An open-label, randomized, parallel group trial in healthy female subjects to compare the pharmacokinetics of ethinyl estradiol (EE) of NuvaRing®, a contraceptive patch (EVRA(TM)) and an oral contraceptive (Microgynon® 30).

Inclusion Criteria:

• Subject is at least 18 but not older than 40 years of age on Day 1 of treatment.
• Subject has uterus and ovaria in situ
• Subject who does not use hormonal contraception and is willing to use adequate nonhormonal contraceptive measures during the timeframe between screening and start treatment.
• Subject is able and willing to refrain from caffeine and/or xanthine containing food and/or beverages (e.g. coffee, tea, cola or chocolate) from 24 hours before the first administration of the trial medication until the last PK blood sample.
• Subject is willing not to consume grapefruit containing products 14 days prior to the start of the first administration of the trial medication until the last PK blood sample.
• Subject is willing to refrain from smoking from 7 days prior to first administration of the trial medication until the last pharmacokinetic blood sample.
• Subject is willing to refrain from alcohol containing products from 24 hours prior to first administration of the trial medication until the last pharmacokinetic blood sample.

Exclusion Criteria:

• Contraindications for use of NuvaRing, contraceptive patch and oral contraceptive:
• Presence or history of venous thrombosis, with or without the involvement of pulmonary embolism.
• Presence or history of arterial thrombosis (e.g. cerebrovascular accident, myocardial infarction) or prodromi of a thrombosis (e.g. angina pectoris or transient ischaemic attack).
• Known predisposition for venous or arterial thrombosis, with or without hereditary involvement such as Activated Protein C (APC) resistance, antithrombin-III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant) and Factor V Leiden mutation.
• Diabetes mellitus with vascular involvement
• The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis (to be judged by the (sub-) investigator
• Presence or history of severe hepatic disease as long as liver function values had not returned to normal or were judged to be clinically significant by the investigator.
• Presence or history of liver tumours (benign or malignant).
• Known or suspected malignant conditions of the genital organs or the breasts, if sex-steroid-influenced.
• Undiagnosed vaginal bleeding.
• Hypersensitivity to the active substances or to any of the excipients of NuvaRing, contraceptive patch and oral contraceptive.
• Migraine with focal aura
• Known or suspected pregnancy
• Breastfeeding, or within 2 months after stopping breastfeeding on the day preceding the first administration of trial medication (Day -1).
• Clinically significant abnormal laboratory, ECG (electrocardiogram) vital signs, physical and gynecological findings at screening.
• A significant (history of) allergic or other serious disease, particularly gastrointestinal tract disease.
• Smoking more than 5 cigarettes or 1 pipe or 1 cigar per day for a period of at least 3 months prior to screening.
• Using any systemic medication (including over the counter (OTC) medication) during the 14 days prior to the day preceding the first administration of trial medication (Day -1), except for oral contraceptive used for synchronization and occasional Ibuprofen.
• Used any drug or substance that is known to induce drug-metabolizing enzymes within two months prior to the start of synchronization.
• Received a contraceptive by injection, an implant or hormonal intra-uterine device within 6 months of the day preceding the first administration of trial medication (Day -1), or a hormonal implant or hormonal intra-uterine device removed within 6 months of the day preceding the first administration of trial medication (Day -1).
• Participated in a drug trial and was administered an investigational drug during the 90 days prior to start of synchronization.
• Donated blood during the 90 days prior to the day preceding the first administration of trial medication (Day -1).
• History (within the last 2 years) of excessive alcohol use, use of solvents or of drug abuse.
• Positive drug test at screening and/or admission (Day -1), or a positive alcohol test at admission (Day -1).
• Clinically significant abnormal cervical smear result (papaninecolaou (PAP) III or higher) at screening.
• Acute or chronic hepatitis B/C or human immune deficiency virus (HIV) 1&2 infection.