Цель. Провести сравнительную оценку влияния препарата, содержащего 0,03 мг этинилэстрадиола (ЭЭ) и 3 мг дроспиренона (ДРСП), на состояние кожи и антропометрические показатели по сравнению с препаратом, содержащим 0,02 мг ЭЭ и 3 мг ДРСП. Материалы и методы. В проспективное сравнительное рандомизированное исследование были включены 40 женщин репродуктивного возраста без противопоказаний к применению комбинированного орального контрацептива (КОК). Первую группу составили 20 женщин, которым назначена комбинация 0,03 мг ЭЭ и 3 мг ДРСП согласно инструкции по схеме 21/7; во 2-ю группу включены 20 пациенток, которым назначена комбинация 0,02 мг ЭЭ и 3 мг ДРСП согласно инструкции по схеме 24/4. Протокол исследования включал 8 визитов: на 0-м проводилась оценка критериев включения и исключения, 1-м – рандомизация пациентки (метод конвертов) и назначение препарата, 2–7-м (один раз в месяц) – выполнялись измерение артериального давления, определение антропометрических показателей: массы тела, роста, окружности талии, окружности бедер; определение индекса массы тела, оценка степени гирсутизма (шкала Ферримана–Галвея), оценка жирности кожи и волос, акне (по 10-балльной визуальной шкале). Результаты. Комбинация 0,03 мг ЭЭ и 3 мг ДРСП в течение 6 мес приема не оказывает значительного влияния на массу и индекс массы тела, окружность талии и бедер. К 6-му месяцу приема комбинация 0,03 мг ЭЭ и 3 мг ДРСП приводит к статистически значимому уменьшению жирности кожи и выраженности акне, а также уменьшению проявлений гирсутизма, что сопоставимо с клинической эффективностью комбинации 0,02 мг ЭЭ и 3 мг ДРСП. Выводы. Комбинация 0,03 мг ЭЭ и 3 мг ДРСП обладает сходным с комбинацией 0,02 мг ЭЭ и 3 мг ДРСП влиянием на жирность кожи, выраженность акне и гирсутизм, также не оказывая значимого воздействия на основные антропометрические показатели. Вероятно, влияние на уровень андрогенов и жировую ткань ДРСП-содержащих КОК обусловлено именно влиянием ДРСП, а не дозой ЭЭ.
Aim. To compare effects of the drug containing ethinylestradiol (EE) 0.03 mg and drospirenone (DRSP) 3 mg and the drug containing EE 0.02 mg and DRSP 3 mg on the skin and anthropometric parameters. Materials and methods. A prospective comparative randomized study included 40 women of reproductive age who didn’t have contraindications to use of combined oral contraceptive (COCs). The first group consisted of 20 women who were administrated EE 0.03 mg and DRSP 3 mg in the 21/7 regimen according to a prescribing information; the 2nd group included 20 patients who were administrated EE 0.02 mg and DRSP 3 mg in the 24/4 regimen according to a prescribing information. The study protocol included 8 visits: at the 0th visit, the inclusion and exclusion criteria were evaluated, at the 1st visit patient were randomized (envelope method) to receive one or another drug, at the 2nd – 7th visits (once a month) blood pressure was measured, anthropometric parameters were determined including body weight, height, waist, hips as well as body mass index, a degree of hirsutism (with Ferriman–Gallwey scale), skin and hair skin oiliness, acne (with a 10-point visual scale) were evaluated. Results. The use of EE 0.03 mg and DRSP 3 mg for 6 months did not significantly affect the body weight and body mass index, waist and hips. In the 6th month, the use of EE 0.03 mg and DRSP 3 mg lead to a statistically significant decrease in skin oiliness, severity of acne and hirsutism, which was comparable to a clinical effectiveness of EE 0.02 mg and DRSP 3 mg. Conclusions. EE 0.03 mg and DRSP 3 mg has a similar effect on skin oiliness, severity of acne and hirsutism with EE 0.02 mg and DRSP 3 mg, without significantly affecting the main anthropometric parameters. It is likely that the effect of DRSP-containing COCs on androgen levels and adipose tissue is due precisely to the effect of DRSP, and not to the dose of EE.
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2. Regidor PA, Schindler AE. Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone. Oncotarget 2017; 8 (47): 83334–42. DOI: 10.18632/oncotarget.19833. eCollection 2017 Oct 10.
3. Angelova M, Kovachev E, Miteva K, Atanasova Z. New Low-Dose Oral Contraceptive with 28 Midiana. Akush Ginekol (Sofiia) 2016; 55 (6): 16–8.
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[Dzhes. Instruktsiia k preparatu (in Russian).]
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7. Koltun W, Maloney JM, Marr J, Kunz M. Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 mg plus drospirenone 3 mg administered in a 24/4 regimen: a pooled analysis. Eur J Obstet Gynecol Reprod Biol 2011; 155 (2): 171–5. DOI: 10.1016/j.ejogrb.2010.12.027
8. Palli MB, Reyes-Habito CM, Lima XT, Kimball AB. A single-center, randomized double-blind, parallel-group study to examine the safety and efficacy of 3mg drospirenone/0.02 mg ethinyl estradiol compared with placebo in the treatment of moderate truncal acne vulgaris.
