Effects of Transdermal Estradiol on Brain Reward Response in Perimenopausal Women with Anhedonia and Psychosis

What this Trial Is About

Researchers are studying the effects of estradiol on symptoms of anhedonia and psychosis that begin during perimenopause, the transition to menopause. The study aims to understand how estradiol influences brain function and dopamine activity in reward processing using combined PET and fMRI brain imaging. This research focuses on women experiencing these symptoms during late perimenopause and explores the role of declining estradiol levels in these conditions. Participants will be randomly assigned to receive either a transdermal estradiol patch 100 mcgday for three weeks followed by one week of combined estradiol and micronized progesterone 200 mgday or a matching placebo patch for three weeks. The study uses a double-blind, placebo-controlled design with groups balanced by severity of anhedonia and psychosis symptoms. All participants will have two PET-MR scans using 11Craclopride to measure dopamine function and brain responses to reward before and after treatment. Throughout the study, participants will complete clinical assessments of anhedonia and psychosis symptoms, including scales like the Snaith-Hamilton Pleasure Scale and the Brief Psychiatric Rating Scale. Brain imaging with PET-MR will track changes in striatal activation and dopamine release during reward tasks. The primary outcome is the change in striatal activation during a monetary incentive delay task from baseline to study endpoint. Safety and adherence to the estradiol regimen will be monitored during the approximately seven-week study period.

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