Estrogen Variability and Irritability During the Menopause Transition

Inclusion Criteria:

• Healthy women 45 - 59 years of age

• In the early menopause transition (defined by variable menstrual cycle length thatis 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 (otherthan 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 forbreast, 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 oilused in Prometrium®