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Эстетрол: новый эстрогенный компонент в составе комбинированных оральных контрацептивов
Эстетрол: новый эстрогенный компонент в составе комбинированных оральных контрацептивов
Хамадьянова А.У., Тухтабоев А.Х., Шафиева В.А., Колодяжная Е.А., Мансурова Ю.Р., Муратова А.А., Андреева А.А., Музафарова Ю.А. Эстетрол: новый эстрогенный компонент в составе комбинированных оральных контрацептивов. Гинекология. 2022;24(6):459–464. DOI: 10.26442/20795696.2022.6.201749
© ООО «КОНСИЛИУМ МЕДИКУМ», 2022 г.
© ООО «КОНСИЛИУМ МЕДИКУМ», 2022 г.
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Аннотация
Эстетрол (E4) – стероидный гормон, который обнаружен в 1965 г. в моче беременных женщин. E4 вырабатывается только во время беременности и попадает в материнский кровоток через плаценту. Его концентрация в материнской плазме человека увеличивается во время беременности, достигая максимума к концу беременности (≥1 нг/мл). Фармакологические свойства Е4 делают его полезным лекарственным средством для гормональной терапии и контрацепции. На сегодняшний день исследования II и III фазы показали многообещающие результаты с использованием комбинации 15 мг Е4/3 мг дроспиренона: этот комбинированный оральный контрацептив показал хороший эффект с нейтральным метаболическим действием. Тем не менее до сих пор очень мало известно о влиянии новой комбинации на молочную железу и костную ткань. Необходимо проведение дальнейших исследований для консолидации имеющихся данных и изучения возможных побочных эффектов при длительном применении Е4-содержащих комбинированных оральных контрацептивов по сравнению с известными этинилэстрадиол- и эстрадиолсодержащими комбинациями.
Ключевые слова: эстетрол, гормональная контрацепция, эстроген, гормональная терапия
Keywords: estetrol, hormonal contraception, estrogen, hormonal therapy
Ключевые слова: эстетрол, гормональная контрацепция, эстроген, гормональная терапия
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Keywords: estetrol, hormonal contraception, estrogen, hormonal therapy
Полный текст
Список литературы
1. Hagen AA, Barr M, Diczfalusy E. Metabolism of 17-beta-oestradiol-4-14-c in early infancy. Acta Endocrinol (Copenh). 1965;49:207-20.
2. Schwers J, Eriksson G, Diczfalusy E. 15alpha-hydroxylation: a new pathway of estrogen metabolism in the human fetus and newborn. Biochim Biophys Acta. 1965;100:313-6. DOI:10.1016/0304-4165(65)90464-2
3. Coelingh Bennink F, Holinka CF, Visser M, Coelingh Bennink HJ. Maternal and fetal estetrol levels during pregnancy. Climacteric. 2008;11(1):69-72. DOI:10.1080/13697130802056321
4. Kundu N, Wachs M, Iverson GB, Petersen LP. Comparison of serum unconjugated estriol and estetrol in normal and complicated pregnancies. Obstet Gynecol. 1981;58(3):276-81.
5. Visser M, Coelingh Bennink HJ. Clinical applications for estetrol. J Steroid Biochem Mol Biol. 2009;114(1-2):85-9. DOI:10.1016/j.jsbmb.2008.12.013
6. Visser M, Holinka CF, Coelingh Bennink HJ. First human exposure to exogenous single-dose oral estetrol in early postmenopausal women. Climacteric. 2008;11(1):31-40. DOI:10.1080/13697130802056511
7. Visser M, Foidart JM, Coelingh Bennink HJ. In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism. Climacteric. 2008;11(1):64-8. DOI:10.1080/13697130802050340
8. Hammond GL, Hogeveen KN, Visser M, Coelingh Bennink HJ. Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells. Climacteric. 2008;11(1):41-6. DOI:10.1080/13697130701851814
9. Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11(1):47-58. DOI:10.1080/13697130802073425
10. Holinka CF, Brincat M, Coelingh Bennink HJ. Preventive effect of oral estetrol in a menopausal hot flush model. Climacteric. 2008;11(1):15-21. DOI:10.1080/13697130701822807
11. Abot A, Fontaine C, Buscato M, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014;6(10):1328-46. DOI:10.15252/emmm.201404112
12. Valéra MC, Noirrit-Esclassan E, Dupuis M, et al. Effect of estetrol, a selective nuclear estrogen receptor modulator, in mouse models of arterial and venous thrombosis. Mol Cell Endocrinol. 2018;477:132-9. DOI:10.1016/j.mce.2018.06.010
13. Benoit T, Valera MC, Fontaine C, et al. Estetrol, a Fetal Selective Estrogen Receptor Modulator, Acts on the Vagina of Mice through Nuclear Estrogen Receptor α Activation. Am J Pathol. 2017;187(11):2499-507. DOI:10.1016/j.ajpath.2017.07.013
14. Foidart JM, Gaspard U, Pequeux C, et al. Sex Steroids’ Effects on Brain, Heart and Vessels. Unique Vascular Benefits of Estetrol, a Native Fetal Estrogen with Specific Actions in Tissues (NEST). Springer: Cham, Switzerland, 2019; p 169-95.
