Comparison of two drospirenone-containing oral contraceptives for their effect on the ovary, menstrual cycle, acne, and side-effect profile: 20 µg ethinylestradiol/3 mg drospirenone (24/4) versus 30 µg ethinylestradiol/3 mg drospirenone (21/7)

Yıl 2021, , 1099 - 1103, 01.11.2021

Aysun Tekeli Taşkömür , Özlem Erten , Berna Dilbaz

https://doi.org/10.28982/josam.1002126

Öz

Background/Aim: Serious side effects, depending on the length of the hormone-free interval and the estrogen dose, cause the discontinuation of combined oral contraceptives (COCs). Therefore, it is important to identify COCs with minimal side effects which provide effective contraception. This study aimed to compare the effects of two different drospirenone-containing oral contraceptives (COCs) on ovarian suppression, cycle control, premenstrual symptoms, pain, acne, and the incidence of side-effects.
Methods: This prospective randomized controlled study was conducted with eighty women aged between 17-40 years. Patients were randomized to either 3mg drospirenone/30mcg ethinylestradiol (21/7 tablets) (Group 1) or 3mg drospirenone/20mcg ethinylestradiol (24/4 tablets) (Group 2) COCs. On Day-3 of the pre-treatment cycle, menstrual cycle patterns, serum hormone and lipid levels, menstrual complaints were recorded, followed by an evaluation of Day-21 progesterone levels, sonographic evaluation of endometrial thickness and the ovaries. Same assessment was repeated after pill use and the findings of the two cycles were compared.
Results: Both COC formulations suppressed serum hormone levels, decreased endometrial thickness and reduced incidence of dysmenorrhea-dyspareunia, and acne while serum HDL-cholesterol level was increased. Progesterone, FSH and endometrial thickness were lower, and serum cholesterol level was higher in Group 2 (P=0.007, P=0.044, P<0.001, P=0.035; respectively). Breast tenderness was significantly less in Group 2 (P=0.02). The incidence of follicular development, menstrual irregularity, and a headache was higher in Group 1, but the difference was not significant except for headaches (P=0.027).
Conclusion: 24/4 tablets might be a better alternative to 21/7 tablets with the advantage of tolerability as well as providing effective contraception.

Anahtar Kelimeler

Combined oral contraceptive, Ovarian suppression, Premenstrual disorders, Side- effects

