medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-5-40-45medsovet-6789Research ArticleРепродуктивное здоровье и ВРТReproductive health and ARTНизкодозированная внутриматочная контрацепция – инновационный подход к профилактике нежелательной беременностиLow-dose intrauterine contraception is an innovative approach to the prevention of unwanted pregnancyЧернухаГ. Е.ChernukhaG. E.

Чернуха Галина Евгеньевна, д.м.н., профессор, главный научный сотрудник отделения гинекологической эндокринологии 

117997, Москва, ул. Академика Опарина, д. 4

Galina E. Chernukha, Dr. Sci. (Med.), Professor, Chief Researcher of the Department of Gynecological Endocrinology

4, Academician Oparin St., Moscow, 117997

c-galina1@yandex.ruhttps://orcid.org/0000-0003-4566-4065ПронинаВ. А.ProninaV. A.

Пронина Вероника Алексеевна, врач – акушер-гинеколог, аспирант 

117997, Москва, ул. Академика Опарина, д. 4

Veronika A. Pronina, Obstetrician-Gynecologist, Postgraduate Student

4, Academician Oparin St., Moscow, 117997

ver22595@yandex.ruНаучный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. КулаковаРоссияKulakov National Medical Research Center of Obstetrics, Gynecology and PerinatologyRussian Federation202219042022054045Copyright © Чернуха Г.Е., Пронина В.А., 20222022Чернуха Г.Е., Пронина В.А.Chernukha G.E., Pronina V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6789

Обратимая контрацепция длительного действия Long-Acting Reversible Contraception (LARC) признана высокоэффективным и удобным в использовании методом предохранения от незапланированной беременности. Однако в реальной клинической практике сохраняется относительно низкий уровень использования LARC-методов, что может быть связано с неверными представлениями об  их контрацептивной надежности и  побочных эффектах как у  медицинских работников, так и у пациенток. Гормоносодержащие внутриматочные системы признаны одним из наиболее доступных методов контрацепции длительного действия. Они характеризуются очень низкой частотой неудач (менее 1%), т. к. их эффективность не зависит от приверженности пациентки к терапии. Анализ литературы показал, что среди женщин репродуктивного возраста наблюдается приверженность к низкодозированной контрацепции. Данная статья посвящена вопросу эффективности и безопасности низкодозированных левоноргестрел-содержащих внутриматочных систем, в частности, содержащей 19,5 мг прогестагена (ЛНГ-ВМС 19,5 мг). В обзоре приводятся данные о преимуществах данной внутриматочной системы в сравнении с ее аналогами. Несмотря на более низкое содержание левоноргестрела, ЛНГ-ВМС 12 (левоноргестрел-содержащая внутриматочная система Кайлина ЛНГ 19,5 мг со средней скоростью высвобождения ЛНГ 12 мкг / 24 ч in vivo в течение первого года использования) обладает высоким уровнем контрацептивной эффективности в течение пяти лет. Меньший диаметр трубки проводника внутриматочного устройства ассоциирован с более успешным и менее болезненным введением его в полость матки. Это может являться очевидным преимуществом для молодых нерожавших женщин. Кроме того, ЛНГ-ВМС оказывают в основном местное прогестагенное действие на эндометрий, в связи с чем наблюдается относительно небольшой риск развития системных эффектов. Таким образом, ЛНГ-ВМС 19,5 мг ассоциируется с благоприятным профилем контрацептивной надежности и безопасности независимо от возраста или репродуктивного статуса женщины, что было подтверждено результатами клинических испытаний и наблюдательных исследований.

 Long-acting reversible contraception (LARC) is recognized as a highly effective and convenient method for preventing unwanted pregnancy. However, in real clinical practice, the level of implementation of LARC remains relatively low, which, presumably, may be related to misconceptions about their contraceptive efficacy and side effects among health professionals and patients. One method of long-acting reversible contraception is the intrauterine device. Hormone-containing intrauterine systems are recognized as one of the most affordable contraceptive methods, characterized by a very low failure rate (less than 1%), which does not depend on the patient’s compliance. A review of the literature focuses on the efficacy and safety of a low-dose levonorgestrelcontaining intrauterine system containing 19.5 mg of levonorgestrel (LNG-IUD 12). We present data on the advantages of this intrauterine system in comparison with its counterparts. Analysis of the literature has shown that adherence to low-dose contraception is observed among women of reproductive age. The smaller diameter of the guide tube is associated with a more successful and less painful insertion of the device into the uterine cavity. This may be an obvious advantage for young, nulliparous women. In addition, the LNG-IUD has a predominantly local progestogenic effect on the endometrium, so there is a relatively low development of systemic effects. Despite its lower levonorgestrel content, the LNG IUD 12 (Kyleena LNG 19.5 mg, levonorge strel-releasing intrauterine system with an average LNG release of 12 µg/24 h in vivo over the first year of use) has a high level of contraceptive efficacy. Thus, LNG-IUD 12 is associated with a favorable efficacy and safety profile regardless of a woman’s age or parity, which has been confirmed by the results of clinical trials.

