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Safety and Efficacy of Combined Oral Contraceptive Ethinyl Estradiol/Drospirenone (YAZ) in Chinese Women: A Single-Arm, Open-Label, Multicenter, Post-Authorization Study

Abstract

Introduction

The study was conducted to assess the safety and efficacy of a combined oral contraceptive, YAZ, containing 3 mg drospirenone/20 μg ethinyl estradiol administered in a 24/4 regimen.

Methods

This was a single-arm, open-label, interventional, post-authorization safety surveillance study of YAZ across 6 treatment cycles. Primary objective was assessing its safety profile in Chinese women. Secondary objectives included assessing contraceptive efficacy, cycle control, and bleeding patterns among subjects with and without preceding abortion, along with efficacy in moderate acne vulgaris. Subgroup analyses included assessing efficacy in the dysmenorrhea group using a visual analog scale. All variables were analyzed by descriptive statistical methods.

Results

Of 1921 women treated with YAZ (mean age: 29.9 ± 5.5 years), 12.9% reported adverse drug reactions. Most frequently reported adverse events were nausea (2.6%), breast pain (2.3%), and breast swelling (1.3%). Unintended pregnancy rate (adjusted Pearl Index) was 0.3 (n = 2 pregnancies, 95% confidence interval 0.1–1.2). Incidence of overall withdrawal bleeding (cycle 2–cycle 5) was 93.3%–95.2%, of which 87.8%–95.1% in post-abortion subjects and 94.0%–95.3% in subjects without preceding abortion. Intra-cyclic bleeding (cycle 2–cycle 6) decreased in the overall population (from 14.9 to 5.5%), post-abortion subgroup (32.4% to 6.9%), and in subjects without preceding abortion (12.4% to 5.3%). Incidence of onset of withdrawal bleeding < 7 days among abnormal uterine bleeding patients at baseline was 85.2% and 87.2% at cycles 2 and 5, respectively, and incidence of intra-cyclic bleeding was 23.5% and 8.0% at cycles 1 and 6, respectively. Mean percent change in total acne lesion count from baseline to cycle 6 was − 79.9% ,and mean change in pain severity due to dysmenorrhea was − 31.2 mm at cycle 6 when compared with baseline.

Conclusion

The 24/4 YAZ regimen showed good safety profile, contraceptive reliability, good cycle control along with subgroup of patients. Improvements in dysmenorrhea and acne were also observed. No events of venous thromboembolism/arterial thromboembolism were reported.

Trial Registration

ClinicalTrials.gov identifier, NCT02710708; Center for Drug Evaluation (CDE), China Food and Drug Administration (CFDA) number: CTR20160203.

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References

  1. 1.

    United Nations. World Contraceptive Patterns 2013. Department of Economic and Social Affairs, Population Division [Internet]. http://www.un.org/en/development/desa/population/publications/pdf/family/worldContraceptivePatternsWallChart2013.pdf.

  2. 2.

    Goodyear-Smith FA, Arroll B. Contraception before and after termination of pregnancy: can we do it better? N Z Med J. 2003;116:U683.

  3. 3.

    Wu L. A survey on the knowledge, attitude, and behavior regarding contraception use among pregnant teenagers in Beijing, China. Clin Nurs Res. 2010;19:403–15.

  4. 4.

    Rosenberg MJ, Waugh MS. Oral contraceptive discontinuation: a prospective evaluation of frequency and reasons. Am J Obstet Gynecol. 1998;179:577–82.

  5. 5.

    Bitzer J, Simon JA. Current issues and available options in combined hormonal contraception. Contraception. 2011;84:342–56.

  6. 6.

    Sulak PJ, Kuehl TJ, Ortiz M, Shull BL. Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms. Am J Obstet Gynecol. 2002;186:1142–9.

  7. 7.

    Willis SA, Kuehl TJ, Spiekerman AM, Sulak PJ. Greater inhibition of the pituitary–ovarian axis in oral contraceptive regimens with a shortened hormone-free interval. Contraception. 2006;74:100–3.

  8. 8.

    Sullivan H, Furniss H, Spona J, Elstein M. Effect of 21-day and 24-day oral contraceptive regimens containing gestodene (60 microg) and ethinyl estradiol (15 microg) on ovarian activity. Fertil Steril. 1999;72:115–20.

  9. 9.

    Bachmann G, Sulak PJ, Sampson-Landers C, Benda N, Marr J. Efficacy and safety of a low-dose 24-day combined oral contraceptive containing 20 micrograms ethinylestradiol and 3 mg drospirenone. Contraception. 2004;70:191–8.

  10. 10.

