University of North Carolina, Chapel Hill
This proposal will examine the effects of estradiol administration on perimenopausal-onset (PO) anhedonia and psychosis symptoms as well as on brain function using simultaneous positron emission tomography and functional magnetic resonance imaging (PET-MR).
The transition to menopause (the "perimenopause") is characterized by increased risk for new onset of depression and psychosis. Our work and that of others has demonstrated that a prominent symptom of perimenopausal-onset (PO) depression is anhedonia, contributing significantly to distress and functional impairment. Additionally, the incidence of psychosis in women may increase during this period. Declining or low levels of estradiol, particularly in the late perimenopause, may play a role in the pathogenesis of PO anhedonia and PO psychosis via effects on mesolimbic brain reward circuitry and…
Inclusion Criteria: * Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures, lifestyle considerations, and availability for the duration of the study * 44-55 years old unmedicated perimenopausal women who have ≥ 2 skipped menstrual cycles, amenorrhea ≥ 60 days, corresponding to the late menopause transition (Stages of Reproductive Aging Workshop (STRAW stage -1). * Anhedonia or psychosis symptoms that began during the period of menstrual irregularity. * Clinician's Global Impression Scale-Severity score (CGI-S) \> 3 to confirm a clinicall…
Participants will be randomized to receive transdermal estradiol (100μg/day) patch for 3 weeks.
Participants will receive an additional week of micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation.
Participants will be randomized to receive a transdermal estradiol-matching placebo patch for 3 weeks
All Participants will receive two PET-MR scans using \[11C\]raclopride IV as the tracer. The first scan will occur at baseline and the second at post treatment after 3 weeks.
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