Original research articleEffects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study
Introduction
In the last few years, two new combined contraceptive formulations have been introduced: the transdermal patch (Evra®, Janssen-Cilag, Italy) and the vaginal ring (NuvaRing®, Organon, Italy). The rationale of their development was to provide administration alternatives for the combined oral contraceptive (COC) and to improve convenience and thus compliance. These two new formulations are designed to deliver a low daily dose of hormones to the systemic circulation [1].
The contraceptive patch is a 20-cm2 transdermal system that delivers a daily dose of 150 mcg of norelgestromin (NGMN) and 20 mcg of ethinylestradiol (EE) for 7 days. It is replaced on the same day for three consecutive weeks. The fourth week is “patch free”, inducing withdrawal bleeding. Each contraceptive patch contains a total drug content of 6.0 mg of NGMN and 0.75 mg of EE and consists of a thin matrix-type system with three layers. The backing layer is composed of a translucent, flexible polyester film, upon which is the middle drug-adhesive layer that contains the active components EE and NGMN. The release liner or third layer is composed of a clear polyester film that protects the adhesive layer during storage and is removed just before application. In clinical trials, the contraceptive patch has demonstrated the same safety and efficacy of OCs, and results indicated that women who use the patch do so more correctly and consistently than those who use OCs. The enhanced patient compliance may be due to the once-a-week dosing and relative ease of use of this system. The transdermal delivery approach minimizes the “peaks and troughs” of hormone concentrations associated with daily oral administration and avoids hepatic first-pass metabolism [2].
The combined contraceptive vaginal ring (NuvaRing®) is a once-a-month method of hormonal contraception. It consists of a flexible, soft and transparent ring measuring 54 mm in diameter and 4 mm in thickness that can easily be inserted by the woman herself into her vagina. After 3 weeks of use, the patient removes the ring, thereby introducing a ring-free week, during which withdrawal bleeding normally occurs. The ring is made of the copolymer evatane, in which the hormones EE (2.7 mg) and etonorgestrel (ENG) (11.7 mg) are equally dispersed. ENG is 3-ketodesogestrel, which is the active metabolite of the progestin desogestrel. Due to the composition of the ring, it steadily releases 15 mcg of EE and 120 mcg of ENG daily, which are then continuously absorbed through the vaginal epithelium. Vaginal administration of contraceptive hormones with NuvaRing® has the advantage of avoiding gastrointestinal absorption and hepatic first-pass metabolism [3].
Many clinical and experimental studies have focused on the effect exerted by OCs on the skeleton and on identifying the minimal estrogen dose necessary for maintaining such beneficial actions on the bone [4], [5], [6].
In our previous studies, we evaluated the effects of OCs with decreasing doses of EE [5], [7] and different types of progestins [8] on bone turnover and bone mineral density (BMD) and our results have shown a similar positive effect of these formulations on bone turnover without any significant modification of BMD during 1 year of treatment in young postadolescent women.
In this study, we evaluated the effects of the transdermal patch and the vaginal ring on bone turnover and BMD in young and healthy fertile women.
Section snippets
Materials and methods
From May to October 2008, all women referring to the family planning clinic of our department were asked to participate in a study on the effects of transdermal and vaginal administration of contraceptives on bone metabolism and BMD.
The purpose of the protocol was clearly explained to the patients before they entered the study; written informed consent was obtained from all women enrolled. All the procedures performed were in accordance with the guidelines of the Helsinki Declaration on human
Results
Among the 60 women selected for the study, 49 completed the study. In Group A, 1 patient discontinued the treatment for personal reasons, 2 discontinued it for skin reaction to the patch (not clinically evident) and 1 discontinued it for irregular bleeding. In Group B, 2 patients discontinued the treatment for personal reasons and 2 others discontinued it for irregular bleeding. In Group C, 1 patient was excluded for becoming pregnant and 2 were excluded for missing the follow-up visit after 3
Discussion
COC use has been associated with increased cortical and trabecular bone mass and higher BMD in both premenopausal and postmenopausal women in some studies [12], [13], [14], [15], [16], [17]. However, other studies did not find a positive effect of COCs on bone mass [18], [19], [20], [21], [22]. No study has ever suggested an adverse effect on bone in adult women.
In a previous study [5], [6], [7], [8], we investigated the influence of COCs containing different doses of EE and different types of
Acknowledgment
This study was supported by the institutional funds of our department.
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