15. Coelingh Bennink HJ, Heegaard AM, Visser M, et al. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric. 2008;11(1):2-14. DOI:10.1080/13697130701798692
16. Pluchino N, Drakopoulos P, Casarosa E, et al. Effect of estetrol on Beta-Endorphin level in female rats. Steroids. 2015;95:104-10. DOI:10.1016/j.steroids.2015.01.003
17. Pluchino N, Santoro AN, Casarosa E, et al. Effect of estetrol administration on brain and serum allopregnanolone in intact and ovariectomized rats. J Steroid Biochem Mol Biol. 2014;143:285-90. DOI:10.1016/j.jsbmb.2014.04.011
18. Giretti MS, Montt Guevara MM, Cecchi E, et al. Effects of Estetrol on Migration and Invasion in T47-D Breast Cancer Cells through the Actin Cytoskeleton. Front Endocrinol (Lausanne). 2014;5:80. DOI:10.3389/fendo.2014.00080
19. Gérard C, Blacher S, Communal L, et al. Estetrol is a weak estrogen antagonizing estradiol-dependent mammary gland proliferation. J Endocrinol. 2015;224(1):85-95. DOI:10.1530/JOE-14-0549
20. Singer CF, Bennink HJ, Natter C, et al. Antiestrogenic effects of the fetal estrogen estetrol in women with estrogen-receptor positive early breast cancer. Carcinogenesis. 2014;35(11):2447-51. DOI:10.1093/carcin/bgu144
21. Schmidt M, Lenhard H, Hoenig A, et al. Tumor suppression, dose-limiting toxicity and wellbeing with the fetal estrogen estetrol in patients with advanced breast cancer. J Cancer Res Clin Oncol. 2021;147(6):1833-42. DOI:10.1007/s00432-020-03472-8
22. Gallez A, Dias Da Silva I, Wuidar V, et al. Estetrol and Mammary Gland: Friends or Foes? J Mammary Gland Biol Neoplasia. 2021;26(3):297-308. DOI:10.1007/s10911-021-09497-0
23. Liu S, Ruan X, Schultz S, et al. Oestetrol stimulates proliferation and oestrogen receptor expression in breast cancer cell lines: comparison of four oestrogens. Eur J Contracept Reprod Health Care. 2015;20(1):29-35. DOI:10.3109/13625187.2014.951997
24. Jozan S, Kreitmann B, Bayard F. Different effects of oestradiol, oestriol, oestetrol and of oestrone on human breast cancer cells (MCF-7) in long term tissue culture. Acta Endocrinol (Copenh). 1981;98(1):73-80. DOI:10.1530/acta.0.0980073
25. Coelingh Bennink HJT, Singer C, Simoncini T, et al. Estetrol, a pregnancy-specific human steroid, prevents and suppresses mammary tumor growth in a rat model. Climacteric. 2008;11(1):29. DOI:10.1080/13697130802040325
26. Visser M, Kloosterboer HJ, Bennink HJ. Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model. Horm Mol Biol Clin Investig. 2012;9(1):95-103. DOI:10.1515/hmbci-2012-0015
27. Coelingh Bennink HJ, Skouby S, Bouchard P, Holinka CF. Ovulation inhibition by estetrol in an in vivo model. Contraception. 2008;77(3):186-90. DOI:10.1016/j.contraception.2007.11.014
28. Visser M, Coelingh Bennink HJT. Estetrol, the new natural estrogen for clinical use in women. Ref Gynecol Obstet. 2011;14:427-32.
29. Duijkers IJ, Klipping C, Zimmerman Y, et al. Inhibition of ovulation by administration of estetrol in combination with drospirenone or levonorgestrel: Results of a phase II dose-finding pilot study. Eur J Contracept Reprod Health Care. 2015;20(6):476-89. DOI:10.3109/13625187.2015.1074675
30. Apter D, Zimmerman Y, Beekman L, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results fr om a phase II, randomised, dose-finding study (FIESTA). Contraception. 2016;94(4):366-73. DOI:10.1016/j.contraception.2016.04.015
31. 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):260-7. DOI:10.1080/13625187.2017.1336532
32. Creinin MD, Westhoff CL, Bouchard C, et al. Estetrol-drospirenone combination oral contraceptive: North American phase 3 efficacy and safety results. Contraception. 2021;104(3):222-8. DOI:10.1016/j.contraception.2021.05.002
33. Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:5298. DOI:10.1136/bmj.f5298
34. Farris M, Bastianelli C, Rosato E, et al. Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis. Expert Rev Clin Pharmacol. 2017;10(10):1129-44. DOI:10.1080/17512433.2017.1356718
35. Montt-Guevara MM, Palla G, Spina S, et al. Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration. Maturitas. 2017;99:1-9. DOI:10.1016/j.maturitas.2017.02.005
36. Kluft C, Zimmerman Y, Mawet M, et al. Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol. Contraception. 2017;95(2):140-7. DOI:10.1016/j.contraception.2016.08.018
37. Douxfils J, Klipping C, Duijkers I, et al. Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters. Contraception. 2020;102(6):396-402. DOI:10.1016/j.contraception.2020.08.015
38. Rahman MS, Woollard K. Atherosclerosis. Adv Exp Med Biol. 2017;1003:121-44. DOI:10.1007/978-3-319-57613-8_7
39. Arnal JF, Scarabin PY, Trémollières F, et al. Estrogens in vascular biology and disease: wh ere do we stand today? Curr Opin Lipidol. 2007;18(5):554-60. DOI:10.1097/MOL.0b013e3282ef3bca
40. Hodgin JB, Krege JH, Reddick RL, et al. Estrogen receptor alpha is a major mediator of 17beta-estradiol's atheroprotective effects on lesion size in Apoe-/- mice. J Clin Invest. 2001;107(3):333-40. DOI:10.1172/JCI11320
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50. Coelingh Bennink HJT, Verhoeven C, Zimmerman Y, et al. Pharmacokinetics of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women. Climacteric. 2017;20(3):285-9. DOI:10.1080/13697137.2017.1291608
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52. 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
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2. Schwers J, Eriksson G, Diczfalusy E. 15alpha-hydroxylation: a new pathway of estrogen metabolism in the human fetus and newborn. Biochim Biophys Acta. 1965;100:313-6. DOI:10.1016/0304-4165(65)90464-2
3. Coelingh Bennink F, Holinka CF, Visser M, Coelingh Bennink HJ. Maternal and fetal estetrol levels during pregnancy. Climacteric. 2008;11(1):69-72. DOI:10.1080/13697130802056321
4. Kundu N, Wachs M, Iverson GB, Petersen LP. Comparison of serum unconjugated estriol and estetrol in normal and complicated pregnancies. Obstet Gynecol. 1981;58(3):276-81.
5. Visser M, Coelingh Bennink HJ. Clinical applications for estetrol. J Steroid Biochem Mol Biol. 2009;114(1-2):85-9. DOI:10.1016/j.jsbmb.2008.12.013
6. Visser M, Holinka CF, Coelingh Bennink HJ. First human exposure to exogenous single-dose oral estetrol in early postmenopausal women. Climacteric. 2008;11(1):31-40. DOI:10.1080/13697130802056511
7. Visser M, Foidart JM, Coelingh Bennink HJ. In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism. Climacteric. 2008;11(1):64-8. DOI:10.1080/13697130802050340
8. Hammond GL, Hogeveen KN, Visser M, Coelingh Bennink HJ. Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells. Climacteric. 2008;11(1):41-6. DOI:10.1080/13697130701851814
9. Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11(1):47-58. DOI:10.1080/13697130802073425
10. Holinka CF, Brincat M, Coelingh Bennink HJ. Preventive effect of oral estetrol in a menopausal hot flush model. Climacteric. 2008;11(1):15-21. DOI:10.1080/13697130701822807
11. Abot A, Fontaine C, Buscato M, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014;6(10):1328-46. DOI:10.15252/emmm.201404112
12. Valéra MC, Noirrit-Esclassan E, Dupuis M, et al. Effect of estetrol, a selective nuclear estrogen receptor modulator, in mouse models of arterial and venous thrombosis. Mol Cell Endocrinol. 2018;477:132-9. DOI:10.1016/j.mce.2018.06.010
13. Benoit T, Valera MC, Fontaine C, et al. Estetrol, a Fetal Selective Estrogen Receptor Modulator, Acts on the Vagina of Mice through Nuclear Estrogen Receptor α Activation. Am J Pathol. 2017;187(11):2499-507. DOI:10.1016/j.ajpath.2017.07.013
14. Foidart JM, Gaspard U, Pequeux C, et al. Sex Steroids’ Effects on Brain, Heart and Vessels. Unique Vascular Benefits of Estetrol, a Native Fetal Estrogen with Specific Actions in Tissues (NEST). Springer: Cham, Switzerland, 2019; p 169-95.
15. Coelingh Bennink HJ, Heegaard AM, Visser M, et al. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric. 2008;11(1):2-14. DOI:10.1080/13697130701798692
16. Pluchino N, Drakopoulos P, Casarosa E, et al. Effect of estetrol on Beta-Endorphin level in female rats. Steroids. 2015;95:104-10. DOI:10.1016/j.steroids.2015.01.003
17. Pluchino N, Santoro AN, Casarosa E, et al. Effect of estetrol administration on brain and serum allopregnanolone in intact and ovariectomized rats. J Steroid Biochem Mol Biol. 2014;143:285-90. DOI:10.1016/j.jsbmb.2014.04.011
18. Giretti MS, Montt Guevara MM, Cecchi E, et al. Effects of Estetrol on Migration and Invasion in T47-D Breast Cancer Cells through the Actin Cytoskeleton. Front Endocrinol (Lausanne). 2014;5:80. DOI:10.3389/fendo.2014.00080
19. Gérard C, Blacher S, Communal L, et al. Estetrol is a weak estrogen antagonizing estradiol-dependent mammary gland proliferation. J Endocrinol. 2015;224(1):85-95. DOI:10.1530/JOE-14-0549
20. Singer CF, Bennink HJ, Natter C, et al. Antiestrogenic effects of the fetal estrogen estetrol in women with estrogen-receptor positive early breast cancer. Carcinogenesis. 2014;35(11):2447-51. DOI:10.1093/carcin/bgu144
21. Schmidt M, Lenhard H, Hoenig A, et al. Tumor suppression, dose-limiting toxicity and wellbeing with the fetal estrogen estetrol in patients with advanced breast cancer. J Cancer Res Clin Oncol. 2021;147(6):1833-42. DOI:10.1007/s00432-020-03472-8
22. Gallez A, Dias Da Silva I, Wuidar V, et al. Estetrol and Mammary Gland: Friends or Foes? J Mammary Gland Biol Neoplasia. 2021;26(3):297-308. DOI:10.1007/s10911-021-09497-0
23. Liu S, Ruan X, Schultz S, et al. Oestetrol stimulates proliferation and oestrogen receptor expression in breast cancer cell lines: comparison of four oestrogens. Eur J Contracept Reprod Health Care. 2015;20(1):29-35. DOI:10.3109/13625187.2014.951997
24. Jozan S, Kreitmann B, Bayard F. Different effects of oestradiol, oestriol, oestetrol and of oestrone on human breast cancer cells (MCF-7) in long term tissue culture. Acta Endocrinol (Copenh). 1981;98(1):73-80. DOI:10.1530/acta.0.0980073
25. Coelingh Bennink HJT, Singer C, Simoncini T, et al. Estetrol, a pregnancy-specific human steroid, prevents and suppresses mammary tumor growth in a rat model. Climacteric. 2008;11(1):29. DOI:10.1080/13697130802040325
26. Visser M, Kloosterboer HJ, Bennink HJ. Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model. Horm Mol Biol Clin Investig. 2012;9(1):95-103. DOI:10.1515/hmbci-2012-0015
27. Coelingh Bennink HJ, Skouby S, Bouchard P, Holinka CF. Ovulation inhibition by estetrol in an in vivo model. Contraception. 2008;77(3):186-90. DOI:10.1016/j.contraception.2007.11.014
28. Visser M, Coelingh Bennink HJT. Estetrol, the new natural estrogen for clinical use in women. Ref Gynecol Obstet. 2011;14:427-32.
