Estradiol, Cohort 2: Healthy Control Receiving Estradiol then Placebo, Cohort 2: Healthy Control Receiving Placebo then Estradiol, Cohort 2: PTSD Receiving Estradiol then Placebo, Cohort 2: PTSD Receiving Placebo then Estradiol, Cohort 2: Trauma Control Receiving Estradiol, then Placebo, Cohort 2: Trauma Control Receiving Placebo then Estradiol

Primary outcome

Amygdala Response to Fearful Faces Stimuli
Time frame: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)
Responses to threat cues are assessed by functional magnetic resonance imaging (fMRI) responses as participants view 15 blocks each of fearful face and neutral face stimuli, while amygdala reactivity is measured. The amygdala is separated in the right and left hemispheres, and subdivided into the basolateral amygdala and central amygdala. Across voxels in each region a contrast estimate of Fearful > Neutral faces was extracted. The contrast estimate is a standard reporting format for task-based fMRI data, and reflects the magnitude of blood oxygen level dependent (BOLD) activation difference between two experimental conditions. Contrast estimates are an arbitrary, unitless comparison of fMRI BOLD signal units of one experimental condition versus another (threat vs. neutral stimuli). Higher values indicate greater amygdala reactivity to threat cues (vs. neutral cues), a PTSD-linked response pattern. Negative values indicate stronger amygdala reactivity to neutral cues than threat cues.
Amygdala Response to Fear Conditioning Task
Time frame: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)
Indicators of fear conditioning are assessed by fMRI during the fear conditioning tasks. Deficits in fear inhibition have been present in persons with PTSD and during phases of the ovarian cycle. The amygdala is subdivided into the basolateral amygdala and central amygdala. Across voxels in each region a contrast estimate of conditioned stimulation (CS)+ (conditioned threat cues) > CS- (conditioned safety cues) was extracted. The contrast estimate reflects the magnitude of BOLD activation difference between two experimental conditions. Contrast estimates are an arbitrary, unitless comparison of fMRI BOLD signal units of one experimental condition versus another. Positive values indicate strong responsivity to conditioned threats, which could indicate either fear- or memory-related responses. Strong positive values indicate high responsivity to the conditioned threat (CS+), a pattern often associated with PTSD. Negative values indicate greater responsivity to safety cues (CS-).
Ventromedial Prefrontal Cortex (vmPFC) Activation During the Fear Extinction Task
Time frame: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)
Indicators of fear extinction are assessed by fMRI during the fear extinction tasks. Fear extinction is impaired in persons with PTSD and depends on the vmPFC and its inhibition of amygdala responses to threat stimuli. The vmPFC region is defined using the anatomical boundaries of Brodmann area 25 (BA25). Across voxels in this region, a mean contrast estimate of CS+ > CS- in late extinction was extracted. The contrast estimate reflects the magnitude of BOLD activation difference between experimental conditions. Contrast estimates are a unitless comparison of fMRI BOLD signal units of one experimental condition versus another. These values indicate responsivity to conditioned threats. For the vmPFC, a positive value often indicates regulation of emotion or fear now that the threat cues have been extinguished. Strong positive values indicate higher engagement of this region to the conditioned threat (CS+). Negative values indicate higher engagement of this region to safety cues (CS-).

2 secondary outcomes

PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (PCL-5)
Time frame: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)
Beck Depression Inventory (BDI)
Time frame: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)

Results and safety

Results posted to the registry on 22 Jul 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: PTSD Receiving Estradiol Then Placebo	15	14
Cohort 1: PTSD Receiving Placebo Then Estradiol	7	7
Cohort 1: Trauma Without PTSD Receiving Estradiol Then Placebo	10	10
Cohort 1: Trauma Without PTSD Receiving Placebo Then Estradiol	14	14
Cohort 1: Healthy Controls Receiving Estradiol Then Placebo	10	9
Cohort 1: Healthy Controls Receiving Placebo Then Estradiol	12	11
Cohort 2: PTSD Receiving Estradiol Then Placebo	9	8
Cohort 2: PTSD Receiving Placebo Then Estradiol	10	8
Cohort 2: Trauma Control Receiving Estradiol, Then Placebo	12	10
Cohort 2: Trauma Control Receiving Placebo Then Estradiol	10	6
Cohort 2: Healthy Control Receiving Estradiol Then Placebo	7	7
Cohort 2: Healthy Control Receiving Placebo Then Estradiol	11	11

