Examining the Effects of Estradiol on Neural and Molecular Response to Reward

This study investigates whether estradiol (a form of estrogen) given via skin patch can improve mood and reduce depression-like symptoms (particularly loss of pleasure, called anhedonia) in women going through the transition to menopause. Brain scans and blood tests are used to understand how estrogen affects the brain's reward system. **You may be eligible if...** - You are a woman aged 44–55 in the late menopausal transition (you've missed at least 2 periods or had no period for 60+ days) - You are not currently on any psychiatric medications or hormone therapy - You have symptoms of anhedonia (loss of pleasure or motivation) or mild psychosis that started during your menstrual changes - Your symptoms are clinically significant enough to impact daily life **You may NOT be eligible if...** - You have a history of breast or ovarian cancer, or carry the BRCA1/2 gene mutation - You have had psychiatric illness before menopause started (prior to the current episode) - You have heart, liver, or kidney disease - You have a peanut allergy or cannot have MRI scans (e.g., metal implants) - You are currently using psychotropic medications, hormones, or anti-inflammatory drugs frequently Talk to your doctor to see if this trial is right for you.