Contraceptive efficacy and safety of estradiol valerate/dienogest in a healthy female population: a multicenter, open-label, uncontrolled Phase III study

Qi Yu, Zirong Huang, Mulan Ren, Qing Chang, Zhongqi Zhang, Susanne Parke, Qi Yu, Zirong Huang, Mulan Ren, Qing Chang, Zhongqi Zhang, Susanne Parke

Abstract

Background: To investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women.

Methods: In this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study.

Results: A total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG.

Conclusion: EV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population.

Clinical trials registry: ClinicalTrials.gov identifier: NCT01638910.

Keywords: Asian; bleeding pattern; combined oral contraceptive; cycle control; estradiol valerate/dienogest; women.

Conflict of interest statement

Disclosure ZZ is an employee of Bayer Healthcare. SP is an employee of Bayer Pharmaceuticals. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Disposition of the study population.
Figure 2
Figure 2
Kaplan–Meier plot of time to pregnancy during the 13 cycles of estradiol valerate/dienogest treatment in the full analysis set (n=954).

References

    1. Gallo MF, Nanda K, Grimes DA, Schulz KF. 20 mcg versus >20 mcg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2005;(2):CD003989.
    1. Gerstman BB, Piper JM, Tomita DK, Ferguson WJ, Stadel BV, Lundin FE. Oral contraceptive estrogen dose and the risk of deep venous throm-boembolic disease. Am J Epidemiol. 1991;133(1):32–37.
    1. Serup J, Bostofte E, Larsen S, Westergaard J. Effectivity and acceptability of oral contraceptives containing natural and artificial estrogens in combination with a gestagen. A controlled double-blind investigation. Acta Obstet Gynecol Scand. 1981;60(2):203–206.
    1. Wenzl R, Bennink HC, van Beek A, Spona J, Huber J. Ovulation inhibition with a combined oral contraceptive containing 1 mg micronized 17 beta-estradiol. Fertil Steril. 1993;60(4):616–619.
    1. Caruso S, Iraci M, Cianci S, Casella E, Fava V, Cianci A. Quality of life and sexual function of women affected by endometriosis-associated pelvic pain when treated with dienogest. J Endocrinol Invest. 2015;38(11):1211–1218.
    1. Lagana AS, Vitale SG, Granese R, et al. Clinical dynamics of dienogest for the treatment of endometriosis: from bench to bedside. Expert Opin Drug Metab Toxicol. 2017;13(6):593–596.
    1. Lagana AS, Vitale SG, Muscia V, et al. Endometrial preparation with dienogest before hysteroscopic surgery: a systematic review. Arch Gynecol Obstet. 2017;295(3):661–667.
    1. Bayer HealthCare Pharmaceuticals Inc Natazia®: prescribing information. 2010. [Accessed 25 October 2016]. Available from: .
    1. Bayer Pharma AG. Qlaira®: summary of product characteristics. 2010. [Accessed 25 October 2016]. Available from: .
    1. Government of Canada Natazia®: product monograph. 2015. [Accessed 25 October 2016]. Available from: .
    1. Bayer Australia Limited Qlaira® (oestradiol valerate/dienogest): product information. 2009. [Accessed 25 October 2016]. Available from: .
    1. Singapore Government Health Sciences Authority Qlaira film coated tablet. 2011. [Accessed 25 October 2016]. Available from: .
    1. Ahrendt HJ, Makalova D, Parke S, Mellinger U, Mansour D. Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel. Contraception. 2009;80(5):436–444.
    1. Gerlinger C, Endrikat J, van der Meulen EA, Dieben TO, Dusterberg B. Recommendation for confidence interval and sample size calculation for the Pearl Index. Eur J Contracept Reprod Health Care. 2003;8(2):87–92.
    1. Belsey EM, Machin D, d’Arcangues C. The analysis of vaginal bleeding patterns induced by fertility regulating methods. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction. Contraception. 1986;34(3):253–260.
    1. World Health Organisation Family planning/contraception: fact sheet no 351. 2015. [Accessed June 15, 2016]. Available from: .
    1. Najafi-Sharjabad F, Zainiyah Syed Yahya S, Abdul Rahman H, Hanafiah Juni M, Abdul Manaf R. Barriers of modern contraceptive practices among Asian women: a mini literature review. Glob J Health Sci. 2013;5(5):181–192.
    1. Jensen JT, Parke S, Mellinger U, Serrani M, Mabey RG., Jr Hormone withdrawal-associated symptoms: comparison of oestradiol valerate/dienogest versus ethinylestradiol/norgestimate. Eur J Contracept Reprod Health Care. 2013;18(4):274–283.
    1. Nelson A, Parke S, Mellinger U, Zampaglione E, Schmidt A. Efficacy and safety of a combined oral contraceptive containing estradiol valerate/dienogest: results from a clinical study conducted in North America. J Womens Health (Larchmt) 2014;23(3):204–210.
    1. Palacios S, Wildt L, Parke S, Machlitt A, Romer T, Bitzer J. Efficacy and safety of a novel oral contraceptive based on oestradiol (oestradiol valerate/dienogest): a Phase III trial. Eur J Obstet Gynecol Reprod Biol. 2010;149(1):57–62.
    1. Endrikat J, Parke S, Trummer D, Schmidt W, Duijkers I, Klipping C. Ovulation inhibition with four variations of a four-phasic estradiol valerate/dienogest combined oral contraceptive: results of two prospective, randomized, open-label studies. Contraception. 2008;78(3):218–225.
    1. Teichmann A, Apter D, Emerich J, et al. Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial. Contraception. 2009;80(6):504–511.
    1. Anderson FD, Gibbons W, Portman D. Safety and efficacy of an extended-regimen oral contraceptive utilizing continuous low-dose ethinyl estradiol. Contraception. 2006;73(3):229–234.
    1. Nakajima ST, Archer DF, Ellman H. Efficacy and safety of a new 24-day oral contraceptive regimen of norethindrone acetate 1 mg/ethinyl estradiol 20 micro g (Loestrin 24 Fe) Contraception. 2007;75(1):16–22.
    1. Mircette® Study Group An open-label, multicenter, noncomparative safety and efficacy study of Mircette™, a low-dose estrogen-progestin oral contraceptive. Am J Obstet Gynecol. 1998;179(1):S2–S8.
    1. Di Carlo C, Gargano V, De Rosa N, Tommaselli GA, Sparice S, Nappi C. Effects of estradiol valerate and dienogest on quality of life and sexual function according to age. Gynecol Endocrinol. 2014;30(12):925–928.
    1. Caruso S, Agnello C, Romano M, et al. Preliminary study on the effect of four-phasic estradiol valerate and dienogest (E2V/DNG) oral contraceptive on the quality of sexual life. J Sex Med. 2011;8(10):2841–2850.
    1. Grandi G, Xholli A, Napolitano A, Palma F, Cagnacci A. Pelvic pain and quality of life of women with endometriosis during quadriphasic estradiol valerate/dienogest oral contraceptive: a patient-preference prospective 24-week pilot study. Reprod Sci. 2015;22(5):626–632.
    1. Graziottin A. Contraception containing estradiol valerate and dienogest–advantages, adherence and user satisfaction. Minerva Ginecol. 2014;66(5):479–495.

Source: PubMed

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