гормональная контрацепцияобратимая контрацепция длительного действиявнутриматочная контрацепциянизкодозированная левоноргестрел-содержащая внутриматочная системаЛНГ-ВМС 12hormonal contraceptionlong-acting reversible contraceptionintrauterine contraceptionlow-dose levonorgestrel intrauterine deviceLNG-IUD 12ReferencesWu J.P., Moniz M.H., Ursu A.N. Long-acting Reversible Contraception – Highly Efficacious, Safe, and Underutilized. JAMA. 2018;320(4):397–398. https://doi.org/10.1001/jama.2018.8877.Wu J.P., Moniz M.H., Ursu A.N. Long-acting Reversible Contraception – Highly Efficacious, Safe, and Underutilized. JAMA. 2018;320(4):397–398. https://doi.org/10.1001/jama.2018.8877.Kavanaugh M.L., Jerman J. Contraceptive method use in the United States: trends and characteristics between 2008, 2012 and 2014. Contraception. 2018;97(1):14–21. https://doi.org/10.1016/j.contraception.2017.10.003.Kavanaugh M.L., Jerman J. Contraceptive method use in the United States: trends and characteristics between 2008, 2012 and 2014. Contraception. 2018;97(1):14–21. https://doi.org/10.1016/j.contraception.2017.10.003.Beshar I., So J., Chelvakumar M., Cahill E.P., Shaw K.A., Shaw J.G. Socioeconomic differences persist in use of permanent vs long-acting reversible contraception: An analysis of the National Survey of Family Growth, 2006 to 2010 vs 2015 to 2017. Contraception. 2021;103(4):246–254. https://doi.org/10.1016/j.contraception.2020.12.008.Beshar I., So J., Chelvakumar M., Cahill E.P., Shaw K.A., Shaw J.G. Socioeconomic differences persist in use of permanent vs long-acting reversible contraception: An analysis of the National Survey of Family Growth, 2006 to 2010 vs 2015 to 2017. Contraception. 2021;103(4):246–254. https://doi.org/10.1016/j.contraception.2020.12.008.Lindh I., Skjeldestad F.E., Gemzell-Danielsson K., Heikinheimo O., Hognert H., Milsom I., Lidegaard Ø. Contraceptive use in the nordic countries. Acta Obstet Gynecol Scand. 2017;96(1):19–28. https://doi.org/10.1111/aogs.13055.Lindh I., Skjeldestad F.E., Gemzell-Danielsson K., Heikinheimo O., Hognert H., Milsom I., Lidegaard Ø. Contraceptive use in the nordic countries. Acta Obstet Gynecol Scand. 2017;96(1):19–28. https://doi.org/10.1111/aogs.13055.Baron M.M., Potter B., Schrager S. A Review of Long-Acting Reversible Contraception Methods and Barriers to Their Use. WMJ. 2018;117(4):156–159. Available at: https://pubmed.ncbi.nlm.nih.gov/30407765.Baron M.M., Potter B., Schrager S. A Review of Long-Acting Reversible Contraception Methods and Barriers to Their Use. WMJ. 2018;117(4):156–159. Available at: https://pubmed.ncbi.nlm.nih.gov/30407765.Thiery M. Pioneers of the intrauterine device. Eur J Contracept Reprod Health Care. 1997;2(1):15–23. https://doi.org/10.1080/13625189709049930.Thiery M. Pioneers of the intrauterine device. Eur J Contracept Reprod Health Care. 1997;2(1):15–23. https://doi.org/10.1080/13625189709049930.Thiery M. Intrauterine contraception: from silver ring to intrauterine contraceptive implant. Eur J Obstet Gynecol Reprod Biol. 2000;90(2):145–152. https://doi.org/10.1016/s0301-2115(00)00262-1.Thiery M. Intrauterine contraception: from silver ring to intrauterine contraceptive implant. Eur J Obstet Gynecol Reprod Biol. 2000;90(2):145–152. https://doi.org/10.1016/s0301-2115(00)00262-1.Luukkainen T., Pakarinen P., Toivonen J. Progestin-Releasing Intrauterine Systems. Semin Reprod Med. 2001;19(04):355–364. https://doi.org/10.1055/s-2001-18643.Luukkainen T., Pakarinen P., Toivonen J. Progestin-Releasing Intrauterine Systems. Semin Reprod Med. 2001;19(04):355–364. https://doi.org/10.1055/s-2001-18643.Wadsworth P.F., Heywood R., Allen D.G., Hossack D.J., Sortwell R.J., Walton R.M. Treatment of rhesus monkeys (Macaca mulatta) with intrauterine devices loaded with levonorgestrel. Contraception. 