J Drugs Dermatol 2013; 12 (6): 633–7.
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10. Lello S, Pacifico V, Primavera G et al. Short-term effect of an estroprogestin containing ethinylestradiol 20 mcg + drospirenone 3 mg in 24+4 regimen at hormonal and cutaneous level in ovarian hyperandrogenism. Minerva Ginecol 2010; 62 (6): 509–13.
11. Joish VN, Boklage S, Lynen R et al. Use of drospirenone/ethinyl estradiol (DRSP/EE) among women with acne reduces acne treatment-related resources. J Med Econ 2011; 14 (6): 681–9. DOI: 10.3111/13696998.2011.617803
12. Tan JKL, Ediriweera C. Efficacy and safety of combined ethinyl estradiol/drospirenone oral contraceptives in the treatment of acne Int J Womens Health 2009; 1: 213–21.
13. De Nadai MN, Nobre F, Ferriani RA, Vieira CS. Effects of two contraceptives containing drospirenone on blood pressure in normotensive women: a randomized-controlled trial. Blood Press Monit 2015; 20 (6): 310–5. DOI: 10.1097/MBP.0000000000000139
14. Артымук Н.В., Букреева Е.Л. Сравнительная оценка влияния сочетания 3 мг дроспиренона и 20 или 30 мкг этинилэстрадиола на состояние кожи и антропометрические показатели. Фарматека. 2015; 3.
[Artymuk N.V., Bukreeva E.L. Sravnitel'naia otsenka vliianiia sochetaniia 3 mg drospirenona i 20 ili 30 mkg etinilestradiola na sostoianie kozhi i antropometricheskie pokazateli. Farmateka. 2015; 3 (in Russian).]
15. Bhattacharya SM, Jha A, DasMukhopadhyay L. Comparison of two contraceptive pills containing drospirenone and 20 mg or 30 mg ethinyl estradiol for polycystic ovary syndrome. Int J Gynaecol Obstet 2016; 132 (2): 210–3. DOI: 10.1016/j.ijgo.2015.06.065
16. Romualdi D, De Cicco S, Busacca M et al. Clinical efficacy and metabolic impact of two different dosages of ethinyl-estradiol in association with drospirenone in normal-weight women with polycystic ovary syndrome: a randomized study. J Endocrinol Invest 2013; 36 (8): 636–41.
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[Medical eligibility criteria for contraceptive methods of the Russian Federation. Moscow, 2013 (in Russian).]
18. Rezk M, Sayyed T, Ellakwa H et al. Metabolic changes in overweight and obese women above 35 years using Ethinylestradiol/drosperinone combined contraceptive pills: a 3-year case-control study. Gynecol Endocrinol 2016; 32: 844–7. https://doi.org/10.1080/09513590.2016.1179727
19. Armani A, Cinti F, Marzolla V et al. Mineralocorticoid receptor antagonism induces browning of white adipose tissue through impairment of autophagy and prevents adipocyte dysfunction in high-fat-diet-fed mice. FASEB J 2014; 28: 3745–57. https://doi.org/10.1096/fj.13-245415
20. Rocha M, Sanudo A, Bagatin E. The effect on acne quality of life of topical azelaic acid 15% gel versus a combined oral contraceptive in adult female acne: A randomized trial. Dermatoendocrinol 2017; 9 (1): e1361572. DOI: 10.1080/19381980.2017.1361572. eCollection 2017.
21. Gallo MF, Lopez LM, Grimes DA et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev 2008; 4. CD003987.
22. Guang-Sheng F, Mei-Lu B, Li-Nan C et al. Efficacy and safety of the combined oral contraceptive ethinylestradiol/drospirenone (Yasmin) in healthy Chinese women: a randomized, open-label, controlled, multicentre trial. Clin Drug Invest 2010; 30 (6): 387–96.
DOI: 10.2165/11318460-000000000-00000
________________________________________________
1. Drospirenone. Drugs and Lactation Database (LactMed). Bethesda (MD): National Library of Medicine (US); 2006. PMID: 30000415.
2. Regidor PA, Schindler AE. Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone. Oncotarget 2017; 8 (47): 83334–42. DOI: 10.18632/oncotarget.19833. eCollection 2017 Oct 10.
3. Angelova M, Kovachev E, Miteva K, Atanasova Z. New Low-Dose Oral Contraceptive with 28 Midiana. Akush Ginekol (Sofiia) 2016; 55 (6): 16–8.
4. Klipping C, Duijkers I, Fortier MP et al. Contraceptive efficacy and tolerability of ethinylestradiol 20 mg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study. J Fam Plann Reprod Health Care 2012; 38: 73–83. https://doi.org/10.1136/jfprhc-2011-100213
5. Dzhes. Instruktsiia k preparatu (in Russian).
6. Maloney JM, Dietze PJr, Watson D et al. A randomized controlled trial of a low-dose combined oral contraceptive containing 3 mg drospirenone plus 20 microg ethinylestradiol in the treatment of acne vulgaris: lesion counts, investigator ratings and subject self-assessment. J Drugs Dermatol 2009; 8 (9): 837–44.
