Phase 4
N=34
Estrogen Variability and Irritability During the Menopause Transition
Menopause · Irritable Mood
Bottom Line
View on ClinicalTrials.gov: NCT05388656 ↗Enrolled (actual)
34
Serious AEs
0.0%
Results posted
Nov 2025
Primary outcome: Primary: Mean IDAS Ill Temper Scale Score Over Time — 6.19; 6.02 score on a scale — p=0.09
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release (Drug); Placebo (Drug); Progesterone 200 mg (Drug)
- Age
- Adult · 45+ yrs
- Sex
- Female
- Sponsor
- University of North Carolina, Chapel Hill
- Primary completion
- Dec 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean IDAS Ill Temper Scale Score Over Time |
6.19; 6.02 | 0.09 |
| SECONDARY Reward Positivity (RewP) in Response to the Affective Posner Paradigm |
-2.59; -2.13 | 0.0018 sig |
| SECONDARY 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. |
2.92; 2.99 | 0.0108 sig |
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.
Eligibility 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®
Data sourced from ClinicalTrials.gov (NCT05388656). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.