В статье представлены современные литературные данные о методах экстренной контрацепции и принципах действия препаратов, применяемых с этой целью, их особенностях, влиянии на репродуктивную систему, эффективности, приемлемости, их влиянии на овуляцию и состояние эндометрия. Ключевые слова: экстренная контрацепция, левоноргестрел, мифепристон, улипристала ацетат.
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The article presents modern literature data on emergency contraceptive methods and the principles of the action of drugs used for this purpose, their characteristics, effects on the reproductive system, efficacy, acceptability, their effect on ovulation and the state of the endometrium.
1. ESHRE Capri Workshop Group Female contraception over 40. Human Reproduction Update 2009; 15 (6): 599–612.
2. American College of Obstetriciansand Gynecologist (ACOG) Statementon Contraceptive Methods 1998 A.
3. World Health Organization. Levonorgestrel for Emergency contraception. Geneva: WHO, 2005.
4. Haspels AA. Emergency Contraception: a Review. Contraception 1994; 50: 101–8.
5. Yuzpe AA, Turlow HJ, Ramzy I et al. Post-coital Contraception. Pilot Study. J Reprod Med 1974;13: 53–8.
6. Руководство по контрацепции. Под ред. В.Н.Прилепской. 2-е изд., перераб. и доп. М.: МЕДпресс-информ, 2014. / Rukovodstvo po kontratseptsii. Pod red. V.N.Prilepskoi. 2-e izd., pererab. i dop. M.: MEDpress-inform, 2014. [in Russian]
7. Van Look PF, Von Hertzen H. Emergency Contraception. Br Med Bull 1993; 49: 158–70.
8. Swahn ML, Bygdeman M, Cekan S et al. The Effect of RU 486 Administred during the Early Luteal Phase on Bleeding Pattern, Hormonal Parameters and Endometrium. Hum Reprod 1990; 5: 402–8.
9. European Medicines Agency public assessment report (EPAR) Ella One 2009; Apr. EMEA/H/C 1027.
10. Emergency contraception. A guidline for service provision in Europe. December 2013. Europen Consortium for Emergency Contraception.
11. Durand M, del Carmen Cravioto M, Raymond EG et al. On the mechanisms of action of short-term levonorgestrel administration in emergency contraception. Contraception 2001; 64 (4): 227–34.
12. Hamoda H, Ashok PW, Stalder C et al. A randomized trial of mifepristone (10 mg) and levonorgestrel for emergency contraception. Obstet Gynecol 2004; 6: 1307–13.
13. Arowojolu AO, Okewole IA, Adekunle AO. Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians. Contraception 2002; 4: 269–73.
14. Turok DK. The copper IUD and emergency contraception. Contraception 2011; 84 (2): 205–6.
15. Julia E Kohn, Deborah L. Nucatola EC4U: results fr om a project integrating the copper IUC into emergency contraceptive care. Contraception 2016.
16. Руководство по экстренной контрацепции. Под ред. В.Н.Прилепской. 2-е изд. М., 2010; с. 255. / Rukovodstvo po ekstrennoi kontratseptsii. Pod red. V.N.Prilepskoi. 2-e izd. M., 2010; s. 255. [in Russian]
17. Mozzanega B, Cosmi E. How do levonorgestrel-only emergency contraceptive pills prevent pregnancy? Some consideration. Gynecol Endocrinol 2011; 27(6): 439–42.
18. Hapanagama D, Glasier AF, Baird DT. The effects of peri-ovulatory administration of levonorgestrel on the menstrual cycle. Contraception 2001; 63: 123–9.
19. Noé G, Croxatto HB, Salvatierra AM et al. Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation. Contraception 2010; 81 (5): 414–20.
20. International Consortium for Emergency Contraception (ICEC), International Federatione of Gynecology & Obstetrics (FIGO). Statement on mechanism of action (October 2008).
21. International Consortium for Emergency Contraception (ICEC), International Federatione of Gynecology & Obstetrics (FIGO). Statement on mechanism of action (March 2011).
