Feasibility Study Into the Contraceptive Effect of Estetrol

Inclusion Criteria:

• At least 18 years and not older than 40 years of age
• Willing to use a barrier method of contraception during the wash-out cycle, the pre-treatment cycle, the period of study drug administration, the period of lynestrenol intake (if applicable), and 14 days thereafter or until the follow-up visit if this 14-days period ends before the follow-up visit.
• Women who ovulate in the pre-treatment cycle before or on day 24 (±1) after start of their menses, who have a subsequent P concentration of > 16 nmol/l and whose next menstruation does not start within 6 days after ovulation
• Body Mass Index > 18 and <30 kg/m2
• Good physical and mental health
• Both ovaries visible upon ultrasonography
• Willing to give informed consent in writing

Exclusion Criteria:

• Clinically significant abnormal results of routine hematology, serum biochemistry, urinanalysis, and/or ECG in the opinion of the Investigator at screening.
• Known or suspected pregnancy
• Lactation
• Pregnancy during accurate hormonal contraceptive use
• Known or suspected breast cancer or a history of breast cancer
• Clinically significant abnormalities of the uterus and/or ovaries detected by examination and/or ultrasound (non-physiological ovarian mass or significant uterine pathology).
• A cervical smear with clinically relevant abnormal cytology within one year before study start.
• Previous use of depot progestogen preparations in the last 6 months.

• Contraindications for contraceptive steroids:

  • a history of, or existing thromboembolic, cardiovascular or cerebrovascular disorder
  • a history of, or existing conditions predisposing to, or being prodromi of, a thrombosis
  • a known defect in the blood coagulation system (e.g. deficiencies in AT-III, protein C, S, and APC resistance)
  • heterozygous for a mutation in coagulation factor II and/or positive for factor V Leiden
  • the presence of a severe or more than one risk factor for vascular disease (e.g. dyslipoproteinaemia; diabetes mellitus; hyperhomocysteinaemia; systemic lupus erythematosus; chronic inflammatory bowel disease; antiphospholipid antibodies; smoking; venous thromboembolism in sibling or parent below the age of 50, or arterial disease in sibling or parent below the age of 35; within 2 weeks after full remobilisation following surgery)
  • hypertension, i.e. systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg
  • disturbance of liver function: e.g. cholestatic jaundice, a history of jaundice of pregnancy or jaundice due to previous oestrogen use, Rotor syndrome and Dubin-Johnson syndrome
  • known or suspected hormone-dependent tumours or endometrial hyperplasia
  • undiagnosed vaginal bleeding
  • porphyria
  • a history during pregnancy or previous hormone-use of severe pruritus, herpes gestationis or deterioration of otosclerosis

• Use of one or more of the following medications:

  • sex steroids other than the medication of study
  • use at present or within 2 months before start study medication:
  • hydantoins, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, troglitazone, felbamate, rifampicin, rifabutin, griseofulvin and St. John's wort (Hypericum perforatum)
• Status post-partum or post-abortion within a period of 2 months before study start
• Administration of investigational drugs within 3 months before start study medication
• A history of (within 12 months) alcohol or drug abuse
• A known hypersensitivity for one of the components of the study medication (eg arachisoil and lactosis)