1979;20(6):559–567. https://doi.org/10.1016/s0010-7824(79)80035-9.Wadsworth P.F., Heywood R., Allen D.G., Hossack D.J., Sortwell R.J., Walton R.M. Treatment of rhesus monkeys (Macaca mulatta) with intrauterine devices loaded with levonorgestrel. Contraception. 1979;20(6):559–567. https://doi.org/10.1016/s0010-7824(79)80035-9.Nilsson C.G., Lähteenmäki P., Luukkainen T. Patterns of ovulation and bleeding with a low levonorgestrel-releasing intrauterine device. Contraception. 1980;21(2):155–64. https://doi.org/10.1016/0010-7824(80)90127-4.Nilsson C.G., Lähteenmäki P., Luukkainen T. Patterns of ovulation and bleeding with a low levonorgestrel-releasing intrauterine device. Contraception. 1980;21(2):155–64. https://doi.org/10.1016/0010-7824(80)90127-4.Luukkainen T., Allonen H., Haukkamaa M., Lähteenmäki P., Nilsson C.G., Toivonen J. Five years’ experience with levonorgestrel-releasing IUDs. Contraception. 1986;33(2):139–148. https://doi.org/10.1016/0010-7824(86)90080-6.Luukkainen T., Allonen H., Haukkamaa M., Lähteenmäki P., Nilsson C.G., Toivonen J. Five years’ experience with levonorgestrel-releasing IUDs. Contraception. 1986;33(2):139–148. https://doi.org/10.1016/0010-7824(86)90080-6.Reinecke I., Hofmann B., Mesic E., Drenth H.-J., Garmann D. An Integrated Population Pharmacokinetic Analysis to Characterize Levonorgestrel Pharmacokinetics After Different Administration Routes. J Clin Pharmacol. 2018;58(12):1639–1654. https://doi.org/10.1002/jcph.1288.Reinecke I., Hofmann B., Mesic E., Drenth H.-J., Garmann D. An Integrated Population Pharmacokinetic Analysis to Characterize Levonorgestrel Pharmacokinetics After Different Administration Routes. J Clin Pharmacol. 2018;58(12):1639–1654. https://doi.org/10.1002/jcph.1288.Hofmann B.M., Apter D., Bitzer J., Reinecke I., Serrani M., Höchel J., Merz M. Comparative pharmacokinetic analysis of levonorgestrel-releasing intrauterine systems and levonorgestrel-containing contraceptives with oral or subdermal administration route. Eur J Contracept Reprod Health Care. 2020;25(6):417–426. https://doi.org/10.1080/13625187.2020.1815008.Hofmann B.M., Apter D., Bitzer J., Reinecke I., Serrani M., Höchel J., Merz M. Comparative pharmacokinetic analysis of levonorgestrel-releasing intrauterine systems and levonorgestrel-containing contraceptives with oral or subdermal administration route. Eur J Contracept Reprod Health Care. 2020;25(6):417–426. https://doi.org/10.1080/13625187.2020.1815008.Stanford J.B., Mikolajczyk R.T. Mechanisms of action of intrauterine devices: update and estimation of postfertilization effects. Am J Obstet Gynecol. 2002;187(6):1699–1708. https://doi.org/10.1067/mob.2002.128091.Stanford J.B., Mikolajczyk R.T. Mechanisms of action of intrauterine devices: update and estimation of postfertilization effects. Am J Obstet Gynecol. 2002;187(6):1699–1708. https://doi.org/10.1067/mob.2002.128091.Attia A.M., Ibrahim M.M., Abou-Setta A.M. Role of the levonorgestrel intrauterine system in effective contraception. Patient Prefer Adherence. 