pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2026-14-1-4-17pmedpharm-1809Research ArticleОБЗОРЫREVIEWФармакотерапия эндометриоза: баланс безопасности, эффективности и приверженности к лечениюPharmacotherapy of Endometriosis: Balancing of Safety, Efficacy, and Adherence to Treatmenthttps://orcid.org/0000-0002-0258-4092ПетровВ. И.PetrovV. I.

доктор медицинских наук, профессор, заведующий кафедрой клинической фармакологии и интенсивной терапии, ФГБОУ ВО ВолгГМУ Минздрава России; академик РАН, главный внештатный специалист — клинический фармаколог Министерства здравоохранения РФ; заслуженный деятель науки РФ; заслуженный врач РФ.

Россия, 400066, г. Волгоград, пл. Павших Борцов, д. 1.

Doctor of Sciences (Medicine), Professor, Head of the Department of Clinical Pharmacology and Intensive Care of the Volgograd State Medical University; Chief freelance specialist — Clinical Pharmacologist of the Ministry of Health of the Russian Federation; Honored Scientist of the Russian Federation; Honored Doctor of the Russian Federation; Academician of the Russian Academy of Sciences. 

1 Pavshikh Bortsov Sq., Volgograd, Russia, 400066.

 

brain@sprintnet.ruhttps://orcid.org/0000-0002-2717-8218КулаковаИ. С.KulakovaI. S.

соискатель кафедры клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России, врач акушер-гинеколог клиники «Дочки-матери». 

1. Россия, 400066, г. Волгоград, пл. Павших Борцов, д. 1.

2. Россия, 400087, г Волгоград, ул. Невская, д. 2.

applicant of the Department of Clinical Pharmacology and Intensive Care of the Volgograd State Medical University; obstetrician-gynecologist, Dochki-Materi Clinics (Volgograd). 

1. 1 Pavshikh Bortsov Sq., Volgograd, Russia, 400066.

2. 2 Nevskaya Str., Volgograd, Russia, 400087.

iraida97@mail.ruhttps://orcid.org/0000-0002-6565-2566ГорбатенкоВ. С.GorbatenkoV. S.

кандидат медицинских наук, доцент кафедры клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России. 

Россия, 400066, г. Волгоград, пл. Павших Борцов, д. 1.

 

Candidate of Sciences (Medicine), Assistant Professor of the Department of Clinical Pharmacology and Intensive Care of the Volgograd State Medical University. 

1 Pavshikh Bortsov Sq., Volgograd, Russia, 400066

 

vlad30.03@mail.ruhttps://orcid.org/0000-0002-7311-4549ШаталоваО. В.ShatalovaO. V.

доктор медицинских наук, профессор кафедры клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России.

Россия, 400066, г. Волгоград, пл. Павших Борцов, д. 1.

Doctor of Sciences (Medicine), Professor of the Department of Clinical Pharmacology and Intensive Care of the Volgograd State Medical University. 

1 Pavshikh Bortsov Sq., Volgograd, Russia, 400066

 

shov_med@mail.ruhttps://orcid.org/0009-0007-1579-5765БезугловИ. Д.BezuglovI. D.

студент 6 курса лечебного факультета ФГБОУ ВО ВолгГМУ Минздрава России. 

Россия, 400066, г. Волгоград, пл. Павших Борцов, д. 1.

 

6th year student of the Faculty of Medicine of the Volgograd State Medical University. 

1 Pavshikh Bortsov Sq., Volgograd, Russia, 400066

 

i.bezuglov.d@bk.ruhttps://orcid.org/0009-0000-1140-5124ИгнатоваА. С.IgnatovaA. S.

студентка 6 курса леченого факультета ФГБОУ ВО ВолгГМУ Минздрава России. 

Россия, 400066, г. Волгоград, пл. Павших Борцов, д. 1.

6th year student of the Faculty of Medicine of the Volgograd State Medical University. 

1 Pavshikh Bortsov Sq., Volgograd, Russia, 400066

 

9281459863@mail.ru1 Федеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияVolgograd State Medical UniversityRussian Federation1. Федеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации. 2. Общество с ограниченной ответственностью «ДОЧКИ-МАТЕРИ».Россия1. Volgograd State Medical University. 2. Dochki-materi Clinics.Russian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияVolgograd State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации.РоссияVolgograd State Medical UniversityRussian Federation202622032026141417Copyright © Петров В.И., Кулакова И.С., Горбатенко В.С., Шаталова О.В., Безуглов И.Д., Игнатова А.С., 20262026Петров В.И., Кулакова И.С., Горбатенко В.С., Шаталова О.В., Безуглов И.Д., Игнатова А.С.Petrov V.I., Kulakova I.S., Gorbatenko V.S., Shatalova O.V., Bezuglov I.D., Ignatova A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/1809Цель

Цель. Проведение комплексного анализа клинико-фармакологической эффективности прогестинов (дидрогестерона, диеногеста и норэтистерона ацетата) для терапии эндометриоза путем систематизации данных об их фармакодинамических, фармакокинетических характеристиках и профиле безопасности для оптимизации выбора персонализированной терапевтической стратегии.

