Clinical trial NCT05388656: Estrogen Variability and Irritability During the Menopause Transition
Official title: Identifying Neurophysiological Mechanisms of Susceptibility to Estradiol Fluctuation and Irritability Symptoms in the Menopause Transition: An Experimental Approach
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Menopause
Irritable Mood
Keywords: Perimenopause
Menopause transition
Estrogen
Stress
Mood
Irritability
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2022-05-24
Enrollment: 50
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

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®

Primary outcomes:
measure: Mean IDAS Ill Temper Scale Score Over Time
timeFrame: up to Week 13
Secondary outcomes:
measure: Theta Oscillatory Activity (4-8 Hz) In Response To Dot Probe Task (Indexing Threat) Over Time
timeFrame: up to Week 13
measure: Beta Oscillatory Activity (13-30 Hz) In Response To Affective Posner Paradigm (probing Frustration) Over Time
timeFrame: up to Week 13
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Carolina Crossing B, Suite 1
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Susan Girdler, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Elizabeth Andersen, PhD
role: PRINCIPAL_INVESTIGATOR
References: