Transcriptional and Epigenetic Program of PCOS Women

Inclusion criteria

• Women;
• Age 18-45 years inclusive;
• BMI 23-40 kg/m2 inclusive;
• HbA1C ≤ 6.0% or fasting plasma glucose < 126 mg/dL;
• Weight stable (± 3 kg) during the 3 months prior to enrollment;
• Women must be > 9 months post-partum;
• For PCOS: A documented history of PCOS from their physician according to the Androgen Excess (AE)-PCOS criteria: (defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders (eg. hypoadrenalism, ovarian tumors)
• Regular menstrual cycle for females without PCOS
• Able to provide written, informed consent.

Exclusion criteria

• Postmenopausal women
• Women with hysterectomy
• Pregnancy, lactation or < 9 months postpartum from the scheduled date of screening.
• Fasting plasma glucose > 126 mg/dL, or HbA1c > 6% or diagnosis with Type 2 Diabetes (T2D) or Type 1 Diabetes (T1D)
• History or presence of cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on EKG), presence of cardiac pacemaker, implanted cardiac defibrillator.
• Liver disease (AST or ALT >2.5 times the upper limit of normal)
• Kidney disease (creatinine >1.6 mg/dl or estimated GFR <60 ml/min)
• Dyslipidemia, including triglycerides >500 mg/dl, LDL >200 mg/dl
• Anemia (hemoglobin <11 g/dl)
• Thyroid dysfunction (suppressed thyroid-stimulating hormone, elevated TSH <10 µIU/ml if symptomatic or elevated TSH >10 µIU/ml if asymptomatic)
• Uncontrolled hypertension (BP >160 mmHg systolic or >100 mmHg diastolic)
• Elevated hsCRP or known active infection
• History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable)
• History of drug or alcohol abuse (> 3 drinks per day) within the last 5 years. Current drug use may be determined by plasma or urine drug screens.
• psychiatric disease prohibiting adherence to study protocol.
• History of organ transplant.
• Known history of HIV, active Hepatitis A, B or C or tuberculosis.
• History of bariatric surgery.
• Current smokers (smoking within the past 3 months).
• Current use of beta-adrenergic blocking agents.
• Use of oral or injectable anti-hyperglycemic agents: metformin, sulfonylureas, DPP IV inhibitors, SGLT-2 inhibitors, thiazolidinediones, acarbose, GLP-1 analogs and insulin unless willing to undertake a washout period of 15 days for metformin and GLP-1 analogs and undergo subsequent laboratory screening tests.
• Gonadotropin Releasing Hormone (GnRH) and/or Antiandrogen use within the last 2 months.
• Use of any medications known to influence fat and/or energy metabolism (eg growth hormone therapy, glucocorticoids [steroids], etc.)
• Initiation or change in hormone replacement therapy within the past 3 months (including, but not limited to thyroid hormone, estrogen replacement therapy or In Vitro Fertilization therapy).
• Current treatment with blood thinners or antiplatelet medications that cannot be safely stopped for biopsy and testing procedures.
• Not able or willing to have DXA scans or are above the acceptable weight limit (450 lbs) of the DXA scanner.
• Presence of any condition that, in the opinion of the Investigators, compromises participant safety or data integrity or the participant's ability to complete study visits.
• Not able to participate in MRI assessments due to:

• Metal implants (pacemaker, non-removable body piercings, aneurysm clips) based on Investigator's judgment at screening
• Physical limitations or equipment tolerances (e.g., MRI bore size) based on Investigator's judgment at screening
• Inability to tolerate MRI imaging without sedation or claustrophobia