2013;7:777–785. https://doi.org/10.2147/PPA.S36948.Attia A.M., Ibrahim M.M., Abou-Setta A.M. Role of the levonorgestrel intrauterine system in effective contraception. Patient Prefer Adherence. 2013;7:777–785. https://doi.org/10.2147/PPA.S36948.Apter D., Gemzell-Danielsson K., Hauck B., Rosen K., Zurth C. Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems and effects on ovulation rate and cervical function: pooled analyses of phase II and III studies. Fertil Steril. 2014;101(6):1656–1662.e1–4. https://doi.org/10.1016/j.fertnstert.2014.03.004.Apter D., Gemzell-Danielsson K., Hauck B., Rosen K., Zurth C. Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems and effects on ovulation rate and cervical function: pooled analyses of phase II and III studies. Fertil Steril. 2014;101(6):1656–1662.e1–4. https://doi.org/10.1016/j.fertnstert.2014.03.004.Nelson A., Apter D., Hauck B., Schmelter T., Rybowski S., Rosen K., GemzellDanielsson K. Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems. Obstet Gynecol. 2013;122(6):1205–1213. https://doi.org/10.1097/aog.0000000000000019.Nelson A., Apter D., Hauck B., Schmelter T., Rybowski S., Rosen K., GemzellDanielsson K. Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems. Obstet Gynecol. 2013;122(6):1205–1213. https://doi.org/10.1097/aog.0000000000000019.Gemzell-Danielsson K., Apter D., Dermout S., Faustmann T., Rosen K., Schmelter T. et al. Evaluation of a new, low-dose levonorgestrel intrauterine contraceptive system over 5 years of use. Eur J Obstet Gynecol Reprod Biol. 2017;210:22–28. https://doi.org/10.1016/j.ejogrb.2016.11.022.Gemzell-Danielsson K., Apter D., Dermout S., Faustmann T., Rosen K., Schmelter T. et al. Evaluation of a new, low-dose levonorgestrel intrauterine contraceptive system over 5 years of use. Eur J Obstet Gynecol Reprod Biol. 2017;210:22–28. https://doi.org/10.1016/j.ejogrb.2016.11.022.Gemzell-Danielsson K., Schellschmidt I., Apter D. A randomized, phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena. Fertil Steril. 2012;97(3):616–622.e1–3. https://doi.org/10.1016/j.fertnstert.2011.12.003.Gemzell-Danielsson K., Schellschmidt I., Apter D. A randomized, phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena. Fertil Steril. 2012;97(3):616–622.e1–3. https://doi.org/10.1016/j.fertnstert.2011.12.003.Beckert V., Aqua K., Bechtel C., Cornago S., Kallner K.H., Schulze A. et al. Insertion experience of women and health care professionals in the Kyleena® Satisfaction Study. Eur J Contracept Reprod Health Care. 2020;25(3):182–189. https://doi.org/10.1080/13625187.2020.1736547.Beckert V., Aqua K., Bechtel C., Cornago S., Kallner K.H., Schulze A. et al. Insertion experience of women and health care professionals in the Kyleena® Satisfaction Study. Eur J Contracept Reprod Health Care. 2020;25(3):182–189. https://doi.org/10.1080/13625187.2020.1736547.Stovall W.D., Aqua K., Römer T., Donders G., Sørdal T., Hauck B. et al. Satisfaction and continuation with LNG-IUS 12: findings from the realworld kyleena® satisfaction study. Eur J Contracept Reprod Health Care. 2021;26(6):462–472. https://doi.org/10.1080/13625187.2021.1975268.Stovall W.D., Aqua K., Römer T., Donders G., Sørdal T., Hauck B. et al. Satisfaction and continuation with LNG-IUS 12: findings from the realworld kyleena® satisfaction study. Eur J Contracept Reprod Health Care. 2021;26(6):462–472. https://doi.org/10.1080/13625187.2021.1975268.

The authors declare that there are no conflicts of interest present.