Primary outcome: Amygdala Response to Fearful Faces Stimuli

Time frame: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days). Mean (Standard Deviation). Unit: arbitrary units

Measure	Cohort 1: PTSD Receiving Estradiol n = 19	Cohort 1: PTSD Receiving Placebo n = 17	Cohort 1: Trauma Control Receiving Estradiol n = 21	Cohort 1: Trauma Control Receiving Placebo n = 21	Cohort 1: Healthy Controls Receiving Estradiol n = 18	Cohort 1: Healthy Controls Receiving Placebo n = 19	Cohort 2: PTSD Receiving Estradiol n = 12	Cohort 2: PTSD Receiving Placebo n = 14	Cohort 2: Trauma Control Receiving Estradiol n = 16	Cohort 2: Trauma Control Receiving Placebo n = 15	Cohort 2: Healthy Control Receiving Estradiol n = 17	Cohort 2: Healthy Control Receiving Placebo n = 15
Early-cycle: Left basolateral amygdala	0.03 (0.15)	0.00 (0.11)	0.03 (.012)	0.06 (0.11)	-0.01 (0.07)	0.01 (0.14)	–	–	–	–	–	–
Early-cycle: Right basolateral amygdala	0.00 (0.13)	0.04 (0.11)	0.03 (.013)	0.05 (.011)	-0.00 (0.09)	0.05 (0.14)	–	–	–	–	–	–
Early-cycle: Left central amygdala	0.05 (0.17)	0.00 (0.15)	0.02 (0.17)	0.00 (0.15)	0.05 (0.19)	0.04 (0.23)	–	–	–	–	–	–
Early-cycle: Right central amygdala	0.05 (0.14)	0.06 (0.15)	0.08 (0.15)	0.09 (0.14)	0.01 (0.16)	0.01 (0.18)	–	–	–	–	–	–
Mid-cycle: Left basolateral amygdala	–	–	–	–	–	–	0.07 (0.14)	0.02 (0.09)	0.09 (.013)	0.02 (0.11)	0.04 (0.10)	0.06 (0.10)
Mid-cycle: Right basolateral amygdala	–	–	–	–	–	–	0.09 (0.12)	0.06 (0.11)	0.07 (0.13)	-0.04 (0.16)	0.00 (0.07)	0.07 (0.12)
Mid-cycle: Left central amygdala	–	–	–	–	–	–	0.03 (0.13)	0.01 (0.13)	0.04 (0.14)	0.03 (0.15)	0.02 (0.13)	0.05 (0.14)
Mid-cycle: Right central amygdala	–	–	–	–	–	–	0.03 (0.17)	0.04 (0.12)	0.08 (0.14)	-0.05 (0.09)	-0.02 (0.16)	0.09 (0.11)

Population analysed: Cohort 1 was examined during the early-cycle, while Cohort 2 was examined mid-cycle.

Primary outcome: Amygdala Response to Fear Conditioning Task

Measure	Cohort 1: PTSD Receiving Estradiol n = 18	Cohort 1: PTSD Receiving Placebo n = 19	Cohort 1: Trauma Control Receiving Estradiol n = 18	Cohort 1: Trauma Control Receiving Placebo n = 17	Cohort 1: Healthy Controls Receiving Estradiol n = 19	Cohort 1: Healthy Controls Receiving Placebo n = 19	Cohort 2: PTSD Receiving Estradiol n = 12	Cohort 2: PTSD Receiving Placebo n = 15	Cohort 2: Trauma Control Receiving Estradiol n = 15	Cohort 2: Trauma Control Receiving Placebo n = 14	Cohort 2: Healthy Control Receiving Estradiol n = 18	Cohort 2: Healthy Control Receiving Placebo n = 16
Early-cycle: Basolateral amygdala	.013 (0.31)	-0.05 (0.53)	-0.03 (0.41)	-0.07 (0.34)	0.06 (0.36)	0.17 (0.29)	–	–	–	–	–	–
Early-cycle: Central amygdala	0.37 (0.33)	0.19 (0.32)	0.08 (0.39)	0.17 (0.37)	0.36 (0.36)	0.37 (0.27)	–	–	–	–	–	–
Mid-cycle: Basolateral amygdala	–	–	–	–	–	–	0.13 (0.44)	0.16 (0.38)	-0.07 (0.47)	-0.13 (0.43)	0.09 (0.43)	0.04 (0.36)
Mid-cycle: Central amygdala	–	–	–	–	–	–	0.30 (0.40)	0.19 (0.32)

Primary outcome: Ventromedial Prefrontal Cortex (vmPFC) Activation During the Fear Extinction Task

Measure	Cohort 1: PTSD Receiving Estradiol n = 16	Cohort 1: PTSD Receiving Placebo n = 18	Cohort 1: Trauma Control Receiving Estradiol n = 19	Cohort 1: Trauma Control Receiving Placebo n = 19	Cohort 1: Healthy Controls Receiving Estradiol n = 16	Cohort 1: Healthy Controls Receiving Placebo n = 17	Cohort 2: PTSD Receiving Estradiol n = 13	Cohort 2: PTSD Receiving Placebo n = 16	Cohort 2: Trauma Control Receiving Estradiol n = 15	Cohort 2: Trauma Control Receiving Placebo n = 12	Cohort 2: Healthy Control Receiving Estradiol n = 16	Cohort 2: Healthy Control Receiving Placebo n = 16
Early cycle	-0.01 (0.07)	-0.02 (0.04)	-0.03 (0.05)	-0.00 (0.05)	0.01 (0.05)	0.00 (0.07)	–	–	–	–	–	–
Mid-cycle	–	–	–	–	–	–	-0.00 (0.06)	0.02 (0.06)	0.02 (0.05)	-0.00 (0.08)	-0.00 (0.03)	-0.00 (0.03)

Population analysed: Cohort 1 was examined during the early-cycle, while Cohort 2 was examined mid-cycle.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Information on adverse events was collected beginning at the time of randomization and continued to 30 days after the final study visit. The longest duration of follow-up for adverse events was 830 days as participants enrolled prior to the Coronavirus Disease 2019 (COVID-19) pandemic were followed during the time that research was suspended until their participation could be completed upon the study resuming.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: PTSD Receiving Estradiol	0 of 21 (0%)	7 of 21 (33.3%)	0 of 21
Cohort 1: PTSD Receiving Placebo	0 of 19 (0%)	3 of 19 (15.8%)	0 of 19
Cohort 1: Trauma Control Receiving Estradiol	0 of 22 (0%)	6 of 22 (27.3%)	0 of 22
Cohort 1: Trauma Control Receiving Placebo	0 of 21 (0%)	4 of 21 (19%)	0 of 21
Cohort 1: Healthy Controls Receiving Estradiol	0 of 20 (0%)	4 of 20 (20%)	0 of 20
Cohort 1: Healthy Controls Receiving Placebo	0 of 21 (0%)	5 of 21 (23.8%)	0 of 21
Cohort 2: PTSD Receiving Estradiol	0 of 14 (0%)	3 of 14 (21.4%)	0 of 14
Cohort 2: PTSD Receiving Placebo	0 of 18 (0%)	7 of 18 (38.9%)	0 of 18
Cohort 2: Trauma Control Receiving Estradiol	0 of 18 (0%)	1 of 18 (5.6%)	0 of 18
Cohort 2: Trauma Control Receiving Placebo	0 of 19 (0%)	0 of 19 (0%)	0 of 19
Cohort 2: Healthy Control Receiving Estradiol	0 of 18 (0%)	2 of 18 (11.1%)	0 of 18
Cohort 2: Healthy Control Receiving Placebo	0 of 16 (0%)	2 of 16 (12.5%)	0 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. There is an agreement with the National Institute of Mental Health (NIMH) to share deidentified data with Research Domain Criteria (RDoC) database (a centralized NIH database). Raw neuroimaging data and behavioral data for the 3 tasks (Fearful Faces, Fear Conditioning, Fear Extinction), T1 structural brain images, non-identifying demographics, PTSD Checklist for DSM-5 (PCL-5), and Beck Depression Inventory (BDI) will be shared.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jennifer Stevens, PhD principal investigator

Emory University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Estradiol patch in people with PTSD and Trauma, run by Emory University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Amygdala Response to Fearful Faces Stimuli (time frame: Early-cycle for Cohort 1 (mean 4.5 (sd=1.5) days following onset of menstrual period) or Mid-cycle for cohort 2 (mean 5.5 (sd=1.4) days following a positive urine luteinizing hormone test) during cycles 2 and 3 (each cycle is an average of 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03973229.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.