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NCT05388656

Estrogen Variability and Irritability During the Menopause Transition

Completed Phase 4 Results posted Last updated 26 November 2025
What this trial tests

Phase 4 trial testing Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release in Menopause in 40 participants. Completed in 17 January 2025.

Timeline
15 June 2022
Primary endpoint
17 December 2024
17 January 2025

Quick facts

Lead sponsorUniversity of North Carolina, Chapel Hill
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingquadruple
Primary purposebasic science
Enrollment40
Start date15 June 2022
Primary completion17 December 2024
Estimated completion17 January 2025
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of North Carolina, Chapel Hill

Who can join

Adults 45 to 59, female only, with Menopause or Irritable Mood. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean IDAS Ill Temper Scale Score Over Time Primary · 3 weeks during each intervention

The 5-item ill temper scale of the Inventory of Depression and Anxiety Symptoms (IDAS) will be the primary measure of irritability symptom severity. Each symptom item is rated 1 (not at all) to 5 (extremely). The total IDAS ill temper scale score may range from 5-25. Higher scores indicate more severe irritability symptoms. The average daily irritability scores will be evaluated for each 3-week treatment condition (Active Estradiol vs. Placebo).

GroupValue95% CI
Estradiol6.19± 1.33
Placebo6.02± 1.02
Reward Positivity (RewP) in Response to the Affective Posner Paradigm Secondary · At the end of each three-week treatment period.

Dysfunctional reward construct of irritability was indexed by the Reward Positivity (RewP), an event-related potential (ERP), that occurs 250-350 ms after feedback indicating a reward (e.g., a monetary win) compared to non-reward (e.g., too slow). The difference waveform is extracted from the frontal midline electrode (Fz). The average ERP is reported to represent the amplitude in response to stimulus presentation.

GroupValue95% CI
Estradiol-2.59± 3.19
Placebo-2.13± 3.13
Mean LPP Amplitude During Implicit Viewing Task Dysfunctional Threat Processing Was Indexed by Greater Late Positive Potential (LPP) Component for Emotional Face Stimuli, Elicited 400-900 Milliseconds After the Stimulus Presentation. Secondary · At the end of each 3-week treatment period

Implicit Viewing Task: Participants will complete the Implicit Viewing Task while EEG is recorded to examine brain responses (late positive potentials (LPP) to anger stimuli. During the task, participants will be presented with a happy, fear or calm faces and the participant is asked to indicate whether the image shows someone with long or short hair (neutral feature, not emotion related). LPP will be extracted from the midline-parietal electrode (Pz), from 400-900 ms after the stimulus presentation. The average LPP amplitude will be assessed at the end of each 3-week treatment period. Additio

GroupValue95% CI
Estradiol2.92± 1.62
Placebo2.99± 1.49

Adverse events — posted to ClinicalTrials.gov

Time frame: From the time of the first laboratory visit through final follow up visit, up to approximately 3 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Estradiol
Serious: 0/33 (0%)
Deaths: 0/33
Placebo
Serious: 0/31 (0%)
Deaths: 0/31
Progesterone
Serious: 0/31 (0%)
Deaths: 0/31
Other adverse events (17 terms — click to expand)

ReactionSystemEstradiolPlaceboProgesterone
Non-migrainous headache (no visual symptoms)Nervous system disorders
Pain in legsVascular disorders
Increased nausea and breast tendernessReproductive system and breast disorders
Irritation at patch siteSkin and subcutaneous tissue disorders
Prolonged bleedingReproductive system and breast disorders
Migraine headache without auraNervous system disorders
Pain in right calf and swelling in legsVascular disorders
Swelling in legsVascular disorders
Increased breast tendernessReproductive system and breast disorders
Concerning breast lumpsReproductive system and breast disorders
RashSkin and subcutaneous tissue disorders
Swollen LipsSkin and subcutaneous tissue disorders
"Bump" on vulvaReproductive system and breast disorders
Intermittent chest painCardiac disorders
Numbness in fingertipsVascular disorders
Swelling in left ankleVascular disorders
Changes in vision/trouble with contactsEye disorders

Data from ClinicalTrials.gov NCT05388656 adverse events section.

Sponsor's own description

Women in the menopause transition (perimenopause) experience substantial day-to-day variability in estradiol and have a 2-4-fold increase in major depression risk. About 40% of perimenopausal women are susceptible to the emergence of affective symptoms tied to changes in estradiol. Among the perimenopausal women with affective impairment, most report irritability, not "depression," is their primary source of impairment and distress. The purpose of this research is to determine the neurophysiologic basis of susceptibility to estradiol fluctuations and irritability symptoms in perimenopausal women.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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Other recruiting trials for Menopause

Currently open trials in the same condition.

Other University of North Carolina, Chapel Hill trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT05388656.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing