PCOS and Brain Health

Aim 1: To determine whether individuals with PCOS exhibit reduced CBF at global, lobe and regional brain levels.

Aim 2: To assess whether individuals with PCOS have alterations in brain structure including grey and white volume, cortical thickness, or connectivity compared to controls.

Aim 3: To evaluate whether individuals with PCOS demonstrate impairments in cognitive performance, including verbal fluency, memory, and processing speed, relative to controls.

Aim 4: To characterize systemic immune cell states, circulating inflammatory and metabolic profiles, and epigenomic regulatory landscapes in peripheral blood of individuals with and without PCOS, and to evaluate whether these multiomic signatures are associated with CBF, brain structure, connectivity, and cognitive performance.

Inclusion criteria

(Participants with PCOS):

• Rotterdam criteria demonstrating two out of the three criteria. These are:

• Presence of clinical hyperandrogenism or biochemical hyperandrogenism
• A history of irregular menstrual cycles
• Presence of polycystic ovarian morphology on ultrasound

Inclusion criteria

(Healthy Controls):

• Regular menstrual cycles (not meeting criteria for irregular cycles above)
• No diagnosis of PCOS
• Controls may have isolated hirsutism or polycystic ovaries on ultrasound as long as they do not meet Rotterdam criteria for PCOS

Exclusion criteria

• Current pregnancy
• Preexisting diagnosis of type 1 diabetes
• Severe obesity (body mass index (BMI) greater than 45kg/m2)
• Preexisting diagnosis of hypertension requiring antihypertensive medication or blood pressure of greater than 160/100 on two separate occasions during clinical care
• History of neurologic disease or stroke
• History of myocardial infarction or deep venous thrombosis
• Endometriosis confirmed by prior laparoscopy
• Autoimmune conditions including lupus, multiple sclerosis, and active malignancy
• Immuno-modulating medications
• Conditions incompatible with MRI scanning, including but not limited to

• Certain implanted metal devices or foreign bodies
• Severe claustrophobia
• Post-menopausal
• Participants will be excluded if they have taken hormonal contraception or fertility medication in the last month