Investigating estrogen's role in irritability during menopause transition

Identifying Neurophysiological Mechanisms of Susceptibility to Estradiol Fluctuation and Irritability Symptoms in the Menopause Transition: An Experimental Approach

Phase 4 Interventional University of North Carolina, Chapel Hill · NCT05388656

This study is testing if using a skin patch with estrogen can help reduce irritability in women going through menopause by looking at changes in their brain activity.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment50 (estimated)
Ages45 Years to 59 Years
SexFemale
SponsorUniversity of North Carolina, Chapel Hill Academic / other
Locations1 site (Chapel Hill, North Carolina)
Trial IDNCT05388656 on ClinicalTrials.gov

What this trial studies

This research focuses on women experiencing the menopause transition, specifically those with increased irritability linked to fluctuating estradiol levels. The study employs a within-subjects, cross-over design using transdermal estradiol to stabilize hormone levels and assess its effects on neural dynamics related to irritability. By measuring oscillatory brain activity through EEG, the study aims to identify biomarkers that correlate with symptom response to estradiol treatment. The goal is to better understand the neurophysiological mechanisms underlying irritability in perimenopausal women.

Who should consider this trial

Good fit: Ideal candidates are healthy women aged 45-59 in the early menopause transition with moderate to severe irritability symptoms.

Not a fit: Patients with a history of severe psychological disorders or those currently on mood-affecting medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options for managing irritability in perimenopausal women.

How similar studies have performed: Other studies have shown promise in understanding hormonal influences on mood, but this specific approach is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Healthy women 45 - 59 years of age
* In the early menopause transition (defined by variable menstrual cycle length that is 7+ days longer or shorter than usual)
* Increase in irritability since the onset of menstrual cycle changes
* Moderate to severe irritability symptoms, as defined by IDAS ill-temper scale score \>10
* Have experienced 1+ very stressful life event (e.g. divorce, death of family member) within the past 6 months
* Negative mammogram within the past two years
* BMI between 18 - 45 kg/m\^2

Exclusion Criteria:

* Use of psychotropic agents or hormonal preparations, or herbal supplements (other than multivitamins) believed to affect mood or menopausal symptoms
* History of psychosis, bipolar disorder, or substance dependence
* Active psychological symptoms severe enough to require treatment
* Current suicidal intent or recent history of suicide attempts (within past 10 years)
* Personal or family history of cancer indicative of more than average risk for breast, ovarian or endometrial cancers
* Personal history of any cardiovascular disease including coronary artery disease, arteriosclerosis, heart attack, stroke
* Personal history of thromboembolic disorders
* History of E2-dependent neoplasia
* History of gallbladder disease
* Recent history of migraine with aura
* Blood pressure classified as higher than stage 2 hypertension (≥160 mmHg systolic or ≥100 mmHg diastolic)
* Liver dysfunction or disease
* Undiagnosed abnormal genital bleeding
* Type I diabetes
* Known sensitivities to the matrix patch system in Climara® or allergy to peanut oil used in Prometrium®

Where this trial is running

Chapel Hill, North Carolina

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions MenopauseIrritable MoodPerimenopauseMenopause transitionEstrogenStressMoodIrritability
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.