29. Duijkers IJ, Klipping C, Zimmerman Y, et al. Inhibition of ovulation by administration of estetrol in combination with drospirenone or levonorgestrel: Results of a phase II dose-finding pilot study. Eur J Contracept Reprod Health Care. 2015;20(6):476-89. DOI:10.3109/13625187.2015.1074675
30. Apter D, Zimmerman Y, Beekman L, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results fr om a phase II, randomised, dose-finding study (FIESTA). Contraception. 2016;94(4):366-73. DOI:10.1016/j.contraception.2016.04.015
31. 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):260-7. DOI:10.1080/13625187.2017.1336532
32. Creinin MD, Westhoff CL, Bouchard C, et al. Estetrol-drospirenone combination oral contraceptive: North American phase 3 efficacy and safety results. Contraception. 2021;104(3):222-8. DOI:10.1016/j.contraception.2021.05.002
33. Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:5298. DOI:10.1136/bmj.f5298
34. Farris M, Bastianelli C, Rosato E, et al. Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis. Expert Rev Clin Pharmacol. 2017;10(10):1129-44. DOI:10.1080/17512433.2017.1356718
35. Montt-Guevara MM, Palla G, Spina S, et al. Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration. Maturitas. 2017;99:1-9. DOI:10.1016/j.maturitas.2017.02.005
36. Kluft C, Zimmerman Y, Mawet M, et al. Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol. Contraception. 2017;95(2):140-7. DOI:10.1016/j.contraception.2016.08.018
37. Douxfils J, Klipping C, Duijkers I, et al. Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters. Contraception. 2020;102(6):396-402. DOI:10.1016/j.contraception.2020.08.015
38. Rahman MS, Woollard K. Atherosclerosis. Adv Exp Med Biol. 2017;1003:121-44. DOI:10.1007/978-3-319-57613-8_7
39. Arnal JF, Scarabin PY, Trémollières F, et al. Estrogens in vascular biology and disease: wh ere do we stand today? Curr Opin Lipidol. 2007;18(5):554-60. DOI:10.1097/MOL.0b013e3282ef3bca
40. Hodgin JB, Krege JH, Reddick RL, et al. Estrogen receptor alpha is a major mediator of 17beta-estradiol's atheroprotective effects on lesion size in Apoe-/- mice. J Clin Invest. 2001;107(3):333-40. DOI:10.1172/JCI11320
41. Billon-Galés A, Fontaine C, Douin-Echinard V, et al. Endothelial estrogen receptor-alpha plays a crucial role in the atheroprotective action of 17beta-estradiol in low-density lipoprotein receptor-deficient mice. Circulation. 2009;120(25):2567-76. DOI:10.1161/CIRCULATIONAHA.109.898445
42. Pollow DP Jr, Romero-Aleshire MJ, Sanchez JN, et al. ANG II-induced hypertension in the VCD mouse model of menopause is prevented by estrogen replacement during perimenopause. Am J Physiol Regul Integr Comp Physiol. 2015;309(12):1546-52. DOI:10.1152/ajpregu.00170.2015
43. Tarhouni K, Freidja ML, Guihot AL, et al. Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries. Am J Physiol Heart Circ Physiol. 2014;307(4):504-14. DOI:10.1152/ajpheart.00986.2013
44. Darblade B, Pendaries C, Krust A, et al. Estradiol alters nitric oxide production in the mouse aorta through the alpha-, but not beta-, estrogen receptor. Circ Res. 2002;90(4):413-9. DOI:10.1161/hh0402.105096
45. Brouchet L, Krust A, Dupont S, et al. Estradiol accelerates reendothelialization in mouse carotid artery through estrogen receptor-alpha but not estrogen receptor-beta. Circulation. 2001;103(3):423-8. DOI:10.1161/01.cir.103.3.423
46. Smirnova NF, Fontaine C, Buscato M, et al. The Activation Function-1 of Estrogen Receptor Alpha Prevents Arterial Neointima Development Through a Direct Effect on Smooth Muscle Cells. Circ Res. 2015;117(9):770-8. DOI:10.1161/CIRCRESAHA.115.306416
47. Guivarc'h E, Buscato M, Guihot AL, et al. Predominant Role of Nuclear Versus Membrane Estrogen Receptor α in Arterial Protection: Implications for Estrogen Receptor α Modulation in Cardiovascular Prevention/Safety. J Am Heart Assoc. 2018;7(13):e008950. DOI:10.1161/JAHA.118.008950
48. Hilgers RH, Oparil S, Wouters W, Coelingh Bennink HJ. Vasorelaxing effects of estetrol in rat arteries. J Endocrinol. 2012;215(1):97-106. DOI:10.1530/JOE-12-0009
49. Montt-Guevara MM, Giretti MS, Russo E, et al. Estetrol Modulates Endothelial Nitric Oxide Synthesis in Human Endothelial Cells. Front Endocrinol (Lausanne). 2015;6:111. DOI:10.3389/fendo.2015.00111
50. Coelingh Bennink HJT, Verhoeven C, Zimmerman Y, et al. Pharmacokinetics of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women. Climacteric. 2017;20(3):285-9. DOI:10.1080/13697137.2017.1291608
51. Mawet M, Maillard C, Klipping C, et al. Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives. Eur J Contracept Reprod Health Care. 2015;20(6):463-75. DOI:10.3109/13625187.2015.1068934
52. 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
53. Raps M, Helmerhorst F, Fleischer K, et al. Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives. J Thromb Haemost. 2012;10(6):992-7. DOI:10.1111/j.1538-7836.2012.04720.x
54. Odlind V, Milsom I, Persson I, Victor A. Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills? Acta Obstet Gynecol Scand. 2002;81(6):482-90.