22. Durand M, Seppala M, Cravioto Mdel C et al. Late follicular phase administration of levonorgestrel as an emergency contraceptive changes the secretory pattern of glycodelin in serum and endometrium during the luteal phase of the menstrual cycle. Contraception. 2005; 71 (6): 451–7.
23. Palomino WA, Kohen P, Devoto L. A single midcycle dose of levonorgestrel similar to emergency contraceptive does not alter the expression of the L-selectin ligand or molecular markers of endometrial receptivity. Fertil Steril 2010; 94 (5): 1589–94.
24. Seppala M, Taylor RN, Koistinen H et al. Glycodelin: a major lipocalinprotein of the reproductive axis with diverse action sinc ellrecognition and differentiation. Endocr Rev 2002; 23: 401–30.
25. Brown SE, Mandelin E, Oehninger S et al. Endometrial glycodelin-A expression in the lutealphase of stimulated ovarian cycles. Fertil Steril 2000; 74: 130–3.
26. Rachmilewitz J, Riely GJ, Tykocinski ML. Placental protein 14 functions as a direct T-cell inhibitor. Cell Immunol 1999; 191: 26–33.
27. Oehninger S, Coddington CC, Hodgen GD et al. Factors affecting fertilization: endometrial placental protein 14 reduces the capacity of human spermatozoa o bind to the human zonapellucida. Fertil Steril 1995; 63: 377–83.
28. Meng C-X, Marions L, Bystrom B et al. Effects of oral and vaginal administration of levonorgestrel emergency contraception on markers of endometrial receptivity. Human Reproduction 2010; 25 (4): 874–83.
29. Spitz IM. Mifepristone: where do we come from and wh ere are we going? Clinical development over a quarter of a century. Contraception 2010; 82 (5): 442–52.
30. Wu S, Dong J, Cong J et al. Gestrinone compared with mifepristone for emergency contraception: a randomized controlled trial. Obstet Gynecol 2010; 115 (4): 740–4.
31. Esteve JL, García R, Breto A et al. Emergency contraception in Cuba with 10 mg of mifepristone. Eur J Contracept Reprod Health Care 2007; 12 (2): 162–7.
32. Harrison DJ, Mitroka JG. Defining reality: the potential role of pharmacists in assessing the impact of progesterone receptor modulators and misoprostol in reproductive health. Ann Pharmacother 2011; 45 (1): 115–9.
33. Mulac-Jericevic B, Conneely OM. Reproductive tissue selective actions of progesterone receptors. Reproduction 2004; 128: 139–46.
34. Wagner BL, Norris JD, Knotts TA et al. The nuclear corepressors NCoR and SMRT are key regulators of both ligand-and 8-bromo-cyclic AMP-dependent transcriptional activity of the human progesterone receptor. Mol Cell Biol 1998; 18: 1369–78.
35. Cervellati F, Pavan B, Lunghi L et al. Betamethasone, progesterone and RU-486 (mifepristone) exertsimilar effects on connexin expression in trophoblast-derived HTR-8/SV neocells. Reprod Fertil Dev 2011; 23 (2): 319–28.
36. Leminen R, Raivio T, Ranta S et al. Late follicular phase administration of mifepristone suppresses circulating leptin and FSH – mechanism(s) of action in emergency contraception? Eur J Endocrinol 2005; 152 (3): 411–8.
37. Marions L, Hultenby K, Lindell I et al. Emergency contraception with Mifepristone and Levonorgestrel: Mechanism of Action. Obstet Gynecol 2002; 100: 65–71.
38. Baird DT, Thong KJ, Hall C et al. Failure of oestrogeninduced luteinizing hormone surge in women treated with mifepristone (RU 486) every day for 30 days. Human Reproduction 1995; 10: 2270–6.
39. Watanobe H. Leptin directly acts within the hypothalamus to stimulate gonadotropin-releasing hormone secretion in vivo in rats. J Physiology 2002; 545: 255–68.
40. Licinio J, Negrao A, Mantzoros C et al. Synchronicity off requently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiolin healthy women. PNAS 1998; 95: 2541–6.
41. Newcomer JW, Selke G, Melson AK et al. Dose-dependent cortisol-induced increases in plasma leptin concentration in healthyhumans. Arch Gen Psychiatry 1998; 55: 995–1000.
42. Vicennati V, Vottero A, Friedman C et al. Hormonal regulation of interleukin-6 production in human adipocytes. Int J Obesity 2002; 26: 905–11.
43. Xiao BL, von Hertzen H, Zhao H et al. A randomized double-blind comparison of two single doses of mifepristone for emergency contraception. Hum Reprod 2002; 17: 3084–9.
44. Mori D, Ogino N, Yonezawa T et al. Anti-ovulatory effects of RU 486 and trilostane in volveimpaired cyclooxygenase-2 expression and mitotic activity of folliculargranulosa cells in rats. Prostaglandins Other Lipid Mediat 2011; 94 (3–4): 118–23.
45. Zhu HX, Zhang WW, Zhuang YL. Mifepristone as an anti-implantation contraceptive drug: roles in regulation of uterine natural killer cells during implantation phase. Am J Reprod Immunol 2009; 61 (1): 68–74.
46. Bygdeman M, Swahn ML. Progesterone receptor blockage. Effect on uterine contractility and early pregnancy. Contraception 1985; 32: 45–51.
47. Christow A , Sun X, Gemzell-Danielsson K. Effect of mifepristone and levonorgestrel on expression of steroid receptors in the human Fallopian tube. Mol Hum Reprod 2002; 8 (4): 333–40.
48. Gemzell-Danielsson K, Marions L. Mechanism of action of mifepristone and levonorgestrel when used for emergency contraception. Hum Reprod Update 2004; 10 (4): 341–8. DOI: 10.1093/humupd/dmh027.July-Aug 104341-8.8 2004
49. Bokström H, Norström A, Wiqvist N. Cervical mucus concentration of prostaglandins E2 and F2 alpha after pretreatment with mifepristone in the first trimester of pregnancy. Prostaglandins 1995; 49 (1): 41–8.
50. Li HWR, Lo SST, Ng EHY et al. Efficacy of ulipristal acetate for emergency contraception and its effect on the subsequent bleeding pattern when administered before or after ovulation. Human Reproduction 2016; 31 (6): 1200–7.
________________________________________________
1. ESHRE Capri Workshop Group Female contraception over 40. Human Reproduction Update 2009; 15 (6): 599–612.
2. American College of Obstetriciansand Gynecologist (ACOG) Statementon Contraceptive Methods 1998 A.
3. World Health Organization. Levonorgestrel for Emergency contraception. Geneva: WHO, 2005.
4. Haspels AA. Emergency Contraception: a Review. Contraception 1994; 50: 101–8.
5. Yuzpe AA, Turlow HJ, Ramzy I et al. Post-coital Contraception. Pilot Study. J Reprod Med 1974;13: 53–8.
6. Rukovodstvo po kontratseptsii. Pod red. V.N.Prilepskoi. 2-e izd., pererab. i dop. M.: MEDpress-inform, 2014. [in Russian]
7. Van Look PF, Von Hertzen H. Emergency Contraception. Br Med Bull 1993; 49: 158–70.
8. Swahn ML, Bygdeman M, Cekan S et al. The Effect of RU 486 Administred during the Early Luteal Phase on Bleeding Pattern, Hormonal Parameters and Endometrium. Hum Reprod 1990; 5: 402–8.
9. European Medicines Agency public assessment report (EPAR) Ella One 2009; Apr. EMEA/H/C 1027.
10. Emergency contraception. A guidline for service provision in Europe. December 2013. Europen Consortium for Emergency Contraception.
11. Durand M, del Carmen Cravioto M, Raymond EG et al. On the mechanisms of action of short-term levonorgestrel administration in emergency contraception. Contraception 2001; 64 (4): 227–34.
12. Hamoda H, Ashok PW, Stalder C et al. A randomized trial of mifepristone (10 mg) and levonorgestrel for emergency contraception. Obstet Gynecol 2004; 6: 1307–13.
