Elsevier

Contraception

Volume 81, Issue 3, March 2010, Pages 209-214
Contraception

Original research article
Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study

https://doi.org/10.1016/j.contraception.2009.09.011Get rights and content

Abstract

Background

This study was conducted to compare the effects of the combined contraceptive vaginal ring releasing 15 mcg of ethinylestradiol (EE) and 120 mcg of etonorgestrel daily with the effects of the contraceptive patch, a transdermal system that delivers a daily dose of 20 mcg of EE and 150 mcg of norelgestromin on bone turnover and bone mineral density (BMD) in young fertile women.

Study Design

On the basis of a randomized, computer-generated list, 40 women desiring contraception were assigned to a 12-month treatment with a patch delivering a daily dose of 20 mcg of EE and 150 mcg of norelgestromin (Evra®, Janssen-Cilag, Italy) (Group A, n=20) or to a 12-month treatment with a vaginal ring releasing a daily dose of 15 mcg of EE and 120 mcg of etonorgestrel (NuvaRing®, Organon, Italy) (Group B, n=20). Twenty patients underwent no treatment and were used as healthy controls (Group C, n=20). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin and urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) levels were measured. At baseline and after 12 months, lumbar BMD was determined by dual-energy X-ray absorptiometry.

Results

In Groups A and B, urinary PYD and D-PYD at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C values (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Group A and Group B in urinary levels of PYD and D-PYD, in calcium levels and in osteocalcin levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values.

Conclusion

Both contraceptive systems exert a similar positive influence on bone turnover in young postadolescent women.

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.

References (25)

  • FleischerK. et al.

    Effects of the contraceptive patch, the vaginal ring and an oral contraceptive on APC resistance and SHBG: a cross-over study

    Thromb Res

    (2008)
  • RoumenF.J.

    Review of the combined contraceptive vaginal ring, NuvaRing®

    Ther Clin Risk Manag

    (2008)
  • Cited by (36)

    • Eating Disorders in Children and Adolescents: A Practical Review and Update for Pediatric Gynecologists

      2021, Journal of Pediatric and Adolescent Gynecology
      Citation Excerpt :

      COCs that contain greater than 30 μg of ethinyl estradiol (EE) seem to have a more favorable effect on bone accretion and should be preferred to EE pills with a lower dosage.67-70 The contraceptive patch and vaginal ring are effective methods of contraception that do not seem to negatively affect BMD.71-73 Depot medroxyprogesterone acetate is an effective contraceptive method but leads to decreased BMD in teens and should be used cautiously in malnourished patients.74,75

    • Bones and Birth Control in Adolescent Girls

      2020, Journal of Pediatric and Adolescent Gynecology
    • Intrauterine devices and other forms of contraception: Thinking outside the pack

      2015, Medical Clinics of North America
      Citation Excerpt :

      It was first marketed in 2002 and overall effectiveness was not significantly different for the patch versus COCs, but compliance seemed to be better than COCs in 3 trials.38 The transdermal delivery approach minimizes the peaks and troughs of hormone concentrations associated with daily oral administration and avoids hepatic first-pass metabolism.40 Patch users noted more side effects of breast discomfort, dysmenorrhea, nausea, and vomiting than with COCs.38

    • Menstrual Suppression in the Adolescent

      2013, Journal of Pediatric and Adolescent Gynecology
      Citation Excerpt :

      Studies on combined oral contraceptives and bone density have reported variable results, with no consensus on the ideal ethinyl estradiol dose for bone health.59 Similarly, investigations into the transdermal patch's effect on bone health have yielded inconsistent results with findings in adults more reassuring than in adolescents.60–62 The limited investigation of bone health with the vaginal ring points to its bone neutrality, but these studies have not included adolescents younger than 18 years.60,61

    View all citing articles on Scopus
    View full text