55. Coelingh Bennink HJT, Verhoeven C, Zimmerman Y, et al. Pharmacodynamic effects of the fetal estrogen estetrol in postmenopausal women: results from a multiple-rising-dose study. Menopause. 2017;24(6):677-85. DOI:10.1097/GME.0000000000000823
56. Gallez A, Blacher S, Maquoi E, et al. Estetrol Combined to Progestogen for Menopause or Contraception Indication Is Neutral on Breast Cancer. Cancers (Basel). 2021;13(10):2486. DOI:10.3390/cancers13102486
2. Schwers J, Eriksson G, Diczfalusy E. 15alpha-hydroxylation: a new pathway of estrogen metabolism in the human fetus and newborn. Biochim Biophys Acta. 1965;100:313-6. DOI:10.1016/0304-4165(65)90464-2
3. Coelingh Bennink F, Holinka CF, Visser M, Coelingh Bennink HJ. Maternal and fetal estetrol levels during pregnancy. Climacteric. 2008;11(1):69-72. DOI:10.1080/13697130802056321
4. Kundu N, Wachs M, Iverson GB, Petersen LP. Comparison of serum unconjugated estriol and estetrol in normal and complicated pregnancies. Obstet Gynecol. 1981;58(3):276-81.
5. Visser M, Coelingh Bennink HJ. Clinical applications for estetrol. J Steroid Biochem Mol Biol. 2009;114(1-2):85-9. DOI:10.1016/j.jsbmb.2008.12.013
6. Visser M, Holinka CF, Coelingh Bennink HJ. First human exposure to exogenous single-dose oral estetrol in early postmenopausal women. Climacteric. 2008;11(1):31-40. DOI:10.1080/13697130802056511
7. Visser M, Foidart JM, Coelingh Bennink HJ. In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism. Climacteric. 2008;11(1):64-8. DOI:10.1080/13697130802050340
8. Hammond GL, Hogeveen KN, Visser M, Coelingh Bennink HJ. Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells. Climacteric. 2008;11(1):41-6. DOI:10.1080/13697130701851814
9. Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11(1):47-58. DOI:10.1080/13697130802073425
10. Holinka CF, Brincat M, Coelingh Bennink HJ. Preventive effect of oral estetrol in a menopausal hot flush model. Climacteric. 2008;11(1):15-21. DOI:10.1080/13697130701822807
11. Abot A, Fontaine C, Buscato M, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014;6(10):1328-46. DOI:10.15252/emmm.201404112
12. Valéra MC, Noirrit-Esclassan E, Dupuis M, et al. Effect of estetrol, a selective nuclear estrogen receptor modulator, in mouse models of arterial and venous thrombosis. Mol Cell Endocrinol. 2018;477:132-9. DOI:10.1016/j.mce.2018.06.010
13. Benoit T, Valera MC, Fontaine C, et al. Estetrol, a Fetal Selective Estrogen Receptor Modulator, Acts on the Vagina of Mice through Nuclear Estrogen Receptor α Activation. Am J Pathol. 2017;187(11):2499-507. DOI:10.1016/j.ajpath.2017.07.013
14. Foidart JM, Gaspard U, Pequeux C, et al. Sex Steroids’ Effects on Brain, Heart and Vessels. Unique Vascular Benefits of Estetrol, a Native Fetal Estrogen with Specific Actions in Tissues (NEST). Springer: Cham, Switzerland, 2019; p 169-95.
