Представленный обзор литературы посвящен изучению высокоселективного прогестагена последнего поколения – номегэстрола ацетата. Показаны его высокий антигонадотропный эффект, селективное влияние на прогестероновые рецепторы и низкое связывание с другими рецепторами, обусловливающие низкую частоту побочных эффектов. Не менее значимы высокая контрацептивная эффективность, приемлемость и отсутствие влияния на параметры гемостаза, липидный спектр крови, молочные железы. Ключевые слова: номегэстрола ацетат, прогестагены, гормональная контрацепция.
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This review of literature is devoted to the study of highly selective progestogen of the last generation – nomegestrol acetate. Showing its high antigonadotropic effect, as well as selective effect on the progesterone receptors, and low binding to other receptors, which results in a low incidence of side effects. No less significant are the high contraceptive efficacy, acceptability and lack of influence on the parameters of hemostasis, blood lipid profile, mammary glands. Key words: nomegestrol acetate, progestogens, hormonal contraception
1. Прилепская В.Н. XIII Всероссийский научный форум «Мать и дитя». Эволюция контрацепции: новый гормональный контрацептив (NOMAC/E2) – впервые в России. / Prilepskaia V.N. XIII Vserossiiskii nauchnyi forum «Mat' i ditia». Evoliutsiia kontratseptsii: novyi gormonal'nyi kontratseptiv (NOMAC/E2) – vpervye v Rossii. [in Russian]
2. Прилепская В.Н. Руководство по контрацепции. М., 2014. / Prilepskaia V.N. Rukovodstvo po kontratseptsii. M., 2014. [in Russian]
3. Прилепская В.Н., Довлетханова Э.Р., Абакарова П.Р. От аборта к сохранению репродуктивного здоровья: новое в контрацепции. Фарматека. 2013; 12: 46–9. / Prilepskaia V.N., Dovletkhanova E.R., Abakarova P.R. Ot aborta k sokhraneniiu reproduktivnogo zdorov'ia: novoe v kontratseptsii. Farmateka. 2013; 12: 46–9. [in Russian]
4. Sitruk-Ware R. Pharmocology of different progestagens:the special case of drospirenone. Climacteric 2005; 8 (Suppl. 3); 3–12.
5. Kuhl H. Pharmocology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005; 8 (Suppl. 1); 3–63.
6. Mueck AO, Sitruk-Ware R. Nomegestrol acetate, a novel progestogen for oral contraception. Steroids 2011; 76: 531–39.
7. Gaussem P, Alhenc-Gelas M, Thomas JL et al. Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17b-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomisedstudy. Thromb Haemost 2011; 105 (3): 560–67.
8. Basdevant A, Pelissier C, Conard J et al. Effects of nomegestrolacetate (5mg/d) on hormonal, metabolic and hemostatic parameters in premenopausal women. Contraception 1991; 44: 599–605.
9. Dorangeon P, Thomas JL, Choisy H et al. Effects of nomogestrol acetate on carbohydrate metabolism. Diabete Metab 1993; 19: 441–5.
10. Paris JM, Williams KJ, Hemsmeyer KR et al. Nomegestrol acetate and vascular reactivity: nonhuman primate experiments. Steroids 2000; 65: 621–7.
11. Chabbert-Buffet N, Christin-Maitre S, Ochsenbin E et al. Synergistic effect of 17b-estradiol and nomegestrol acetate used in a new monophasic oral contraceptive. In: 8th Congress of the European Society of Gynecology, 2009.
12. Lello S. Nomogestrol acetate: pharmacology, safety profile and therapeutic efficacy. Drugs 2010; 70: 541–59.
13. Duijkers I, Klipping CG, Korver T. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17b-oestradiol on ovarian function in comparison to a monophasic combined oral contraceptive containing drosperinone and ethinylestradiol. Eur J Contracept Reprod Health Care 2010; 15: 314–25.
14. Agren U, Antilla M, Rantala ML et al. Effects of an oral contraceptive containing nomogestrol acetate and 17 beta-estradiol on carbohydrate metabolism. The Hague, The Netherlands: European Society of Contraception and Reproductive Health, 2010.
