The Interaction Between Diabetes and Estradiol on Human Brain Metabolism in Postmenopausal Women

Epidemiological studies suggest there may be an interaction between type 2 diabetes and
estrogen in postmenopausal women, such that diabetes may interact with estrogen levels over
time to increase risk for dementia. The mechanism for this effect is now known. However,
animal research suggests that it may occur through estrogen's effects on cellular metabolism
of glucose and ketone bodies. The primary aim of this study is to test whether type 2
diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be
accomplished by imaging brain metabolism using positron emission tomography before and after
short-term administration of transdermal 17β-estradiol in 10 postmenopausal women with
diabetes and 10 non-diabetic postmenopausal women.

Inclusion Criteria:

1. Willing to provide written informed consent

2. Stated willingness to comply with all study procedures and availability for the
duration of the study

3. Female, postmenopausal, aged 65-80

4. Normal results on recommended healthcare screenings (e.g., mammogram, pap smear,
colonoscopy)

5. BMI 20-30 kg/m2

6. No evidence of dementia or mild cognitive impairment (MoCA score >25)

7. Able to access reliable transportation to study and intervention visits

Exclusion Criteria:

1. Use of hormone replacement therapy within the past 3 months

2. History of renal, heart, liver, or neurological disease; head injury with loss of
consciousness in the past 5 years; chronic pain, anxiety or depression

3. Presence of medical conditions that might contraindicate estrogen use (e.g.,
unexplained vaginal bleeding, history of reproductive tissue cancer, thrombosis)

4. Currently taking insulin, metformin, or any other drug or medication judged by the
study physician to affect safety or research outcomes of interest

5. Involved in another research study

6. Contraindications for MRI or PET scanning

7. Current smoker