Pharmacokinetics and Pharmacodynamics of 3 Dosages of Estriol After Continuous Vaginal Administration for 21 Days

Inclusion Criteria: * Body-mass index (BMI) ≥18.5 kg/m² and ≤ 30.0 kg/m² * Postmenopausal state: FSH (plasma) ≥ 40 IU/l, estradiol (serum) ≤ 20 pg/ml last spontaneous menstruation at least 12 months ago * Normal transvaginal endometrial scan (endometrial thickness \< 5 mm) * Good state of health * Non-smoker or ex-smoker for at least 6 month * Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial Exclusion Criteria: * Existing cardiac, hepatic and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability and/or pharmacokinetics and/or pharmacodynamics of the active ingredient * History of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders * Known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations * Subjects with severe allergies or multiple drug allergies, unless it is judged as not relevant for the clinical trial by the investigator * Positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test (if positive to be verified by test for HBc-IgM) or anti-HCV-test * Presence or history of venous or arterial thrombosis (e.g. deep venous thrombosis, pulmonary embolism) * Known, past or suspected breast cancer or increased familiar risk for development * Known or suspected estrogen-dependent malignant tumours (e.g. endometrial or breast cancer) * Undiagnosed genital bleeding * Acute vaginal infection or other diseases prohibiting the placement of vaginal ring * History of endometrial hyperplasia * Migraine or frequent episodes of severe headache * History of or current drug or alcohol dependence * Subjects who are on a diet which could affect the pharmacokinetics of the active ingredient * Regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day * Blood donation or other blood loss of more than 400 ml within the last 3 months prior to individual enrolment of the subject * Participation in a clinical trial during the last 6 months prior to individual enrolment of the subject * Concomitant systemic therapy with antibiotics, which might interfere with enterohepatic recirculation (e.g. cephalosporines, neomycin, ampicillin or tetracyclines) * Use of sex hormones within 6 months (oral, transdermal, vaginal) or 8 months (intramuscular administered depot preparations used once per month) or 12 months (intramuscular administered depot preparations used once per 3 months) before screening * Use of systemic or topical medications or substances which oppose the study objectives or which might influence them within 8 weeks before screening examination * Subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial