Original research articleEfficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial
Introduction
Combined oral contraceptives (COCs) provide effective and safe protection against pregnancy and are the method of choice for many women worldwide. However, COCs are associated with a number of disadvantages including exposure to hepatic first-pass metabolism, susceptibility to reduced uptake because of vomiting or food interactions and fluctuations in serum hormone levels resulting from daily pill administration [1], [2], [3]. Additionally, women regard the need for daily pill intake as a drawback to the use of oral contraceptives (OCs) [4].
These observations illustrated the need for alternative methods of hormonal contraception and led to the development of vaginal rings to administer contraceptive steroids. A combined contraceptive vaginal ring (NuvaRing, NV Organon, Oss, The Netherlands) that delivers 15 μg of ethinylestradiol (EE) and 120 μg of etonogestrel (ENG) per day over 3 consecutive weeks has been developed.
NuvaRing has several advantages over OCs. It is the only self-administered contraceptive that can be taken once monthly and features a controlled-release design that results in more uniform contraceptive hormone concentrations throughout the day, thus avoiding the daily fluctuations associated with OCs. Also, the vaginal route of administration avoids hepatic first-pass metabolism and gastrointestinal interference, allowing lower doses of contraceptive hormones to be used [1]. Peak serum concentrations of EE and ENG are achieved approximately 1 week after insertion of the ring and are 60−70% lower than peak concentrations produced by a COC containing 150 μg of desogestrel and 30 μg of EE [1].
Tolerability is a major factor in determining the acceptability of a contraceptive method. The contraceptive efficacy, tolerability and safety of NuvaRing have been described in large-scale studies conducted in Europe and North America [5], [6], indicating that it is an effective and safe contraceptive method. NuvaRing is also perceived as a convenient contraceptive method with a high level of user and partner acceptability [4], [5], [6].
In small-scale studies over six treatment cycles, NuvaRing has been shown to produce superior cycle control and to have comparable tolerability with a COC delivering daily EE and levonorgestrel (LNG) at 30 and 150 μg, respectively [7]. To date, the efficacy and tolerability of NuvaRing have not been compared with those of a COC in a large, randomized study. With this in mind, we conducted a 1-year, randomized controlled trial to compare NuvaRing with a COC delivering 30 μg of EE and 150 μg of LNG daily by assessing cycle control, contraceptive efficacy, tolerability and treatment compliance. The primary objective of this trial was to compare the cycle control of NuvaRing with that of the COC; these data will be presented in full elsewhere. In this paper, we describe the contraceptive efficacy, tolerability and safety of and compliance with the two contraceptive regimens.
Section snippets
Materials and methods
This Phase III, open-label, randomized, group-comparative, multicenter trial was conducted in 11 countries in Europe and South America (Belgium, Brazil, Chile, Denmark, Finland, France, Germany, Italy, Norway, Spain and Sweden). The study was approved by the independent ethics committee/institutional review boards of the participating centers and was conducted in accordance with the Declaration of Helsinki and the ICH Guideline for Good Clinical Practice. All subjects provided written informed
Subject disposition
A total of 1079 subjects was randomized for treatment. Of these, 49 women discontinued prior to treatment, 9 (NuvaRing, n=6; COC, n=3) withdrew as they were pregnant at baseline, 3 (NuvaRing, n=3) were lost to follow-up, 15 (NuvaRing, n=7; COC, n=8) were unwilling to cooperate with the study protocol and 22 (NuvaRing, n=13; COC, n=9) discontinued due to other reasons.
Of the randomized subjects, 1030 received treatment (NuvaRing, n=512; COC, n=518) and comprised the intent-to-treat (ITT)
Discussion
This Phase III, open-label, randomized, group-comparative, multicenter trial demonstrated that NuvaRing is as effective and well tolerated as a commonly used COC.
The efficacy, tolerability and acceptability of NuvaRing have been well established [5], [6] and its cycle control and tolerability have been shown to be comparable with those of a COC over six contraceptive cycles [7]. Our study is the first 1-year, open-label, randomized controlled trial to directly compare the efficacy and safety of
Acknowledgments
This study was supported by NV Organon, Oss, The Netherlands. T. Dieben and C. Verhoeven are employees of NV Organon.
The authors would like to thank and acknowledge the participation of the following investigators during this trial: A. Saey, U. Gaspard, M. Renier (Belgium); N.R. de Melo, M. Poli, E. Coutinho, E.A.J. Pellini, R. Pereira de Andrade, L. Bahamondes, M.E.H.D. Yazzle, M.A. Albernaz, J. Sabino Pinho Neto, C.E. Fernandes (Brazil); J.C. Montero (Chile); P. Hein, F. Ahlstrøm, K. Rubeck
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