Eligible participants and measured variables: We will enroll healthy, reproductive-age females (18-45 years) for this pharmacogenomic study. We will exclude females with contraindications to the use of estrogen-containing contraception based on the CDC Medical Eligibility Criteria (MEC) guidelines for any conditions with a category 3 or 4 recommendations26. We will also exclude females who have used an injectable contraceptive method (e.g., depot medroxyprogesterone acetate) within the last 6 months or currently using an ENG contraceptive implant. Females currently using a COCP will qualify for enrollment into the study after completing a 7-day washout from their current COCP formulation. As a 7-day washout or placebo period is standard for routine use of COCPs, there are no risks to potential participants currently using a COCP to undergo a 7-day washout period. The study team will coordinate with the participant’s clinical care provider in order to inform them that their patient’s COCP formulation may be changing from the one that was clinically prescribed and to ensure that the patient does not have any contraindications that would exclude them from taking the DSG/EE pill. All participants will complete the informed consent process, including signing the consent form, prior to conducting any 7-day washout from a clinically prescribed COCP formulation or a 4-week washout from a clinically prescribed CYP3A inducer/inhibitor

Who can Participate

In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Female, aged 18-45 years old 4. In good general health as evidenced by medical history and no need for regular intensive medical interventions (e.g., inpatient admissions, surgical treatments). The Principal Investigator will be responsible for determining good general health for potential participants with complicated medical histories. 5. Ability to take oral medication and be willing to adhere to the oral contraceptive pill (DSG/EE) regimen 6. Interested in taking or are currently taking a clinically prescribed COCP for the prevention of pregnancy 7. Body-mass index ≥18.5kg/m2 8. Willing to abstain from medications and supplements known to induce/inhibit CYP3A (e.g., rifampin, carbamazepine, ketoconazole, St. John’s wort) during the study 9. Normal blood pressure measurement at study screening 10. Negative urine pregnancy test at study screening In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Female, aged 18-45 years old 4. In good general health as evidenced by medical history and no need for regular intensive medical interventions (e.g., inpatient admissions, surgical treatments). The Principal Investigator will be responsible for determining good general health for potential participants with complicated medical histories. 5. Ability to take oral medication and be willing to adhere to the oral contraceptive pill (DSG/EE) regimen 6. Interested in taking or are currently taking a clinically prescribed COCP for the prevention of pregnancy 7. Body-mass index ≥18.5kg/m2 8. Willing to abstain from medications and supplements known to induce/inhibit CYP3A (e.g., rifampin, carbamazepine, ketoconazole, St. John’s wort) during the study 9. Normal blood pressure measurement at study screening 10. Negative urine pregnancy test at study screening An individual who meets any of the following criteria will be excluded from participation in this study: 1. Currently taking any known CYP3A inducers/inhibitors (e.g., rifampin, carbamazepine, ketoconazole, St. John’s wort)43 2. Any medical conditions that affect liver function (e.g., hepatitis, cirrhosis) 3. Individuals who are currently taking a clinically prescribed COCP formulation for the primary indication of treatment of conditions other than prevention of pregnancy 4. Contraindications to estrogen-containing contraception (based on category 3 or 4 recommendations in the CDC MEC guidelines42) a. Current breast cancer or personal history of breast cancer b. Severe decompensated cirrhosis c. Personal history of deep venous thrombosis or pulmonary embolism d. Recent major surgery with prolonged immobilization e. Diabetes with nephropathy, retinopathy, neuropathy, or other vascular disease f. Current gallbladder disease g. Migraine headaches with aura h. History of malabsorptive bariatric surgery i. History of cholestasis due to past oral contraceptive pill use j. Personal history of hypertension k. Personal history of ischemic heart disease l. Known thrombogenic mutations m. Personal history of focal nodular hyperplasia of the liver, hepatocellular adenoma, or malignant hepatoma n. Multiple sclerosis with prolonged immobility o. History of peripartum cardiomyopathy p. Current tobacco smoker and age ≥35 years q. History of complicated solid organ transplantation r. Personal history of stroke s. Personal history of superficial venous thrombosis t. Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies u. Complicated valvular heart disease v. Current use of fosamprenavir or lamotrigine 5. Use of injectable contraceptive method within 6 months or current use of an ENG implant 6. Childbirth within 6 months

Study ID