15. Coelingh Bennink HJ, Heegaard AM, Visser M, et al. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric. 2008;11(1):2-14. DOI:10.1080/13697130701798692
16. Pluchino N, Drakopoulos P, Casarosa E, et al. Effect of estetrol on Beta-Endorphin level in female rats. Steroids. 2015;95:104-10. DOI:10.1016/j.steroids.2015.01.003
17. Pluchino N, Santoro AN, Casarosa E, et al. Effect of estetrol administration on brain and serum allopregnanolone in intact and ovariectomized rats. J Steroid Biochem Mol Biol. 2014;143:285-90. DOI:10.1016/j.jsbmb.2014.04.011
18. Giretti MS, Montt Guevara MM, Cecchi E, et al. Effects of Estetrol on Migration and Invasion in T47-D Breast Cancer Cells through the Actin Cytoskeleton. Front Endocrinol (Lausanne). 2014;5:80. DOI:10.3389/fendo.2014.00080
19. Gérard C, Blacher S, Communal L, et al. Estetrol is a weak estrogen antagonizing estradiol-dependent mammary gland proliferation. J Endocrinol. 2015;224(1):85-95. DOI:10.1530/JOE-14-0549
20. Singer CF, Bennink HJ, Natter C, et al. Antiestrogenic effects of the fetal estrogen estetrol in women with estrogen-receptor positive early breast cancer. Carcinogenesis. 2014;35(11):2447-51. DOI:10.1093/carcin/bgu144
21. Schmidt M, Lenhard H, Hoenig A, et al. Tumor suppression, dose-limiting toxicity and wellbeing with the fetal estrogen estetrol in patients with advanced breast cancer. J Cancer Res Clin Oncol. 2021;147(6):1833-42. DOI:10.1007/s00432-020-03472-8
22. Gallez A, Dias Da Silva I, Wuidar V, et al. Estetrol and Mammary Gland: Friends or Foes? J Mammary Gland Biol Neoplasia. 2021;26(3):297-308. DOI:10.1007/s10911-021-09497-0
23. Liu S, Ruan X, Schultz S, et al. Oestetrol stimulates proliferation and oestrogen receptor expression in breast cancer cell lines: comparison of four oestrogens. Eur J Contracept Reprod Health Care. 2015;20(1):29-35. DOI:10.3109/13625187.2014.951997
24. Jozan S, Kreitmann B, Bayard F. Different effects of oestradiol, oestriol, oestetrol and of oestrone on human breast cancer cells (MCF-7) in long term tissue culture. Acta Endocrinol (Copenh). 1981;98(1):73-80. DOI:10.1530/acta.0.0980073
25. Coelingh Bennink HJT, Singer C, Simoncini T, et al. Estetrol, a pregnancy-specific human steroid, prevents and suppresses mammary tumor growth in a rat model. Climacteric. 2008;11(1):29. DOI:10.1080/13697130802040325
26. Visser M, Kloosterboer HJ, Bennink HJ. Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model. Horm Mol Biol Clin Investig. 2012;9(1):95-103. DOI:10.1515/hmbci-2012-0015
27. Coelingh Bennink HJ, Skouby S, Bouchard P, Holinka CF. Ovulation inhibition by estetrol in an in vivo model. Contraception. 2008;77(3):186-90. DOI:10.1016/j.contraception.2007.11.014
28. Visser M, Coelingh Bennink HJT. Estetrol, the new natural estrogen for clinical use in women. Ref Gynecol Obstet. 2011;14:427-32.
29. Duijkers IJ, Klipping C, Zimmerman Y, et al. Inhibition of ovulation by administration of estetrol in combination with drospirenone or levonorgestrel: Results of a phase II dose-finding pilot study. Eur J Contracept Reprod Health Care. 2015;20(6):476-89. DOI:10.3109/13625187.2015.1074675
30. Apter D, Zimmerman Y, Beekman L, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results fr om a phase II, randomised, dose-finding study (FIESTA). Contraception. 2016;94(4):366-73. DOI:10.1016/j.contraception.2016.04.015
31. 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):260-7. DOI:10.1080/13625187.2017.1336532
32. Creinin MD, Westhoff CL, Bouchard C, et al. Estetrol-drospirenone combination oral contraceptive: North American phase 3 efficacy and safety results. Contraception. 2021;104(3):222-8. DOI:10.1016/j.contraception.2021.05.002
33. Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:5298. DOI:10.1136/bmj.f5298
34. Farris M, Bastianelli C, Rosato E, et al. Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis. Expert Rev Clin Pharmacol. 2017;10(10):1129-44. DOI:10.1080/17512433.2017.1356718
35. Montt-Guevara MM, Palla G, Spina S, et al. Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration. Maturitas. 2017;99:1-9. DOI:10.1016/j.maturitas.2017.02.005
36. Kluft C, Zimmerman Y, Mawet M, et al. Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol. Contraception. 2017;95(2):140-7. DOI:10.1016/j.contraception.2016.08.018
37. Douxfils J, Klipping C, Duijkers I, et al. Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters. Contraception. 2020;102(6):396-402. DOI:10.1016/j.contraception.2020.08.015
38. Rahman MS, Woollard K. Atherosclerosis. Adv Exp Med Biol. 2017;1003:121-44. DOI:10.1007/978-3-319-57613-8_7
39. Arnal JF, Scarabin PY, Trémollières F, et al. Estrogens in vascular biology and disease: wh ere do we stand today? Curr Opin Lipidol. 2007;18(5):554-60. DOI:10.1097/MOL.0b013e3282ef3bca
40. Hodgin JB, Krege JH, Reddick RL, et al. Estrogen receptor alpha is a major mediator of 17beta-estradiol's atheroprotective effects on lesion size in Apoe-/- mice. J Clin Invest. 2001;107(3):333-40. DOI:10.1172/JCI11320
41. Billon-Galés A, Fontaine C, Douin-Echinard V, et al. Endothelial estrogen receptor-alpha plays a crucial role in the atheroprotective action of 17beta-estradiol in low-density lipoprotein receptor-deficient mice. Circulation. 2009;120(25):2567-76. DOI:10.1161/CIRCULATIONAHA.109.898445