Материалы и методы

Материалы и методы. Поиск литературы проводили среди рандомизированных контролируемых исследований (РКИ), когортных исследований и метаанализов за период с 1958 по 2025 гг. в базах данных PubMed, Cochrane Library и eLibrary.ru.

Результаты

Результаты. Установлено, что диеногест, дидрогестерон и норэтистерона ацетат демонстрируют сопоставимую эффективность в снижении интенсивности эндометриоз-ассоциированной тазовой боли. Диеногест показал эффективность, сравнимую с агонистами гонадотропин-рилизинг-гормона, но с лучшим профилем переносимости. Дидрогестерон проявлял наилучший профиль безопасности с минимальным влиянием на метаболические параметры. Норэтистерон ацетат показал сопоставимую с диеногестом эффективность, но с более выраженными андрогенными эффектами. Определены ключевые фармакологические особенности, влияющие на профиль безопасности препаратов, а также обоснована необходимость персонализированного подхода к выбору терапии. Основным ограничением является недостаточное количество прямых сравнительных исследований различных прогестинов.

Заключение

Заключение. Все рассмотренные прогестины являются эффективными средствами терапии эндометриоза, однако имеют различные профили безопасности, что предопределяет необходимость индивидуального выбора препарата с учетом особенностей пациентки и сопутствующей патологии. Перспективными направлениями будущих исследований являются проведение крупных многоцентровых РКИ, разработка алгоритмов персонализированного выбора терапии и изучение долгосрочных эффектов лечения.

The aim

The aim. To conduct a comprehensive analysis of the clinical and pharmacological efficacy of progestins (dydrogesterone, dienogest, and norethisterone acetate) for the treatment of endometriosis by systematizing data on their pharmacodynamic, pharmacokinetic characteristics, and safety profile to optimize the selection of a personalized therapeutic strategy.

Materials and methods

Materials and methods. The search of the literature was conducted regarding randomized controlled trials (RCTs), cohort studies, and meta-analyses for the period from 1958 to 2025 from the PubMed, Cochrane Library, and eLibrary.ru databases.

Results

Results. It was found that dienogest, dydrogesterone, and norethisterone acetate demonsrates comparable efficacy in reducing the intensity of endometriosis-associated pelvic pain. Dienogest showed efficacy comparable to gonadotropin-releasing hormone agonists with a better tolerability profile. Dydrogesterone exhibited the best safety profile with minimal impact on metabolic parameters. Norethisterone acetate showed efficacy comparable to dienogest, but with more pronounced androgenic effects. Key pharmacological features affecting the safety profile of drugs were identified, and the need for a personalized approach to the choice of therapy was justified. The main limitation is the insufficient number of direct comparative studies of various progestins.

Conclusion

Conclusion. All the progestins considered are effective treatments for endometriosis, but have different safety profiles, which determines the need for individual drug selection, taking into account the patient’s characteristics and concomitant pathology. Promising areas for future research include conducting large multi-center RCTs, developing algorithms for personalized therapy selection, and studying the long-term effects of treatment.

эндометриозпрогестиныдиеногестдидрогестероннорэтистерона ацетатагонисты гонадотропин-рилизинг-гормонакомбинированные оральные контрацептивыхроническая тазовая больклиническая эффективностьбезопасностьendometriosisprogestinsdienogestdydrogesteronenorethisterone acetategonadotropin-releasing hormone agonistscombined oral contraceptiveschronic pelvic painclinical efficacysafetyДанная работа не имела финансовой поддержки от сторонних организаций.This study did not have financial support from third-party organizations.ReferencesMissmer S.A., Tu F.F., Agarwal S.K., Chapron C., Soliman A.M., Chiuve S., Eichner S., Flores-Caldera I., Horne A.W., Kimball A.B., Laufer M.R., Leyland N., Singh S.S., Taylor H.S., As-Sanie S. Impact of endometriosis on life-course potential: a narrative review // Int J Gen Med. – 2021. – Vol. 14. – P. 9–25. DOI: 10.2147/IJGM.S261139Missmer SA, Tu FF, Agarwal SK, Chapron C, Soliman AM, Chiuve S, Eichner S, Flores-Caldera I, Horne AW, Kimball AB, Laufer MR, Leyland N, Singh SS, Taylor HS, As-Sanie S. Impact of Endometriosis on Life-Course Potential: A Narrative Review. Int J Gen Med. 2021;14:9–25. DOI: 10.2147/IJGM.S261139Taylor H.S., Kotlyar A.M., Flores V.A. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations // Lancet. – 2021. – Vol. 397, No. 10276. – P. 839–852. DOI: 10.1016/S0140-6736(21)00389-5Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;397(10276):839–852. DOI: 10.1016/S0140-6736(21)00389-5Ghiasi M., Kulkarni M.T., Missmer S.A. Is endometriosis more common and more severe than it was 30 years ago? // J Minim Invasive Gynecol. – 2020. – