Estrogen Variability and Irritability During the Menopause Transition

What this trial studies

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.

Conditions in scope

• Menopause
• Irritable Mood

Interventions

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

Who can join

Women only · Ages 45 Years to 59 Years · Accepts healthy volunteers.

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

Eligibility wording paraphrased from the public record. View the full criteria on ClinicalTrials.gov before contacting a site.

Where it’s happening

Status & timeline

• Overall status: Completed
• Study type: Interventional
• Phase: PHASE4
• Start date: 2022-06-15
• Primary completion: 2024-12-17
• Last update posted: 2025-11-26
• First posted: 2022-05-24

Sponsor & contact

Lead sponsor: University of North Carolina, Chapel Hill (Other)

Collaborators: National Institute of Mental Health (NIMH)

For trial site contact information, use the official record at ClinicalTrials.gov. Contact details change frequently and the public record is the source of truth.

Outcome measures

Primary outcomes

• Mean IDAS Ill Temper Scale Score Over Time (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…

Related ClearedRx care

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