42. Pollow DP Jr, Romero-Aleshire MJ, Sanchez JN, et al. ANG II-induced hypertension in the VCD mouse model of menopause is prevented by estrogen replacement during perimenopause. Am J Physiol Regul Integr Comp Physiol. 2015;309(12):1546-52. DOI:10.1152/ajpregu.00170.2015
43. Tarhouni K, Freidja ML, Guihot AL, et al. Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries. Am J Physiol Heart Circ Physiol. 2014;307(4):504-14. DOI:10.1152/ajpheart.00986.2013
44. Darblade B, Pendaries C, Krust A, et al. Estradiol alters nitric oxide production in the mouse aorta through the alpha-, but not beta-, estrogen receptor. Circ Res. 2002;90(4):413-9. DOI:10.1161/hh0402.105096
45. Brouchet L, Krust A, Dupont S, et al. Estradiol accelerates reendothelialization in mouse carotid artery through estrogen receptor-alpha but not estrogen receptor-beta. Circulation. 2001;103(3):423-8. DOI:10.1161/01.cir.103.3.423
46. Smirnova NF, Fontaine C, Buscato M, et al. The Activation Function-1 of Estrogen Receptor Alpha Prevents Arterial Neointima Development Through a Direct Effect on Smooth Muscle Cells. Circ Res. 2015;117(9):770-8. DOI:10.1161/CIRCRESAHA.115.306416
47. Guivarc'h E, Buscato M, Guihot AL, et al. Predominant Role of Nuclear Versus Membrane Estrogen Receptor α in Arterial Protection: Implications for Estrogen Receptor α Modulation in Cardiovascular Prevention/Safety. J Am Heart Assoc. 2018;7(13):e008950. DOI:10.1161/JAHA.118.008950
48. Hilgers RH, Oparil S, Wouters W, Coelingh Bennink HJ. Vasorelaxing effects of estetrol in rat arteries. J Endocrinol. 2012;215(1):97-106. DOI:10.1530/JOE-12-0009
49. Montt-Guevara MM, Giretti MS, Russo E, et al. Estetrol Modulates Endothelial Nitric Oxide Synthesis in Human Endothelial Cells. Front Endocrinol (Lausanne). 2015;6:111. DOI:10.3389/fendo.2015.00111
50. Coelingh Bennink HJT, Verhoeven C, Zimmerman Y, et al. Pharmacokinetics of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women. Climacteric. 2017;20(3):285-9. DOI:10.1080/13697137.2017.1291608
51. Mawet M, Maillard C, Klipping C, et al. Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives. Eur J Contracept Reprod Health Care. 2015;20(6):463-75. DOI:10.3109/13625187.2015.1068934
52. 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
53. Raps M, Helmerhorst F, Fleischer K, et al. Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives. J Thromb Haemost. 2012;10(6):992-7. DOI:10.1111/j.1538-7836.2012.04720.x
54. Odlind V, Milsom I, Persson I, Victor A. Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills? Acta Obstet Gynecol Scand. 2002;81(6):482-90.
55. Coelingh Bennink HJT, Verhoeven C, Zimmerman Y, et al. Pharmacodynamic effects of the fetal estrogen estetrol in postmenopausal women: results from a multiple-rising-dose study. Menopause. 2017;24(6):677-85. DOI:10.1097/GME.0000000000000823
56. Gallez A, Blacher S, Maquoi E, et al. Estetrol Combined to Progestogen for Menopause or Contraception Indication Is Neutral on Breast Cancer. Cancers (Basel). 2021;13(10):2486. DOI:10.3390/cancers13102486
________________________________________________
2. Schwers J, Eriksson G, Diczfalusy E. 15alpha-hydroxylation: a new pathway of estrogen metabolism in the human fetus and newborn. Biochim Biophys Acta. 1965;100:313-6. DOI:10.1016/0304-4165(65)90464-2
3. Coelingh Bennink F, Holinka CF, Visser M, Coelingh Bennink HJ. Maternal and fetal estetrol levels during pregnancy. Climacteric. 2008;11(1):69-72. DOI:10.1080/13697130802056321
4. Kundu N, Wachs M, Iverson GB, Petersen LP. Comparison of serum unconjugated estriol and estetrol in normal and complicated pregnancies. Obstet Gynecol. 1981;58(3):276-81.
5. Visser M, Coelingh Bennink HJ. Clinical applications for estetrol. J Steroid Biochem Mol Biol. 2009;114(1-2):85-9. DOI:10.1016/j.jsbmb.2008.12.013
6. Visser M, Holinka CF, Coelingh Bennink HJ. First human exposure to exogenous single-dose oral estetrol in early postmenopausal women. Climacteric. 2008;11(1):31-40. DOI:10.1080/13697130802056511
7. Visser M, Foidart JM, Coelingh Bennink HJ. In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism. Climacteric. 2008;11(1):64-8. DOI:10.1080/13697130802050340
8. Hammond GL, Hogeveen KN, Visser M, Coelingh Bennink HJ. Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells. Climacteric. 2008;11(1):41-6. DOI:10.1080/13697130701851814
9. Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11(1):47-58. DOI:10.1080/13697130802073425
10. Holinka CF, Brincat M, Coelingh Bennink HJ. Preventive effect of oral estetrol in a menopausal hot flush model. Climacteric. 2008;11(1):15-21. DOI:10.1080/13697130701822807
11. Abot A, Fontaine C, Buscato M, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014;6(10):1328-46. DOI:10.15252/emmm.201404112
12. Valéra MC, Noirrit-Esclassan E, Dupuis M, et al. Effect of estetrol, a selective nuclear estrogen receptor modulator, in mouse models of arterial and venous thrombosis. Mol Cell Endocrinol. 2018;477:132-9. DOI:10.1016/j.mce.2018.06.010
13. Benoit T, Valera MC, Fontaine C, et al. Estetrol, a Fetal Selective Estrogen Receptor Modulator, Acts on the Vagina of Mice through Nuclear Estrogen Receptor α Activation. Am J Pathol. 2017;187(11):2499-507. DOI:10.1016/j.ajpath.2017.07.013
14. Foidart JM, Gaspard U, Pequeux C, et al. Sex Steroids’ Effects on Brain, Heart and Vessels. Unique Vascular Benefits of Estetrol, a Native Fetal Estrogen with Specific Actions in Tissues (NEST). Springer: Cham, Switzerland, 2019; p 169-95.
