WISE Study

Women’s Irritability, Stress, and Estrogen Study

UNC WISE Study logo: pink lotus on a purple background above the words "UNC WISE Study" Complete an online screening to find out if you are eligible!

Help us learn about the role of estrogen on mood during the menopause transition!

Women in the menopause transition (perimenopause) have a significantly greater risk of developing depression. For most women with depressive symptoms during the menopause transition, irritability not “depression” is their primary source of impairment and distress. While most women are exposed to erratic hormone changes in the menopause transition, about 40% are susceptible to the emergence of mood symptoms tied to changes in estrogen. Estrogen modulates brain systems associated with depression; has anti-depressant/anti-anxiety effects; and regulates brain networks involved in depression. Thus, the purpose of this study is to understand the biological mechanisms underlying the relationship between estrogen and the emergence of irritability symptoms during the menopause transition.

What is the study all about?

Women in the menopause transition (meaning women who have irregular or skipped menstrual periods but have not gone a full year without a menstrual period) are more likely to suffer from depression and anxiety not only compared with men but also compared with women who still have regular menstrual periods (premenopausal women) and women who have not had a menstrual period in more than one year (postmenopausal women). The menopause transition is a time of extreme changes in sex hormone levels. One of the main female sex hormones is estrogen. Estrogen levels can change greatly from one day to the next during the menopause transition. In other research, changes in sex hormone levels have been shown to contribute to negative mood in women with severe premenstrual syndrome (PMS) and in women with postpartum depression. Estrogen has also been shown to influence brain areas that are important in the emergence of mood symptoms, including irritability. Although the causes of depression during the menopause transition are unknown, severe life stress close in time to the menopause transition predicts the onset of depression.

The purpose of this research study is to determine if changes in estrogen (specifically a urinary metabolite of estrogen, E1G) during the menopause transition are related to irritability symptoms and brain correlates of irritability. We will also test whether administering estrogen for three weeks via a skin patch, will decrease irritability symptoms and beneficially modify brain activity associated with irritability symptoms.

Who is eligible?

Women ages 45-59 who are medically healthy in the menopause transition (having irregular or skipped periods) and are currently experiencing mood changes, particularly irritability.

What does participation involve?

Baseline Hormone, Mood and Neurophysiological Testing (4 weeks):

Screening questionnaire to determine eligibility (5 min)
Clinical interview and enrollment session (interview and questionnaires on mood, stress, and personal medical and psychiatric history, and menopausal symptoms (1 hr)
Daily and weekly mood assessments
Every-other-day hormone collections (urine)
Neurophysiological testing session: In-person laboratory session involving non-invasive measurement of brain activity (EEG) during a computer task (~1 hour).

Condition 1: Estradiol or Placebo Patch (3 weeks):

Daily and weekly mood assessments
Neurophysiological testing session (~1 hour).

Washout Phase – no patches (3 weeks):

Daily and weekly mood assessments

Condition 2: Estradiol or Placebo Patch (3 weeks):

Daily and weekly mood assessments
Neurophysiological testing session (~1 hour).

End of Study and Follow-up (3 weeks):

10 days of progesterone to protect your uterine lining.
Daily and weekly mood assessments

Compensation

Participants have the chance to earn up to $650 for completing the entire research study.