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 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®