15. Coelingh Bennink HJ, Heegaard AM, Visser M, et al. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric. 2008;11(1):2-14. DOI:10.1080/13697130701798692
16. Pluchino N, Drakopoulos P, Casarosa E, et al. Effect of estetrol on Beta-Endorphin level in female rats. Steroids. 2015;95:104-10. DOI:10.1016/j.steroids.2015.01.003
17. Pluchino N, Santoro AN, Casarosa E, et al. Effect of estetrol administration on brain and serum allopregnanolone in intact and ovariectomized rats. J Steroid Biochem Mol Biol. 2014;143:285-90. DOI:10.1016/j.jsbmb.2014.04.011
18. Giretti MS, Montt Guevara MM, Cecchi E, et al. Effects of Estetrol on Migration and Invasion in T47-D Breast Cancer Cells through the Actin Cytoskeleton. Front Endocrinol (Lausanne). 2014;5:80. DOI:10.3389/fendo.2014.00080
19. Gérard C, Blacher S, Communal L, et al. Estetrol is a weak estrogen antagonizing estradiol-dependent mammary gland proliferation. J Endocrinol. 2015;224(1):85-95. DOI:10.1530/JOE-14-0549
20. Singer CF, Bennink HJ, Natter C, et al. Antiestrogenic effects of the fetal estrogen estetrol in women with estrogen-receptor positive early breast cancer. Carcinogenesis. 2014;35(11):2447-51. DOI:10.1093/carcin/bgu144
21. Schmidt M, Lenhard H, Hoenig A, et al. Tumor suppression, dose-limiting toxicity and wellbeing with the fetal estrogen estetrol in patients with advanced breast cancer. J Cancer Res Clin Oncol. 2021;147(6):1833-42. DOI:10.1007/s00432-020-03472-8
22. Gallez A, Dias Da Silva I, Wuidar V, et al. Estetrol and Mammary Gland: Friends or Foes? J Mammary Gland Biol Neoplasia. 2021;26(3):297-308. DOI:10.1007/s10911-021-09497-0
23. Liu S, Ruan X, Schultz S, et al. Oestetrol stimulates proliferation and oestrogen receptor expression in breast cancer cell lines: comparison of four oestrogens. Eur J Contracept Reprod Health Care. 2015;20(1):29-35. DOI:10.3109/13625187.2014.951997
24. Jozan S, Kreitmann B, Bayard F. Different effects of oestradiol, oestriol, oestetrol and of oestrone on human breast cancer cells (MCF-7) in long term tissue culture. Acta Endocrinol (Copenh). 1981;98(1):73-80. DOI:10.1530/acta.0.0980073
25. Coelingh Bennink HJT, Singer C, Simoncini T, et al. Estetrol, a pregnancy-specific human steroid, prevents and suppresses mammary tumor growth in a rat model. Climacteric. 2008;11(1):29. DOI:10.1080/13697130802040325
26. Visser M, Kloosterboer HJ, Bennink HJ. Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model. Horm Mol Biol Clin Investig. 2012;9(1):95-103. DOI:10.1515/hmbci-2012-0015
27. Coelingh Bennink HJ, Skouby S, Bouchard P, Holinka CF. Ovulation inhibition by estetrol in an in vivo model. Contraception. 2008;77(3):186-90. DOI:10.1016/j.contraception.2007.11.014
28. Visser M, Coelingh Bennink HJT. Estetrol, the new natural estrogen for clinical use in women. Ref Gynecol Obstet. 2011;14:427-32.
29. Duijkers IJ, Klipping C, Zimmerman Y, et al. Inhibition of ovulation by administration of estetrol in combination with drospirenone or levonorgestrel: Results of a phase II dose-finding pilot study. Eur J Contracept Reprod Health Care. 2015;20(6):476-89. DOI:10.3109/13625187.2015.1074675
30. Apter D, Zimmerman Y, Beekman L, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results fr om a phase II, randomised, dose-finding study (FIESTA). Contraception. 2016;94(4):366-73. DOI:10.1016/j.contraception.2016.04.015
31. 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):260-7. DOI:10.1080/13625187.2017.1336532
32. Creinin MD, Westhoff CL, Bouchard C, et al. Estetrol-drospirenone combination oral contraceptive: North American phase 3 efficacy and safety results. Contraception. 2021;104(3):222-8. DOI:10.1016/j.contraception.2021.05.002
33. Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:5298. DOI:10.1136/bmj.f5298
34. Farris M, Bastianelli C, Rosato E, et al. Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis. Expert Rev Clin Pharmacol. 2017;10(10):1129-44. DOI:10.1080/17512433.2017.1356718
35. Montt-Guevara MM, Palla G, Spina S, et al. Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration. Maturitas. 2017;99:1-9. DOI:10.1016/j.maturitas.2017.02.005
36. Kluft C, Zimmerman Y, Mawet M, et al. Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol. Contraception. 2017;95(2):140-7. DOI:10.1016/j.contraception.2016.08.018
37. Douxfils J, Klipping C, Duijkers I, et al. Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters. Contraception. 2020;102(6):396-402. DOI:10.1016/j.contraception.2020.08.015
38. Rahman MS, Woollard K. Atherosclerosis. Adv Exp Med Biol. 2017;1003:121-44. DOI:10.1007/978-3-319-57613-8_7
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Авторы
А.У. Хамадьянова*, А.Х. Тухтабоев, В.А. Шафиева, Е.А. Колодяжная, Ю.Р. Мансурова, А.А. Муратова, А.А. Андреева, Ю.А. Музафарова
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России, Уфа, Россия
*sagidullin12@bk.ru
Bashkir State Medical University, Ufa, Russia
*sagidullin12@bk.ru
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России, Уфа, Россия
*sagidullin12@bk.ru
________________________________________________
Bashkir State Medical University, Ufa, Russia
*sagidullin12@bk.ru
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