Safety and Efficacy of Combined Oral Contraceptive Ethinyl Estradiol/Drospirenone (YAZ) in Chinese Women: A Single-Arm, Open-Label, Multicenter, Post-Authorization Study
- 23 Downloads
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.
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.
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.
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.
ClinicalTrials.gov identifier, NCT02710708; Center for Drug Evaluation (CDE), China Food and Drug Administration (CFDA) number: CTR20160203.
KeywordsCombined oral contraception Efficacy Safety Women’s Health YAZ
We thank all the participants of the study.
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.
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.
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.
All data generated or analyzed during this study are included in the published article or as supplementary information files.
- 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.
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.Google Scholar
- 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.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.PubMedCrossRefGoogle Scholar
- 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.CrossRefGoogle Scholar
- 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.CrossRefGoogle Scholar
- 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.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.PubMedPubMedCentralCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.Google Scholar
- 36.Latthe PM, Champaneria R, Khan KS. Dysmenorrhoea. BMJ Clin Evid. 2011;21:2011.Google Scholar
- 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.PubMedPubMedCentralCrossRefGoogle Scholar
- 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.PubMedPubMedCentralGoogle Scholar