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«Нейтралитет во всем», или «эндокринно-метаболический ноктюрн» комбинированного орального контрацептива на основе Е4/дроспиренона
© ООО «КОНСИЛИУМ МЕДИКУМ», 2025 г.
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Orazov MR, Radzinsky VE, Dolgov ED. "Neutrality in everything," or "endocrine-metabolic nocturne" of the combined oral contraceptive based on E4/drospirenone: A review. Gynecology. 2025;27(1):61–65. DOI: 10.26442/20795696.2025.1.203155
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Ключевые слова: комбинированные оральные контрацептивы, эндокринно-метаболический профиль, масса тела, эстетрол, дроспиренон
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One of the most controversial issues of modern gynecology is the study of the effect of combined oral contraceptives (COCs) on the endocrine-metabolic profile. Unfortunately, there are still hormonophobic prejudices in society about the adverse impact of COCs on body weight, carbohydrate metabolism, and lipid profile despite no evidence base for such judgments. Therefore, the purpose of the article is to analyze the effect of E4/drospirenone-based COCs on endocrine-metabolic parameters through the lens of evidence-based medicine.
Keywords: combined oral contraceptives, endocrine-metabolic profile, body weight, estetrol, drospirenone
2. Hall KS, Trussell J. Types of combined oral contraceptives used by US women. Contraception. 2012;86(6):659-65. DOI:10.1016/j.contraception.2012.05.017
3. Metz L, Isacco L, Redman LM. Effect of oral contraceptives on energy balance in women: A review of current knowledge and potential cellular mechanisms. Metabolism. 2022;126:154919. DOI:10.1016/j.metabol.2021.154919
4. San-Juan-Rodriguez A, Bes-Rastrollo M, Martinez-Gonzalez MA, et al. Oral contraceptives use and development of obesity in a Mediterranean cohort: the SUN (Seguimiento Universidad de Navarra) Project. Int J Obes (Lond). 2020;44(2):320-2. DOI:10.1038/s41366-019-0442-9
5. Bardaweel SK, Akour AA, Kilani MV. Current knowledge, attitude, and patterns of oral contraceptives utilization among women in Jordan. BMC Womens Health. 2015;15:117. DOI:10.1186/s12905-015-0275-1
6. Национальные медицинские критерии приемлемости методов контрацепции. 2023. Режим доступа: https://roag-portal.ru/materials. Ссылка активна на 10.10.2024 [Natsional'nye meditsinskie kriterii priemlemosti metodov kontratseptsii. 2023.Available at: https://roag-portal.ru/materials. Accessed: 10.10.2024 (in Russian)].
7. Schwers J, Eriksson G, Wiqvist N, Diczfalusy E. 15α-hydroxylation: A new pathway of estrogen metabolism in the human fetus and newborn. Biochimica et Biophysica Acta (BBA) – General Subjects. 2003;100(1):313-1. DOI:10.1016/0304-4165(65)90464-2
8. Schwers J, Govaerts-Videtsky M, Wiqvist N, Diczfalusy E. Metabolism of oestrone sulphate by the previable human foetus. Acta Endocrinol (Copenh). 1965;50(4):597-610. DOI:10.1530/acta.0.0500597
9. Mancuso S, Benagiano G, Dell'Acqua S, et al. Studies on the metabolism of C-19 steroids in the human foeto-placental unit. 4. Aromatisation and hydroxylation products formed by previable foetuses perfused withandrostenedione and testosterone. Acta Endocrinol (Copenh). 1968;57(2):208-27. DOI:10.1530/acta.0.0570208
10. Coelingh Bennink F, Holinka CF, Visser M, Coelingh Bennink HJ. Maternal and fetal estetrol levels during pregnancy. Climacteric. 2008;11(Suppl. 1):69-72. DOI:10.1080/13697130802056321
11. Gérard C, Arnal JF, Jost M, et al. Profile of estetrol, a promising native estrogen for oral contraception and the relief of climacteric symptoms of menopause. Expert Rev Clin Pharmacol. 2022;15(2):121-37. DOI:10.1080/17512433.2022.2054413
12. Fruzzetti F, Fidecicchi T, Montt Guevara MM, Simoncini T. Estetrol: A New Choice for Contraception. J Clin Med. 2021;10(23):5625. DOI:10.3390/jcm10235625
13. Klipping C, Duijkers I, Mawet M, et al. Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone. Contraception. 2021;103(4):213-21. DOI:10.1016/j.contraception.2021.01.001
14. Douxfils J, Gaspard U, Taziaux M, et al. Impact of estetrol (E4) on hemostasis, metabolism and bone turnover in postmenopausal women. Climacteric. 2023;26(1):55-63. DOI:10.1080/13697137.2022.2139599
15. Geraghty P, Taylor HS. The next generation of oral contraception: advances in estrogens. ObGyn Management, June, 2021. Available at: https://cdn.mdedge.com/files/s3fs-public/obgm_the_next_generation_of_oral_contraception_v8.pdf. Accessed: 15.01.2025.
16. Apter D, Zimmerman Y, Beekman L, et al. Estetrol combined with drospirenone: an oral contraceptive with high acceptability, user satisfaction, well-being and favourable body weight control. Eur J Contracept Reprod Health Care. 2017;22(4):260-6. DOI:10.1080/13625187.2017.1336532
17. Coelingh Bennink HJ, Heegaard AM, Visser M, et al. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric. 2008;11(Suppl. 1):2-14. DOI:10.1080/13697130701798692
18. De Mello WC, Frohlich ED. Clinical perspectives and fundamental aspects of local cardiovascular and renal Renin-Angiotensin systems. Front Endocrinol (Lausanne). 2014;5:16. DOI:10.3389/fendo.2014.00016
19. De Mello WC. Chemical Communication between Heart Cells is Disrupted by Intracellular Renin and Angiotensin II: Implications for Heart Development and Disease. Front Endocrinol (Lausanne). 2015;6:72. DOI:10.3389/fendo.2015.00072
20. Bader M. ACE2, angiotensin-(1–7), and Mas: the other side of the coin. Pflugers Arch – Eur J Physiol. 2012;465(1):79-85. DOI:10.1007/s00424-012-1120-0
21. Losert W, Casals-Stenzel J, Buse M. Progestogens with antimineralocorticoid activity. Arzneimittelforschung. 1985;35(2):459-71.
22. Pérez-López FR. Clinical experiences with drospirenone: From reproductive to postmenopausal years. Maturitas. 2008;60(2):78-91. DOI:10.1016/j.maturitas.2008.03.009
23. Оразов М.Р., Ермаков В.В., Новгинов Д.С. Влияние контрацептива, содержащего эстетрол/дроспиренон, на сексуальную функцию женщин репродуктивного возраста. Гинекология. 2023;25(1):102-5 [Orazov MR, Ermakov VV, Novginov DS. Effect of an estetrol/drospirenone contraceptive on sexual function in women of reproductive age. Gynecology. 2023;25(1):102-5 (in Russian)]. DOI:10.26442/20795696.2023.1.202033
24. Оразов М.Р., Радзинский В.Е., Долгов Е.Д., Ермаков В.В. Эндокринно-метаболические эффекты оральных контрацептивов, содержащих эстетрол и дроспиренон. Вопросы гинекологии, акушерства и перинатологии. 2022;21(4):146-50 [Orazov MR, Radzinskii VE, Dolgov ED, Ermakov VV. Endokrinno-metabolicheskie effekty oral'nykh kontratseptivov, soderzhashchikh estetrol i drospirenon. Voprosy ginekologii, akusherstva i perinatologii. 2022;21(4):146-50 (in Russian)]. DOI:10.20953/1726-1678-2022-4-146-150
25. Оразов М.Р., Радзинский В.Е., Долгов Е.Д., Ермаков В.В. Риски венозных тромбоэмболий при использовании гормональных контрацептивов, содержащих эстетрол и дроспиренон. Вопросы гинекологии, акушерства и перинатологии. 2022;21(6):125-30 [Orazov MR, Radzinskii VE, Dolgov ED, Ermakov VV. Riski venoznykh tromboembolii pri ispol'zovanii gormonal'nykh kontratseptivov, soderzhashchikh estetrol i drospirenon. Voprosy ginekologii, akusherstva i perinatologii. 2022;21(6):125-30 (in Russian)]. DOI:10.20953/1726-1678-2022-6-125-130
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1. Radzinskii VE, Orazov MR, Dolgov ED. Dobrokachestvennaia displaziia molochnoi zhelezy i mastalgiia. Kombinirovannye oral'nye kontratseptivy na osnove estetrola i drospirenona. Akusherstvo i ginekologiia: novosti, mneniia, obuchenie. 2025;13(Suppl.):102-8 (in Russian). DOI:10.33029/2303-9698-2025-13-suppl-102-108
2. Hall KS, Trussell J. Types of combined oral contraceptives used by US women. Contraception. 2012;86(6):659-65. DOI:10.1016/j.contraception.2012.05.017
3. Metz L, Isacco L, Redman LM. Effect of oral contraceptives on energy balance in women: A review of current knowledge and potential cellular mechanisms. Metabolism. 2022;126:154919. DOI:10.1016/j.metabol.2021.154919
4. San-Juan-Rodriguez A, Bes-Rastrollo M, Martinez-Gonzalez MA, et al. Oral contraceptives use and development of obesity in a Mediterranean cohort: the SUN (Seguimiento Universidad de Navarra) Project. Int J Obes (Lond). 2020;44(2):320-2. DOI:10.1038/s41366-019-0442-9
5. Bardaweel SK, Akour AA, Kilani MV. Current knowledge, attitude, and patterns of oral contraceptives utilization among women in Jordan. BMC Womens Health. 2015;15:117. DOI:10.1186/s12905-015-0275-1
6. Natsional'nye meditsinskie kriterii priemlemosti metodov kontratseptsii. 2023.Available at: https://roag-portal.ru/materials. Accessed: 10.10.2024 (in Russian).
7. Schwers J, Eriksson G, Wiqvist N, Diczfalusy E. 15α-hydroxylation: A new pathway of estrogen metabolism in the human fetus and newborn. Biochimica et Biophysica Acta (BBA) – General Subjects. 2003;100(1):313-1. DOI:10.1016/0304-4165(65)90464-2
8. Schwers J, Govaerts-Videtsky M, Wiqvist N, Diczfalusy E. Metabolism of oestrone sulphate by the previable human foetus. Acta Endocrinol (Copenh). 1965;50(4):597-610. DOI:10.1530/acta.0.0500597
9. Mancuso S, Benagiano G, Dell'Acqua S, et al. Studies on the metabolism of C-19 steroids in the human foeto-placental unit. 4. Aromatisation and hydroxylation products formed by previable foetuses perfused withandrostenedione and testosterone. Acta Endocrinol (Copenh). 1968;57(2):208-27. DOI:10.1530/acta.0.0570208
10. Coelingh Bennink F, Holinka CF, Visser M, Coelingh Bennink HJ. Maternal and fetal estetrol levels during pregnancy. Climacteric. 2008;11(Suppl. 1):69-72. DOI:10.1080/13697130802056321
11. Gérard C, Arnal JF, Jost M, et al. Profile of estetrol, a promising native estrogen for oral contraception and the relief of climacteric symptoms of menopause. Expert Rev Clin Pharmacol. 2022;15(2):121-37. DOI:10.1080/17512433.2022.2054413
12. Fruzzetti F, Fidecicchi T, Montt Guevara MM, Simoncini T. Estetrol: A New Choice for Contraception. J Clin Med. 2021;10(23):5625. DOI:10.3390/jcm10235625
13. Klipping C, Duijkers I, Mawet M, et al. Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone. Contraception. 2021;103(4):213-21. DOI:10.1016/j.contraception.2021.01.001
14. Douxfils J, Gaspard U, Taziaux M, et al. Impact of estetrol (E4) on hemostasis, metabolism and bone turnover in postmenopausal women. Climacteric. 2023;26(1):55-63. DOI:10.1080/13697137.2022.2139599
15. Geraghty P, Taylor HS. The next generation of oral contraception: advances in estrogens. ObGyn Management, June, 2021. Available at: https://cdn.mdedge.com/files/s3fs-public/obgm_the_next_generation_of_oral_contraception_v8.pdf. Accessed: 15.01.2025.
