Clinical Research Directory

Inclusion Criteria: * Female sex assigned at birth; * Age 18-40 years; * Premenopausal status characterized by regular (i.e., 21-35 day cycles) menstrual cycles or a follicle stimulating hormone (FSH) \< 10 IU/L in patients with irregular menstrual cycles. * Body mass index \< 39 kg/m2. Exclusion Criteria: * Preexisting or active cardiac, renal, or hepatic disease or use of medications for these disorders: past or current history of these diseases or conditions may impact participant safety associated with the intervention or may confound the study of the effect of the interventions because these diseases also impair vascular function. * Current use or use of hormonal contraceptives within past 3 months. * Use of vascular-altering medications that interfere with measurements (e.g., anti-hypertensive medications, GLP-1s, acetazolamide, etc.,). * Diabetic or fasted glucose ≥126 mg/dL: diabetes impairs vascular function and could influence interpretation of the data. * Current or recent (\<6 months) tobacco or nicotine use. * Pregnant, planning to become pregnant or breastfeeding within the past 3 months. * Known contraindications to MRI such as metal shavings or fragments in the head, eyes or neck. * Rested seated blood pressure \>140/90 mmHg; hypertension impairs cerebrovascular function and could influence the interpretation of data. * Use of vitamins, supplements or minerals or anti-inflammatory medications or unwillingness to stop for 7 days prior to MRI testing. * Abnormal thyroid, liver, or kidney function testing during the screening examination or bloodwork. Abnormal kidney function defined as creatinine \>1.3mg/dL. Abnormal liver function tests within 1.5x ULN. UCH Clinical Lab ULN for AST and ALT are 39 and 52, respectively. Individuals with TSH levels outside of the normal range (0.5-5.0 mIU/mL) will be referred to their PCP and will be allowed study entry once their TSH levels are normalized \> 2 months; * Current medical insurance; for safety. Additional drug related exclusion criteria: We will additionally exclude for the following reasons as related to safety or contraindications for study medications: * Known hypersensitivity to study medications. * Suicidal ideation or suicidal behavior as evaluated using the C-SSRS * Use of medications contraindicated for the study medications (e.g., organic anion transporting polypeptide (OATP) 1B1, CYP3A inhibitors, or rifampin. * Total cholesterol \> 220 mg/dL at screening. * History of venous thromboembolic events (VTE), known inherited or acquired hypercoagulopathies; thrombogenic valvular or thrombogenic rhythm diseases of the heart (e.g., atrial fibrillation). * History of breast cancer or other estrogen-dependent neoplasm. * Osteoporosis defined as bone mineral density T-score ≤ -2.0. * Headaches with focal neurological symptoms or have migraine headaches with aura if over the age of 35 years. * Undiagnosed uterine bleeding.