Inclusion Criteria:

• Willing and able to give signed informed consent
• No evidence of Coronavirus Disease 2019 (COVID-19) infection based on Centers for Disease Control and Prevention (CDC) testing and/or screening procedures
• Healthy woman, 18 to 40 years of age
• Body mass index (BMI) ≥ 18 kg/m² and < 30 kg/m²
• Willing to refrain from use of alcohol and grapefruit juice from 48 hours prior until completion of the follow-up period
• In good general health, confirmed by medical history, physical examination, and laboratory testing
• Willing to not use other hormonal contraception including oral contraceptive, TDS, or vaginal ring, for the treatment and follow-up period

Exclusion Criteria:

• Known or suspected pregnancy

• Breast-feeding or within 1 month after stopping breast-feeding

• User of injectable contraceptives (e.g., depot-medroxyprogesterone acetate) and less than 3 months since last injection

• User of progestin intrauterine device (IUD) and less than 3 months since last IUD insertion

• Recent pregnancy (within 2 months), including vaginal or cesarean delivery, surgical or medically induced abortion, spontaneous abortion, or ectopic pregnancy

• Unexplained vaginal bleeding

• Undiagnosed abnormal genital bleeding

• Diagnosis of sickle cell

• Known hypersensitivity to, or intolerance of, progestins or estrogens (leading to discontinuation), including hormonal contraception; or history of serious or severe adverse event (SAE) related to progestins or estrogens, including hormonal contraception (e.g., worsening of a disease or condition while on hormonal contraception)

• History of dermal hypersensitivity in response to medicated TDSs (e.g., nicotine TDS) or topical applications (bandages, surgical tape, etc.); known hypersensitivity to any components of the Twirla®, or prior difficulties with transdermal methods for any indication

• Presence on the lower abdomen of skin changes that, at the discretion of the Investigator, would have potentially interfered with TDS adhesion or TDS application site assessment, including for example tattoos, striae, scarring or other skin damage, skin lesions, skin irritation, diffuse skin disease (e.g., psoriasis, eczema, rash, or any etiology), excessive stretch marks, or excess hair at the TDS application site

• Preclusion of TDS placement, at the discretion of the Investigator, on the lower abdomen

• Has a contraindication to combined estrogen-progestin contraceptive use (as defined by a category 3 or 4 condition of the 2016 U.S. Medical Eligibility Criteria for Contraceptive Use), including:

  • Personal history of or DVT or venous thromboembolism
  • History of stroke, vascular or cerebral vascular disease including TIAs or coronary artery disease
  • Known inherited or acquired hypercoagulopathy, including thrombogenic mutations (e.g., factor V Leiden; prothrombin mutation; protein S, protein C, or antithrombin deficiency)
  • Systemic Lupus Erythematosus with positive or unknown antiphospholipid antibodies
  • Known or suspected carcinoma of the breast, including past personal history of breast cancer
  • Jaundice with prior CHC use
  • Hepatocellular adenoma or carcinoma
  • Severe cirrhosis
  • Symptomatic current gallbladder disease
  • Current smokers 35 years of age or over, or smoker who would have turned 35 years old during the course of the trial (Smoking includes cigarettes, cigars, smokeless tobacco, e-cigarettes, hookah, etc.)
  • Headaches with focal neurological symptoms (i.e., migraines with auras)
  • Migraines of any type in women over 35 years of age
  • Diabetes mellitus with nephropathy, neuropathy, retinopathy, or other vascular disease; diabetes mellitus of ˃20 year's duration
  • Elevated blood pressure, defined as screening sitting blood pressure ≥ 140 mm Hg systolic or ≥ 90 mm Hg diastolic; or hypertension with known vascular disease
  • History of peripartum cardiomyopathy

• Known thrombophilia, including antiphospholipid antibody syndrome

• History of any other condition that in the Investigator's opinion suggests an elevated risk of arterial or venous thromboembolic disease

• Carcinoma of the endometrium, ovary, fallopian tubes, or other known or suspected estrogen-dependent malignant or pre-malignant neoplasia

• Other active malignancy, excluding non-melanoma skin cancer

• Known history of acute or chronic hepatocellular disease with a history of significantly abnormal liver function, or liver function tests (LFTs) ≥ 2x normal

• Known history of Triglycerides ≥ 350 mg/dL

• Thrombogenic valvular or thrombogenic rhythm diseases of the heart (e.g., subacute bacterial endocarditis with valvular disease or atrial fibrillation).

• Uncontrolled diabetes mellitus; participants with a history of gestational diabetes are eligible for the study if they are currently euglycemic

• Uncontrolled thyroid disorder

• Known HIV and/or hepatitis B or C infection

• History of suicidal ideation or attempt, or history of severe depression requiring hospitalization within the past year

• Recent history (within prior 12 months) of drug or alcohol abuse or at Investigator discretion, history greater than 12 months prior and at risk for noncompliance

• Positive urine drug screen for Cocaine, Methamphetamine, Opiates, Phencyclidine unless there is a documented prescription with supporting medical history and diagnosis

• Administration of any investigational drug and/or experimental device within 30 days prior to enrollment; planned administration of an experimental drug or device during the duration of the study; current participation in any investigational studies

• In the Investigator's judgement, woman was unsuitable for participation in the study or who could not comply with study procedures

• Participant was a dependent of (e.g., relative or family member) and/or was a member of the Investigator's staff.