16. Apter D, Zimmerman Y, Beekman L, et al. Estetrol combined with drospirenone: an oral contraceptive with high acceptability, user satisfaction, well-being and favourable body weight control. Eur J Contracept Reprod Health Care. 2017;22(4):260-6. DOI:10.1080/13625187.2017.1336532
17. Coelingh Bennink HJ, Heegaard AM, Visser M, et al. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric. 2008;11(Suppl. 1):2-14. DOI:10.1080/13697130701798692
18. De Mello WC, Frohlich ED. Clinical perspectives and fundamental aspects of local cardiovascular and renal Renin-Angiotensin systems. Front Endocrinol (Lausanne). 2014;5:16. DOI:10.3389/fendo.2014.00016
19. De Mello WC. Chemical Communication between Heart Cells is Disrupted by Intracellular Renin and Angiotensin II: Implications for Heart Development and Disease. Front Endocrinol (Lausanne). 2015;6:72. DOI:10.3389/fendo.2015.00072
20. Bader M. ACE2, angiotensin-(1–7), and Mas: the other side of the coin. Pflugers Arch – Eur J Physiol. 2012;465(1):79-85. DOI:10.1007/s00424-012-1120-0
21. Losert W, Casals-Stenzel J, Buse M. Progestogens with antimineralocorticoid activity. Arzneimittelforschung. 1985;35(2):459-71.
22. Pérez-López FR. Clinical experiences with drospirenone: From reproductive to postmenopausal years. Maturitas. 2008;60(2):78-91. DOI:10.1016/j.maturitas.2008.03.009
23. Orazov MR, Ermakov VV, Novginov DS. Effect of an estetrol/drospirenone contraceptive on sexual function in women of reproductive age. Gynecology. 2023;25(1):102-5 (in Russian). DOI:10.26442/20795696.2023.1.202033
24. Orazov MR, Radzinskii VE, Dolgov ED, Ermakov VV. Endokrinno-metabolicheskie effekty oral'nykh kontratseptivov, soderzhashchikh estetrol i drospirenon. Voprosy ginekologii, akusherstva i perinatologii. 2022;21(4):146-50 (in Russian). DOI:10.20953/1726-1678-2022-4-146-150
25. Orazov MR, Radzinskii VE, Dolgov ED, Ermakov VV. Riski venoznykh tromboembolii pri ispol'zovanii gormonal'nykh kontratseptivov, soderzhashchikh estetrol i drospirenon. Voprosy ginekologii, akusherstva i perinatologii. 2022;21(6):125-30 (in Russian). DOI:10.20953/1726-1678-2022-6-125-130
ФГАОУ ВО «Российский университет дружбы народов им. Патриса Лумумбы», Москва, Россия
*omekan@mail.ru
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Mekan R. Orazov*, Viktor E. Radzinsky, Evgeny D. Dolgov
Patrice Lumumba People’s Friendship University of Russia (RUDN University), Moscow, Russia
*omekan@mail.ru