Elsevier

Contraception

Volume 80, Issue 1, July 2009, Pages 18-24
Contraception

Original research article
Efficacy and safety of a low-dose combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20 mcg in a 24/4-day regimen

https://doi.org/10.1016/j.contraception.2009.01.016Get rights and content

Abstract

Objective

The study was conducted to assess the efficacy of a low-dose combined oral contraceptive (COC) containing drospirenone (drsp) 3 mg/ethinylestradiol (EE) 20 mcg administered for 24 days of active treatment followed by a 4-day hormone-free interval (24/4 regimen).

Study Design

In this open-label uncontrolled study conducted in 50 European centers, healthy females aged 18–35 years with a body mass index of less than 30 kg/m2 received drsp 3 mg/EE 20 mcg 24/4 over 13 cycles. The primary efficacy variable was the number of unintended pregnancies.

Results

Five pregnancies occurred among 1101 women over 13,248 treatment cycles, resulting in a Pearl Index (PI) of 0.49 with an upper two-sided 95% CI limit of 1.14. Of these pregnancies, three were attributed to noncompliance with tablet use resulting in an adjusted PI for ‘perfect use’ of 0.22 (upper limit of two-sided 95% CI: 0.80) based on 11,755 cycles.

Conclusion

Drospirenone 3 mg/EE 20 mcg 24/4 is a highly effective COC in nonobese women.

Introduction

Combined oral contraceptives (COCs) are an effective form of reversible contraception [1], [2], with an estimated overall failure rate of 0.3% assuming perfect use [2]. Since they were first introduced in the early 1960s, the continued development of COCs has focused mainly on reducing the dose of estrogen and introducing new progestogens with favorable clinical profiles in order to improve safety and tolerability without adversely affecting contraceptive efficacy.

Drospirenone (drsp), a spirolactone analogue, is the newest progestogen available for use in gynecological preparations and has pharmacological properties that are similar to those of endogenous progesterone [3], [4]. Drsp has both antimineralocorticoid and antiandrogenic activity, in addition to its potent progestogenic activity [3], [4], [5]. The antimineralocorticoid activity of drsp counteracts the aldosterone-stimulating mineralocorticoid effect of estrogen, thereby reducing the retention of water and sodium caused by ethinylestradiol (EE). In addition, the antiandrogenic activity of drsp enables it to suppress androgen-mediated disorders of the skin such as acne, seborrhea and hirsutism.

Clinical studies with a low-dose COC comprising drsp 3 mg/EE 30 mcg in a conventional 21/7-day regimen (Yasmin®; Bayer Schering Pharma, Berlin, Germany) have shown it to be an extremely effective contraceptive that is associated with good cycle control and an acceptable safety profile [6], [7], [8], [9]. In addition, drsp 3 mg/EE 30 mcg was associated with an improvement in preexisting acne and seborrhea [8], an improvement in fluid retention and its associated symptoms [9], [10], [11], [12] and a positive effect on physical premenstrual symptoms [10], [13], [14].

A low-dose COC comprising drsp 3 mg/EE 20 mcg in a 24/4-day regimen was subsequently developed and is licensed for use in a number of countries worldwide. In clinical trials to date, this formulation has been shown to have reliable contraceptive efficacy, a favorable bleeding pattern and a good safety profile [15], [16]. In addition, it has been clinically proven to significantly alleviate the emotional and physical symptoms associated with premenstrual dysphoric disorder (PMDD) that are severe enough to affect patient's daily lives [17], [18]. Furthermore, drsp 3 mg/EE 20 mcg in a 24/4-day regimen has been shown to have proven benefits in the treatment of acne [19].

In the current study, we assessed the efficacy, safety and user satisfaction associated with drsp 3 mg/EE 20 mcg in a 24/4-day regimen in nonobese women in Europe.

Section snippets

Study design

This was an open-label, Phase III study performed at 50 centers in Europe (Czech Republic, Italy, Hungary, Slovak Republic, Latvia and Belgium) between March 2004 and January 2006. The study was conducted in accordance with the Declaration of Helsinki and was subject to national laws and approval by local ethics committees. All women provided written inform consent prior to entry into the study.

Inclusion and exclusion criteria

The study enrolled healthy female volunteers who were at risk of pregnancy (sexually active) and who

Results

A total of 1129 women were screened and 1113 of these were recruited into the study (Fig. 1). Treatment was initiated in 1101 women, who comprised the FAS. Of those recruited, 961 (86.4%) women completed all 13 treatment cycles.

The demographic and baseline characteristics of the FAS are shown in Table 1. All but one of the women were Caucasian, and the vast majority (99%) had had sexual relations and/or were sexually active at screening. Most women (73.8%) had never given birth, and 86.0% had

Discussion

The results of this study indicate that a COC comprising drsp 3 mg/EE 20 mcg in a 24/4-day regimen has good contraceptive efficacy and is associated with an acceptable safety profile in nonobese women in Europe. In addition, drsp 3 mg/EE 20 mcg was associated with a high rate of user satisfaction and with an improvement in emotional and physical well-being.

The unadjusted PI reported in the current study was 0.49, which is comparable to those reported in other clinical trials of drsp/EE [7], [8]

Acknowledgments

The authors would like to thank Raewyn Poole and Lyndal McMillan for editorial assistance during the preparation of the manuscript.

References (34)

Cited by (26)

  • Bioequivalence study of an oral contraceptive containing ethinylestradiol/drospirenone/levomefolate calcium relative to ethinylestradiol/drospirenone and to levomefolate calcium alone

    2012, Contraception
    Citation Excerpt :

    The first 24 days of the planned 28-day cycle pack provide once daily tablets containing EE 0.02 mg/drsp 3 mg/levomefolate calcium 0.451 mg, followed by a 4-day period with once-daily tablets containing levomefolate calcium 0.451 mg only. The preparation combines the established profile of EE 0.02 mg/drsp 3 mg, including contraceptive efficacy [24,25], treatment of moderate acne [26–29] and the treatment of the emotional and physical symptoms associated with premenstrual dysphoric disorder [30,31], with an improved folate status. Changing formulations and administering several agents concomitantly may, potentially, affect the pharmacokinetics of the active ingredients, and therefore, it is important to demonstrate bioequivalence for all active ingredients.

  • Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: A randomized, double-blind, active-controlled, parallel-group, US-based multicenter study

    2012, Contraception
    Citation Excerpt :

    Overall, EE 20 mcg/drsp 3 mg/levomefolate calcium 0.451 mg was well tolerated with a similar safety profile to EE 20 mcg/drsp 3 mg. Discontinuation due to AEs was 3.7%, slightly lower than that observed in other studies of EE 20 mcg/drsp 3 mg (range 5.9%–7.5% of women) [39–42]. In conclusion, EE 20 mcg/drsp 3 mg/levomefolate calcium 0.451 mg provides clinically beneficial increases in folate status and decreases in homocysteine levels and is well tolerated compared with EE 20 mcg/drsp 3 mg alone in a US population of healthy women requesting contraception.

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This study was supported by an unrestricted grant from Bayer Schering Pharma AG, Berlin, Germany.

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