13. Arowojolu AO, Okewole IA, Adekunle AO. Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians. Contraception 2002; 4: 269–73.
14. Turok DK. The copper IUD and emergency contraception. Contraception 2011; 84 (2): 205–6.
15. Julia E Kohn, Deborah L. Nucatola EC4U: results fr om a project integrating the copper IUC into emergency contraceptive care. Contraception 2016.
16. Rukovodstvo po ekstrennoi kontratseptsii. Pod red. V.N.Prilepskoi. 2-e izd. M., 2010; s. 255. [in Russian]
17. Mozzanega B, Cosmi E. How do levonorgestrel-only emergency contraceptive pills prevent pregnancy? Some consideration. Gynecol Endocrinol 2011; 27(6): 439–42.
18. Hapanagama D, Glasier AF, Baird DT. The effects of peri-ovulatory administration of levonorgestrel on the menstrual cycle. Contraception 2001; 63: 123–9.
19. Noé G, Croxatto HB, Salvatierra AM et al. Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation. Contraception 2010; 81 (5): 414–20.
20. International Consortium for Emergency Contraception (ICEC), International Federatione of Gynecology & Obstetrics (FIGO). Statement on mechanism of action (October 2008).
21. International Consortium for Emergency Contraception (ICEC), International Federatione of Gynecology & Obstetrics (FIGO). Statement on mechanism of action (March 2011).
22. Durand M, Seppala M, Cravioto Mdel C et al. Late follicular phase administration of levonorgestrel as an emergency contraceptive changes the secretory pattern of glycodelin in serum and endometrium during the luteal phase of the menstrual cycle. Contraception. 2005; 71 (6): 451–7.
23. Palomino WA, Kohen P, Devoto L. A single midcycle dose of levonorgestrel similar to emergency contraceptive does not alter the expression of the L-selectin ligand or molecular markers of endometrial receptivity. Fertil Steril 2010; 94 (5): 1589–94.
24. Seppala M, Taylor RN, Koistinen H et al. Glycodelin: a major lipocalinprotein of the reproductive axis with diverse action sinc ellrecognition and differentiation. Endocr Rev 2002; 23: 401–30.
25. Brown SE, Mandelin E, Oehninger S et al. Endometrial glycodelin-A expression in the lutealphase of stimulated ovarian cycles. Fertil Steril 2000; 74: 130–3.
26. Rachmilewitz J, Riely GJ, Tykocinski ML. Placental protein 14 functions as a direct T-cell inhibitor. Cell Immunol 1999; 191: 26–33.
27. Oehninger S, Coddington CC, Hodgen GD et al. Factors affecting fertilization: endometrial placental protein 14 reduces the capacity of human spermatozoa o bind to the human zonapellucida. Fertil Steril 1995; 63: 377–83.
28. Meng C-X, Marions L, Bystrom B et al. Effects of oral and vaginal administration of levonorgestrel emergency contraception on markers of endometrial receptivity. Human Reproduction 2010; 25 (4): 874–83.
29. Spitz IM. Mifepristone: where do we come from and wh ere are we going? Clinical development over a quarter of a century. Contraception 2010; 82 (5): 442–52.
30. Wu S, Dong J, Cong J et al. Gestrinone compared with mifepristone for emergency contraception: a randomized controlled trial. Obstet Gynecol 2010; 115 (4): 740–4.
31. Esteve JL, García R, Breto A et al. Emergency contraception in Cuba with 10 mg of mifepristone. Eur J Contracept Reprod Health Care 2007; 12 (2): 162–7.
32. Harrison DJ, Mitroka JG. Defining reality: the potential role of pharmacists in assessing the impact of progesterone receptor modulators and misoprostol in reproductive health. Ann Pharmacother 2011; 45 (1): 115–9.
33. Mulac-Jericevic B, Conneely OM. Reproductive tissue selective actions of progesterone receptors. Reproduction 2004; 128: 139–46.
