ABSTRACT
BACKGROUND: This trial was conducted to compare cycle control with vaginal ring a combined contraceptive vaginal ring, and a combined oral contraceptive (COC) delivering 30 mug ethinylestradiol (EE) and 150 mug levonorgestrel. METHODS: This open-label, randomized, multi-centre, Phase III study involved adult women from 11 countries. Subjects were treated with either vaginal ring or a COC for 13 cycles (12 months). RESULTS: A total of 1030 subjects (vaginal ring, n=512; COC, n=518) comprised the intention-to-treat (ITT) population. The percentage of women in the ITT population who completed the trial was 70.9% for vaginal ring and 71.2% for the COC group. The incidence of breakthrough bleeding and spotting over cycles 2-13, the primary efficacy parameter, was lower with vaginal ring (range 2.0-6.4%) than the COC (range 3.5-12.6%), and for cycles 2 and 9 the lower incidence with vaginal ring was confirmed as statistically significant (P=0.003 and P=0.002 respectively). The incidence of intended bleeding was significantly higher over all cycles with vaginal ring (58.8-72.8%) than with the COC (43.4-57.9%). CONCLUSIONS: Cycle control with vaginal ring was excellent and superior to that of a COC containing 30 mug EE.
Subject(s)
Contraceptive Devices, Female , Contraceptives, Oral, Synthetic/administration & dosage , Estrogens/administration & dosage , Ethinyl Estradiol/administration & dosage , Levonorgestrel/administration & dosage , Adult , Contraceptive Devices, Female/adverse effects , Contraceptives, Oral, Synthetic/adverse effects , Estrogens/adverse effects , Ethinyl Estradiol/adverse effects , Female , Humans , Incidence , Levonorgestrel/adverse effects , Menstrual Cycle/drug effects , Patient Compliance , Pregnancy , Pregnancy Rate , Uterine Hemorrhage/epidemiologyABSTRACT
OBJECTIVES: To compare carbohydrate metabolism, adrenal and thyroid function during use of a combined contraceptive vaginal ring (NuvaRing, NV Organon, Oss, The Netherlands) with those of a combined oral contraceptive. METHODS: Healthy women aged 18-40 years used either the vaginal ring, delivering 15 microg ethinylestradiol and 120 microg of etonogestrel per day, or a combined oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel, for six cycles. Each cycle comprised 3 weeks of use of the ring or the pill followed by 1 ring- or pill-free week. The following parameters were measured at baseline and at the end of cycles 3 and 6: carbohydrate metabolism (glucose, insulin, glycosylated hemoglobin); adrenal function (total cortisol, cortisol binding globulin, dehydroepiandrosterone sulfate); thyroid function (thyroid stimulating hormone, free thyroxine). RESULTS: Small and similar increases in insulin were seen in both groups. Concentrations of cortisol binding globulin and total cortisol rose significantly less during ring use than during combined oral contraceptive use (cycle 3, p= 0.0002; cycle 6, p < 0.0001). Levels of dehydroepiandrosterone sulfate did not change in either group. Thyroid stimulating hormone levels increased significantly more in the ring group at cycle 3 (p = 0.0016) but free thyroxine levels were unchanged in both groups. CONCLUSIONS: Both the vaginal ring and the oral contraceptive have no clinically relevant effects on carbohydrate metabolism, adrenal or thyroid function.
Subject(s)
Blood Glucose/drug effects , Contraceptive Devices, Female , Contraceptives, Oral, Combined/pharmacology , Ethinyl Estradiol/pharmacology , Levonorgestrel/pharmacology , Adolescent , Adrenal Glands/drug effects , Adult , Blood Glucose/metabolism , Carrier Proteins/blood , Carrier Proteins/drug effects , Contraceptives, Oral, Combined/administration & dosage , Dehydroepiandrosterone Sulfate/blood , Drug Administration Schedule , England , Ethinyl Estradiol/administration & dosage , Female , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Humans , Hydrocortisone/blood , Insulin/blood , Levonorgestrel/administration & dosage , Netherlands , Scotland , Thyroid Gland/drug effects , Thyrotropin/blood , Thyrotropin/drug effects , Thyroxine/blood , Thyroxine/drug effects , Treatment OutcomeABSTRACT
A new guideline on the clinical investigation of steroid contraceptives in women, which has been released by the European Agency for the Evaluation of Medicinal Products (EMEA), calls for the calculation of a confidence interval for the Pearl Index, a widely used measure to describe the effectiveness of a contraceptive method. However, the interpretation of the Pearl Index as a statistical parameter, for which a confidence interval can be calculated, needs further clarification. The guideline does not provide the necessary definitions. In this paper, two statistical models, the Bernoulli model and the Poisson model, are compared; both can be used for the calculation of the Pearl Index and its upper confidence limit. The Poisson model proved to be more suitable, because it can accommodate incomplete treatment cycles. Unambiguous definitions and statistical formulae for the calculation of overall Pearl Index and the Method Failure Pearl Index are given. Finally, the sample sizes required to fulfill the EMEA's guideline are given.
