NCT05388656

Estrogen Variability and Irritability During the Menopause Transition

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

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: University of North Carolina, Chapel Hill · Academic / Other
• Sex: Female
• Age: 45 Years – 59 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

Using a within-subjects, cross-over design and transdermal estradiol to stabilize estradiol fluctuations (and increase levels) the investigators will test if neural dynamics (oscillatory activity in the theta and beta frequencies assessed via EEG) associated with key constructs of irritability (attentional bias to threat and frustration to non-reward) represent a biomarker target of irritability symptom response to transdermal estradiol.

Conditions

• Menopause
• Irritable Mood

Interventions

Type	Name	Description
DRUG	Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release	0.1 mg/day transdermal patch administered for 3 weeks
DRUG	Placebo	Estradiol-matched placebo patch administered for 3 weeks
DRUG	Progesterone 200 mg	200 mg tablet administered by mouth once per day for 10 days after completion of the experimental phase of the study

Timeline

• Start date: 2022-06-15
• Primary completion: 2024-12-17
• Completion: 2025-01-17
• First posted: 2022-05-24
• Last updated: 2025-11-26
• Results posted: 2025-11-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study