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.

• MRI Visit (Device), also known as magnetic resonance imaging: MRI visit will take approximately 1.5 hour (55-60 minutes in MRI) and will involve structural scans of the brain, and scans at rest and while performing cognitive tasks.
• Laboratory Visit (Other): DEXA scan for obtaining body composition, NIH toolbox to assess cognitive test, and optional graded exercise test (GXT).

Primary outcomes

• Cerebral Blood Flow (CBF) at rest [data collected during a 2-hour MRI visit (anytime up to 3 months on study)]: Arterial Spin Labeling (ASL) color atlases and 4D Flow MRI will be used to measure CBF at rest. CBF will be measured in each of six brain regions: temporal, parietal, frontal, occipital, subcortical, and brainstem.
• Circulating Sex Hormone Levels [data collected during a 2-hour MRI visit (anytime up to 3 months on study)]

Secondary outcomes

• Body composition via DEXA scan [data collected during a 2-hour lab visit (anytime up to 3 months on study)]: Percent body fat and lean mass to be measured via Dual-Energy X-ray Absorptiometry (DEXA) scan.
• NIH Toolbox: Dimensional Change Card Sort Test [data collected during a 2-hour lab visit (anytime up to 3 months on study)]: NIH Toolbox to assess neurocognitive function. The Dimensional Change Card Sort Test measures accuracy: the number of accurate responses, up to a maximum of 40.
• NIH Toolbox: Pattern Comparison Processing Speed Test [data collected during a 2-hour lab visit (anytime up to 3 months on study)]: NIH Toolbox to assess neurocognitive function. The Pattern Comparison Processing Speed Test measures how many correct responses the participant has within 90 seconds. There is a maximum of 130 items.
• NIH Toolbox: Flanker Inhibitory Control and Attention [data collected during a 2-hour lab visit (anytime up to 3 months on study)]: NIH Toolbox to assess neurocognitive function. The Flanker test is a measure of executive function and is scored using a T-score where 100 is the average, higher scores indicate better performance.
• Cardiorespiratory fitness (VO2max) [Optional] [data collected during a 2-hour lab visit (anytime up to 3 months on study)]

Sex: Female, ages: 18 Years to 45 Years, accepts healthy volunteers

Inclusion Criteria (Participants with PCOS):

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

  1. Presence of clinical hyperandrogenism or biochemical hyperandrogenism
  2. A history of irregular menstrual cycles
  3. 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

• Laura Cooney, MD, Principal investigator, University of Wisconsin, Madison