    Koltun W, Lucky AW, Thiboutot D, Niknian M, Sampson-Landers C, Korner P, et al. Efficacy and safety of 3 mg drospirenone/20 mcg ethinylestradiol oral contraceptive administered in 24/4 regimen in the treatment of acne vulgaris: a randomized, double-blind, placebo-controlled trial. Contraception. 2008;77:249–56.

  11. 11.

    Yonkers KA, Brown C, Pearlstein TB, Foegh M, Sampson-Landers C, Rapkin A. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol. 2005;106:492–501.

  12. 12.

    Fenton C, Wellington K, Moen MD, Robinson DM. Drospirenone/ethinylestradiol 3 mg/20microg (24/4 day regimen): a review of its use in contraception, premenstrual dysphoric disorder and moderate acne vulgaris. Drugs. 2007;67:1749–65.

  13. 13.

    Mishell DR. YAZ and the novel progestin drospirenone. J Reprod Med. 2008;53:721–8.

  14. 14.

    Marr J, Niknian M, Shulman LP, Lynen R. Premenstrual dysphoric disorder symptom cluster improvement by cycle with the combined oral contraceptive ethinylestradiol 20 mcg plus drospirenone 3 mg administered in a 24/4 regimen. Contraception. 2011;84:81–6.

  15. 15.

    Sangthawan M, Taneepanichskul S. A comparative study of monophasic oral contraceptives containing either drospirenone 3 mg or levonorgestrel 150 μg on premenstrual symptoms. Contraception. 2005;71:1–7.

  16. 16.

    Klipping C, Duijkers I, Trummer D, Marr J. Suppression of ovarian activity with a drospirenone-containing oral contraceptive in a 24/4 regimen. Contraception. 2008;78:16–25.

  17. 17.

    Sulak PJ, Scow RD, Preece C, Riggs MW, Kuehl TJ. Hormone withdrawal symptoms in oral contraceptive users. Obstet Gynecol. 2000;95:261–6.

  18. 18.

    Hernádi L, Marr J, Trummer D, De Leo V, Petraglia F. Efficacy and safety of a low-dose combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20 mcg in a 24/4-day regimen. Contraception. 2009;80:18–24.

  19. 19.

    Foidart JM, Wuttke W, Bouw GM, Gerlinger C, Heithecker R. A comparative investigation of contraceptive reliability, cycle control and tolerance of two monophasic oral contraceptives containing either drospirenone or desogestrel. Eur J Contracept Reprod Health Care. 2000;5:124–34.

  20. 20.

    Huber J, Foidart JM, Wuttke W, Merki-Feld GS, The HS, Gerlinger C, et al. Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone. Eur J Contracept Reprod Health Care. 2000;5:25–34.

  21. 21.

    Parsey KS, Pong A. An open-label, multicenter study to evaluate Yasmin, a low-dose combination oral contraceptive containing drospirenone, a new progestogen. Contraception. 2000;61:105–11.

  22. 22.

    Anttila L, Bachmann G, Hernádi L, Kunz M, Marr J, Klipping C. Contraceptive efficacy of a combined oral contraceptive containing ethinyloestradiol 20 μg/drospirenone 3 mg administered in a 24/4 regimen: a pooled analysis of four open-label studies. Eur J Obstet Gynecol Reprod Biol. 2011;155:180–2.

  23. 23.

    Wang C, Di W, Liao Q, Shen H, Han Z, Tang L, et al. Efficacy and safety of a combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20ug in a 24 + 4-day regimen in China. Chin J Obstet Gynecol. 2014;49:355–9.

  24. 24.

    COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) [Internet]. 2005. https://www.ema.europa.eu/documents/scientific-guideline/guideline-clinical-investigation-steroid-contraceptives-women_en.pdf.

  25. 25.

    Marr J, Gerlinger C, Kunz M. A historical cycle control comparison of two drospirenone-containing combined oral contraceptives: ethinylestradiol 30 μg/drospirenone 3 mg administered in a 21/7 regimen versus ethinylestradiol 20 μg/drospirenone 3 mg administered in a 24/4 regimen. Eur J Obstet Gynecol Reprod Biol. 2012;162:91–5.

  26. 26.

    Klipping C, Duijkers I, Fortier MP, Marr J, Trummer D, Elliesen J. Contraceptive efficacy and tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study. J Fam Plan Reprod Health Care. 2012;38:73–83.

  27. 27.

    Machado RB, de Melo NR, Maia H. Bleeding patterns and menstrual-related symptoms with the continuous use of a contraceptive combination of ethinylestradiol and drospirenone: a randomized study. Contraception. 2010;81:215–22.

  28. 28.

    Guang-Sheng F, Mei-Lu B, Li-Nan C, Xiao-Ming C, Zi-Rong H, Zi-Yan H, et al. Efficacy and Safety of the Combined Oral Contraceptive Ethinylestradiol/Drospirenone (Yasmin®) in Healthy Chinese Women: A Randomized, Open-Label, Controlled. Multicentre Trial. Clinical Drug Investigation. 2010;1:387–96.

  29. 29.

    Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for treatment of acne. In: The Cochrane Collaboration, editor. Cochrane Database of Systematic Reviews [Internet]. Chichester: John Wiley & Sons, Ltd; 2012 [cited 2018 Dec 4]. http://doi.wiley.com/10.1002/14651858.CD004425.pub6.

  30. 30.

    Ågren UM, Anttila M, Mäenpää-Liukko K, Rantala M-L, Rautiainen H, Sommer WF, et al. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function. Eur J Contracept Reprod Health Care. 2011;16:458–67.

  31. 31.

    Zimmerman Y, Eijkemans MJC, Coelingh Bennink HJT, Blankenstein MA, Fauser BCJM. The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis. Hum Reprod Update. 2014;20:76–105.

  32. 32.

    Maloney JM, Dietze P, Watson D, Niknian M, Lee-Rugh S, Sampson-Landers C, et al. Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol oral contraceptive administered in a 24/4 regimen: a randomized controlled trial. Obstet Gynecol. 2008;112:773–81.

  33. 33.

    Zhang G, Lin T, Sun Q. An oral contraceptive containing ethinyl estradiol and drospirenone for the treatment of women with moderate acne vulgaris: a randomized, multicenter, placebo-controlled clinical trial. Chin J Dermatol. 2015;48:85–9.

  34. 34.

    Kim N, Yoo H-N, Hyun HS, Lee D-Y, Yoon B-K, Choi D-S. Efficacy and safety of a 24-day regimen of drospirenone-containing combined oral contraceptive in Korean women. Obstet Gynecol Sci. 2015;58:397–400.

  35. 35.

    Proctor M, Farquhar C. Diagnosis and management of dysmenorrhoea. BMJ. 2006;332:1134–8.

  36. 36.

    Latthe PM, Champaneria R, Khan KS. Dysmenorrhoea. BMJ Clin Evid. 2011;21:2011.

  37. 37.

    Momoeda M, Kondo M, Elliesen J, Yasuda M, Yamamoto S, Harada T. Efficacy and safety of a flexible extended regimen of ethinylestradiol/drospirenone for the treatment of dysmenorrhea: a multicenter, randomized, open-label, active-controlled study. Int J Womens Health. 2017;9:295–305.

  38. 38.

    Momoeda M, Hayakawa M, Shimazaki Y, Mizunuma H, Taketani Y. Does the presence of coexisting diseases modulate the effectiveness of a low-dose estrogen/progestin, ethinylestradiol/drospirenone combination tablet in dysmenorrhea? Reanalysis of two randomized studies in Japanese women. Int J Womens Health. 2014;6:989–98.

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Acknowledgements

We thank all the participants of the study.

Funding

This study was funded by Bayer, China. The study sponsor also funded the journal’s Rapid Service Fee.

Medical Writing Assistance

Medical writing support under authors’ direction was provided by Priyanka Bannikoppa, PhD, (Indegene Pvt. Ltd., Bangalore) and funded by Bayer, China.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

List of Investigators

The full list of Investigators for this study can be found in the Supplementary Material.

Disclosures

Fangbo Qian, Yaojuan He, Xiangying Gu, and Wen Di declare that they have nothing to disclose. Xin Sun is an employee of Bayer Healthcare, China.

Compliance with Ethics Guidelines

This study was conducted in accordance with the Declaration of Helsinki, 1964, as revised in 2013 and the International Council for Harmonization guideline E6: Good Clinical Practice. The study was reviewed and approved by each study site’s Independent Ethics Committee (Supplementary Material). Springer’s policy concerning informed consent has been followed. The master ethics committees were the Renji Hospital Shanghai Jiaotong University School of Medicine and Tianjin Medical University General Hospital.

Data Availability

All data generated or analyzed during this study are included in the published article or as supplementary information files.

Author information

Correspondence to Wen Di.

Additional information

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Cite this article

Sun, X., Qian, F., He, Y. et al. Safety and Efficacy of Combined Oral Contraceptive Ethinyl Estradiol/Drospirenone (YAZ) in Chinese Women: A Single-Arm, Open-Label, Multicenter, Post-Authorization Study. Adv Ther (2020). https://doi.org/10.1007/s12325-019-01210-2

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Keywords

  • Combined oral contraception
  • Efficacy
  • Safety
  • Women’s Health
  • YAZ