Kaynakça

• 1. Brynhildsen J. Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks. Ther Adv Drug Saf. 2014;5(5):201-13. doi: 10.1177/2042098614548857.
• 2. Skouby SO. Contraceptive use and behavior in the 21st century: a comprehensive study across five European countries. Eur J Contracept Reprod Health Care. 2004;9(2):57-68. doi: 10.1080/13625180410001715681.
• 3. Baerwald AR, Pierson RA. Ovarian follicular development during the use of oral contraception: a review. J Obstet Gynaecol Can. 2004;26(1):19-24. doi: 10.1016/s1701-2163(16)30692-2.
• 4. Endrikat J, Gerlinger C, Richard S, Rosenbaum P, Düsterberg B. Ovulation inhibition doses of progestins: a systematic review of the available literature and of marketed preparations worldwide. Contraception. 2011;84(6):549-57. doi: 10.1016/j.contraception.2011.04.009.
• 5. Milsom I, Korver T. Ovulation incidence with oral contraceptives: a literature review. J Fam Plann Reprod Health Care. 2008;34(4):237-46. doi: 10.1783/147118908786000451.
• 6. Burkman R, Bell C, Serfaty D. The evolution of combined oral contraception: improving the risk-to-benefit ratio. Contraception. 2011;84(1):19-34. doi: 10.1016/j.contraception.2010.11.004.
• 7. Rosenberg MJ, Waugh MS. Oral contraceptive discontinuation: a prospective evaluation of frequency and reasons. Am J Obstet Gynecol. 1998;179(3):577-82. doi: 10.1016/s0002-9378(98)70047-x.
• 8. London A, Jensen JT. Rationale for eliminating the hormone-free interval in modern oral contraceptives. Int J Gynaecol Obstet. 2016;134(1):8-12. doi: 10.1016/j.ijgo.2015.10.028.
• 9. WHO Guidelines Approved by the Guidelines Review Committee. Medical Eligibility Criteria for Contraceptive Use. Geneva: World Health Organization Copyright © World Health Organization 2015; https://www.who.int/publications/i/item/9789241549158
• 10. Mishell Jr DR. Premenstrual disorders: epidemiology and disease burden. Am J Manag Care. 2005;11(16 Suppl):S473-9.
• 11. Kroll R, Ackerman R, Feldman R, Howard B, Weiss H, Hsieh J, et al. Efficacy and safety of a 21/7-active combined oral contraceptive with continuous low-dose ethinyl estradiol. Contraception. 2016;93(3):249-56. doi: 10.1016/j.contraception.2015.10.007.
• 12. Nappi RE, Kaunitz AM, Bitzer J. Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians. Eur J Contracept Reprod Health Care. 2016;21(2):106-15. doi: 10.3109/13625187.2015.1107894.
• 13. Graziottin A. The shorter, the better: A review of the evidence for a shorter contraceptive hormone-free interval. Eur J Contracept Reprod Health Care. 2016;21(2):93-105. doi: 10.3109/13625187.2015.1077380
• 14. Bitzer J, Banal-Silao MJ, Ahrendt HJ, Restrepo J, Hardtke M, Wissinger-Graefenhahn U, et al. Hormone withdrawal-associated symptoms with ethinylestradiol 20 mug/drospirenone 3 mg (24/4 regimen) versus ethinylestradiol 20 mug/desogestrel 150 mug (21/7 regimen). IntJ Women's Health. 2015;7:501-509. doi: 10.2147/IJWH.S77942.
• 15. Baerwald AR, Olatunbosun OA, Pierson RA. Ovarian follicular development is initiated during the hormone-free interval of oral contraceptive use. Contraception. 2004;70(5):371-7. doi: 10.1016/j.contraception.2004.05.006.
• 16. Machado RB, Pompei LM, Andrade R, Nahas E, Guazzelli C, Wender MC, et al. Bleeding Pattern and Management of Unexpected Bleeding/Spotting with an Extended Regimen of a Combination of Ethinylestradiol 20 mcg and Drospirenone 3 mg. Int J Womens Health. 2020;12:235-42. doi: 10.2147/IJWH.S238294.
• 17. Endrikat J, Gerlinger C, Plettig K, Wessel J, Schmidt W, Grubb G, et al. A meta-analysis on the correlation between ovarian activity and the incidence of intermenstrual bleeding during low-dose oral contraceptive use. Gynecol Endocrinol. 2003;17(2):107-14.
• 18. Ferries-Rowe E, Corey E, Archer JS. Primary Dysmenorrhea: Diagnosis and Therapy. Obstet Gynecol. 2020;136(5):1047-58. doi: 10.1097/AOG.0000000000004096.
• 19. Appleton SM. Premenstrual Syndrome: Evidence-based Evaluation and Treatment. Clin Obstet Gynecol. 2018;61(1):52-61. doi: 10.1097/GRF.0000000000000339.
• 20. Silva-Bermudez LS, Toloza FJK, Perez-Matos MC. Effects of oral contraceptives on metabolic parameters in adult premenopausal women: a meta-analysis. Endocr Connect. 2020;9(10):978-98. doi: 10.1530/EC-20-0423.
• 21. Klipping C, Marr J. Effects of two combined oral contraceptives containing ethinyl estradiol 20 microg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism. Contraception. 2005;71(6):409-16. doi: 10.1016/j.contraception.2004.12.005.
• 22. Fenton C, Wellington K, Moen MD, Robinson DM. Drospirenone/ethinylestradiol 3mg/20microg (24/4 day regimen): a review of its use in contraception, premenstrual dysphoric disorder and moderate acne vulgaris. Drugs. 2007;67(12):1749-65. doi: 10.2165/00003495-200767120-00007.
• 23. Larivée N, Suissa S, Coulombe J, Tagalakis V, Filion KB. Drospirenone-Containing Oral Contraceptive Pills and the Risk of Venous Thromboembolism: An Assessment of Risk in First-Time Users and Restarters. Drug Saf. 2017;40(7):583-96. doi: 10.1007/s40264-017-0525-2.
• 24. Jaisamrarn U, Santibenchakul S. A comparison of combined oral contraceptives containing chlormadinone acetate versus drospirenone for the treatment of acne and dysmenorrhea: a randomized trial. Contracept Reprod Med. 2018;3:5. doi: 10.1186/s40834-018-0058-9.
• 25. Uysal G, Akkaya H, Cagli F, Tutus S, Tayyar AT. A comparison of two different oral contraceptives in patients with severe primary dysmenorrhoea. J Obstet Gynaecol. 2018;38(6):828-32. doi: 10.1080/01443615.2017.1410533.