7. Koltun W, Maloney JM, Marr J, Kunz M. Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 mg plus drospirenone 3 mg administered in a 24/4 regimen: a pooled analysis. Eur J Obstet Gynecol Reprod Biol 2011; 155 (2): 171–5. DOI: 10.1016/j.ejogrb.2010.12.027
8. Palli MB, Reyes-Habito CM, Lima XT, Kimball AB. A single-center, randomized double-blind, parallel-group study to examine the safety and efficacy of 3mg drospirenone/0.02 mg ethinyl estradiol compared with placebo in the treatment of moderate truncal acne vulgaris.
J Drugs Dermatol 2013; 12 (6): 633–7.
9. Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev 2012; 7: CD004425. DOI: 10.1002/14651858.CD004425.pub6
10. Lello S, Pacifico V, Primavera G et al. Short-term effect of an estroprogestin containing ethinylestradiol 20 mcg + drospirenone 3 mg in 24+4 regimen at hormonal and cutaneous level in ovarian hyperandrogenism. Minerva Ginecol 2010; 62 (6): 509–13.
11. Joish VN, Boklage S, Lynen R et al. Use of drospirenone/ethinyl estradiol (DRSP/EE) among women with acne reduces acne treatment-related resources. J Med Econ 2011; 14 (6): 681–9. DOI: 10.3111/13696998.2011.617803
12. Tan JKL, Ediriweera C. Efficacy and safety of combined ethinyl estradiol/drospirenone oral contraceptives in the treatment of acne Int J Womens Health 2009; 1: 213–21.
13. De Nadai MN, Nobre F, Ferriani RA, Vieira CS. Effects of two contraceptives containing drospirenone on blood pressure in normotensive women: a randomized-controlled trial. Blood Press Monit 2015; 20 (6): 310–5. DOI: 10.1097/MBP.0000000000000139
14. Artymuk N.V., Bukreeva E.L. Sravnitel'naia otsenka vliianiia sochetaniia 3 mg drospirenona i 20 ili 30 mkg etinilestradiola na sostoianie kozhi i antropometricheskie pokazateli. Farmateka. 2015; 3 (in Russian).
15. Bhattacharya SM, Jha A, DasMukhopadhyay L. Comparison of two contraceptive pills containing drospirenone and 20 mg or 30 mg ethinyl estradiol for polycystic ovary syndrome. Int J Gynaecol Obstet 2016; 132 (2): 210–3. DOI: 10.1016/j.ijgo.2015.06.065
16. Romualdi D, De Cicco S, Busacca M et al. Clinical efficacy and metabolic impact of two different dosages of ethinyl-estradiol in association with drospirenone in normal-weight women with polycystic ovary syndrome: a randomized study. J Endocrinol Invest 2013; 36 (8): 636–41.
17. Medical eligibility criteria for contraceptive methods of the Russian Federation. Moscow, 2013 (in Russian).
18. Rezk M, Sayyed T, Ellakwa H et al. Metabolic changes in overweight and obese women above 35 years using Ethinylestradiol/drosperinone combined contraceptive pills: a 3-year case-control study. Gynecol Endocrinol 2016; 32: 844–7. https://doi.org/10.1080/09513590.2016.1179727
19. Armani A, Cinti F, Marzolla V et al. Mineralocorticoid receptor antagonism induces browning of white adipose tissue through impairment of autophagy and prevents adipocyte dysfunction in high-fat-diet-fed mice. FASEB J 2014; 28: 3745–57. https://doi.org/10.1096/fj.13-245415
20. Rocha M, Sanudo A, Bagatin E. The effect on acne quality of life of topical azelaic acid 15% gel versus a combined oral contraceptive in adult female acne: A randomized trial. Dermatoendocrinol 2017; 9 (1): e1361572. DOI: 10.1080/19381980.2017.1361572. eCollection 2017.
21. Gallo MF, Lopez LM, Grimes DA et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev 2008; 4. CD003987.
22. Guang-Sheng F, Mei-Lu B, Li-Nan C et al. Efficacy and safety of the combined oral contraceptive ethinylestradiol/drospirenone (Yasmin) in healthy Chinese women: a randomized, open-label, controlled, multicentre trial. Clin Drug Invest 2010; 30 (6): 387–96.
DOI: 10.2165/11318460-000000000-00000
Авторы
Н.В. Артымук*, О.А. Тачкова
ФГБОУ ВО «Кемеровский государственный медицинский университет» Минздрава России, Кемерово, Россия
*artymuk@gmail.com
________________________________________________
Natalia V. Artymuk*, Olga A. Tachkova
Kemerovo State Medical University, Kemerovo, Russia
*artymuk@gmail.com