15. Dinger JC, Heinemann LA, Juhl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation. Contraception 2007; 75: 344–54.
16. Doisneau- Sixou SF, Sergio CM, Carroll JS et al. Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells. Endocr Relat Cancer 2003; 10: 179–86.
17. Serfaty D, Christin Maitre S, Ochsenben E, Thomas J-L. Comparison of two regimens of new monophasic oral contraceptive combining 17 beta-estradiol and nomegestrol acetate. In XIX FIGO World Congress Gynecology and Obstretics, 2009.
18. Catherino WH, Jordan VC. Nomegestrol acetate, a clinically useful 19-norprogesterone derivative which lacks estrogenic activity. J Steroid Biochem Mol Biol 1995; 55: 239–46.
19. United Nations Department of Economic and Social Affairs, Population Division World contraceptive use 2011.
20. Jenset JT. Evaluation of a new estradiol oral contraceptive: estradiol valerate and dienogest. Expert Opin Pharmacother 2010; 11: 1147–57.
21. Sitruk-Ware R, Nath A. The use of newer progestins for contraception. Contraception 2010; 82: 410–7.
22. Gaussem P, Alhenc-Gelas M, Thomas JL et al. Haemostatic effects of a new combined oral contraceptive, nomogestrol acetate/17b-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomized study. Thromb Haemost 2011; 105: 560–7.
23. Kluft C, Endrikat J, Mulder SM et al. A prospective study on the effects on hemostasis of two oral contraceptives containing drosperinone in combination with either 30 or 20 microgethinyl estradiol and a reference containing desogestrel and 30 microgrethinyl estradiol. Contraception 2006; 73: 336–43.
24. Barbosa IC, Maia Jr H, Coutinho E et al. Effects of a single Silastic contraceptive implant containing nomegestrol acetate(Uniplant) on endometrial morphology and ovarian for 1 year. Contraception 2006; 74: 492–7.
25. Lemus AE, Santillan R, Damian-Matsumura P et al. In vitro metabolism of gestodene in target organs: formation of A-ring reduced derivates with oestrogenic activity. Eur J Pharmocol 2001; 417: 249–56.
26. Fraser DI, Padwick ML, Whitehead MI et al. The effects of the addition of nomegestrol acetate to post-menopausal oestrogen therapy. Maturitas 1989; 11: 21–34.
27. Shields-Botella J, Chetrite G, Meschi S et al. Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells. J Steroid Biochem Molecular Biol 2005; 93: 1–13.
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1. Prilepskaia V.N. XIII Vserossiiskii nauchnyi forum «Mat' i ditia». Evoliutsiia kontratseptsii: novyi gormonal'nyi kontratseptiv (NOMAC/E2) – vpervye v Rossii. [in Russian]
2. Prilepskaia V.N. Rukovodstvo po kontratseptsii. M., 2014. [in Russian]
3. Prilepskaia V.N., Dovletkhanova E.R., Abakarova P.R. Ot aborta k sokhraneniiu reproduktivnogo zdorov'ia: novoe v kontratseptsii. Farmateka. 2013; 12: 46–9. [in Russian]
4. Sitruk-Ware R. Pharmocology of different progestagens:the special case of drospirenone. Climacteric 2005; 8 (Suppl. 3); 3–12.
5. Kuhl H. Pharmocology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005; 8 (Suppl. 1); 3–63.
6. Mueck AO, Sitruk-Ware R. Nomegestrol acetate, a novel progestogen for oral contraception. Steroids 2011; 76: 531–39.
7. Gaussem P, Alhenc-Gelas M, Thomas JL et al. Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17b-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomisedstudy. Thromb Haemost 2011; 105 (3): 560–67.
8. Basdevant A, Pelissier C, Conard J et al. Effects of nomegestrolacetate (5mg/d) on hormonal, metabolic and hemostatic parameters in premenopausal women. Contraception 1991; 44: 599–605.
9. Dorangeon P, Thomas JL, Choisy H et al. Effects of nomogestrol acetate on carbohydrate metabolism. Diabete Metab 1993; 19: 441–5.