34. Wagner BL, Norris JD, Knotts TA et al. The nuclear corepressors NCoR and SMRT are key regulators of both ligand-and 8-bromo-cyclic AMP-dependent transcriptional activity of the human progesterone receptor. Mol Cell Biol 1998; 18: 1369–78.
35. Cervellati F, Pavan B, Lunghi L et al. Betamethasone, progesterone and RU-486 (mifepristone) exertsimilar effects on connexin expression in trophoblast-derived HTR-8/SV neocells. Reprod Fertil Dev 2011; 23 (2): 319–28.
36. Leminen R, Raivio T, Ranta S et al. Late follicular phase administration of mifepristone suppresses circulating leptin and FSH – mechanism(s) of action in emergency contraception? Eur J Endocrinol 2005; 152 (3): 411–8.
37. Marions L, Hultenby K, Lindell I et al. Emergency contraception with Mifepristone and Levonorgestrel: Mechanism of Action. Obstet Gynecol 2002; 100: 65–71.
38. Baird DT, Thong KJ, Hall C et al. Failure of oestrogeninduced luteinizing hormone surge in women treated with mifepristone (RU 486) every day for 30 days. Human Reproduction 1995; 10: 2270–6.
39. Watanobe H. Leptin directly acts within the hypothalamus to stimulate gonadotropin-releasing hormone secretion in vivo in rats. J Physiology 2002; 545: 255–68.
40. Licinio J, Negrao A, Mantzoros C et al. Synchronicity off requently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiolin healthy women. PNAS 1998; 95: 2541–6.
41. Newcomer JW, Selke G, Melson AK et al. Dose-dependent cortisol-induced increases in plasma leptin concentration in healthyhumans. Arch Gen Psychiatry 1998; 55: 995–1000.
42. Vicennati V, Vottero A, Friedman C et al. Hormonal regulation of interleukin-6 production in human adipocytes. Int J Obesity 2002; 26: 905–11.
43. Xiao BL, von Hertzen H, Zhao H et al. A randomized double-blind comparison of two single doses of mifepristone for emergency contraception. Hum Reprod 2002; 17: 3084–9.
44. Mori D, Ogino N, Yonezawa T et al. Anti-ovulatory effects of RU 486 and trilostane in volveimpaired cyclooxygenase-2 expression and mitotic activity of folliculargranulosa cells in rats. Prostaglandins Other Lipid Mediat 2011; 94 (3–4): 118–23.
45. Zhu HX, Zhang WW, Zhuang YL. Mifepristone as an anti-implantation contraceptive drug: roles in regulation of uterine natural killer cells during implantation phase. Am J Reprod Immunol 2009; 61 (1): 68–74.
46. Bygdeman M, Swahn ML. Progesterone receptor blockage. Effect on uterine contractility and early pregnancy. Contraception 1985; 32: 45–51.
47. Christow A , Sun X, Gemzell-Danielsson K. Effect of mifepristone and levonorgestrel on expression of steroid receptors in the human Fallopian tube. Mol Hum Reprod 2002; 8 (4): 333–40.
48. Gemzell-Danielsson K, Marions L. Mechanism of action of mifepristone and levonorgestrel when used for emergency contraception. Hum Reprod Update 2004; 10 (4): 341–8. DOI: 10.1093/humupd/dmh027.July-Aug 104341-8.8 2004
49. Bokström H, Norström A, Wiqvist N. Cervical mucus concentration of prostaglandins E2 and F2 alpha after pretreatment with mifepristone in the first trimester of pregnancy. Prostaglandins 1995; 49 (1): 41–8.
50. Li HWR, Lo SST, Ng EHY et al. Efficacy of ulipristal acetate for emergency contraception and its effect on the subsequent bleeding pattern when administered before or after ovulation. Human Reproduction 2016; 31 (6): 1200–7.
Авторы
В.Н.Прилепская*, А.Н.Мгерян
ФГБУ «Научный центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова» Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4
*v_prilepskaya@oparina4.ru
________________________________________________
V.N.Prilepskaya*, A.N.Mgeryan
V.I.Kulakov Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4
*v_prilepskaya@oparina4.ru
.