10. Paris JM, Williams KJ, Hemsmeyer KR et al. Nomegestrol acetate and vascular reactivity: nonhuman primate experiments. Steroids 2000; 65: 621–7.
11. Chabbert-Buffet N, Christin-Maitre S, Ochsenbin E et al. Synergistic effect of 17b-estradiol and nomegestrol acetate used in a new monophasic oral contraceptive. In: 8th Congress of the European Society of Gynecology, 2009.
12. Lello S. Nomogestrol acetate: pharmacology, safety profile and therapeutic efficacy. Drugs 2010; 70: 541–59.
13. Duijkers I, Klipping CG, Korver T. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17b-oestradiol on ovarian function in comparison to a monophasic combined oral contraceptive containing drosperinone and ethinylestradiol. Eur J Contracept Reprod Health Care 2010; 15: 314–25.
14. Agren U, Antilla M, Rantala ML et al. Effects of an oral contraceptive containing nomogestrol acetate and 17 beta-estradiol on carbohydrate metabolism. The Hague, The Netherlands: European Society of Contraception and Reproductive Health, 2010.
15. Dinger JC, Heinemann LA, Juhl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation. Contraception 2007; 75: 344–54.
16. Doisneau- Sixou SF, Sergio CM, Carroll JS et al. Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells. Endocr Relat Cancer 2003; 10: 179–86.
17. Serfaty D, Christin Maitre S, Ochsenben E, Thomas J-L. Comparison of two regimens of new monophasic oral contraceptive combining 17 beta-estradiol and nomegestrol acetate. In XIX FIGO World Congress Gynecology and Obstretics, 2009.
18. Catherino WH, Jordan VC. Nomegestrol acetate, a clinically useful 19-norprogesterone derivative which lacks estrogenic activity. J Steroid Biochem Mol Biol 1995; 55: 239–46.
19. United Nations Department of Economic and Social Affairs, Population Division World contraceptive use 2011.
20. Jenset JT. Evaluation of a new estradiol oral contraceptive: estradiol valerate and dienogest. Expert Opin Pharmacother 2010; 11: 1147–57.
21. Sitruk-Ware R, Nath A. The use of newer progestins for contraception. Contraception 2010; 82: 410–7.
22. Gaussem P, Alhenc-Gelas M, Thomas JL et al. Haemostatic effects of a new combined oral contraceptive, nomogestrol acetate/17b-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomized study. Thromb Haemost 2011; 105: 560–7.
23. Kluft C, Endrikat J, Mulder SM et al. A prospective study on the effects on hemostasis of two oral contraceptives containing drosperinone in combination with either 30 or 20 microgethinyl estradiol and a reference containing desogestrel and 30 microgrethinyl estradiol. Contraception 2006; 73: 336–43.
24. Barbosa IC, Maia Jr H, Coutinho E et al. Effects of a single Silastic contraceptive implant containing nomegestrol acetate(Uniplant) on endometrial morphology and ovarian for 1 year. Contraception 2006; 74: 492–7.
25. Lemus AE, Santillan R, Damian-Matsumura P et al. In vitro metabolism of gestodene in target organs: formation of A-ring reduced derivates with oestrogenic activity. Eur J Pharmocol 2001; 417: 249–56.
26. Fraser DI, Padwick ML, Whitehead MI et al. The effects of the addition of nomegestrol acetate to post-menopausal oestrogen therapy. Maturitas 1989; 11: 21–34.
27. Shields-Botella J, Chetrite G, Meschi S et al. Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells. J Steroid Biochem Molecular Biol 2005; 93: 1–13.
Авторы
В.Н.Прилепская*, А.Н.Мгерян, Е.А.Межевитинова
ФГБУ Научный центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4
*VPrilepskaya@mail.ru
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V.N.Prilepskaya*, A.N.Mgeryan, E.A.Mezhevitinova
V.I.Kulakov Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation.
1179974, Russian Federation, Moscow, ul. Akademika Oparina, d. 4
*VPrilepskaya@mail.ru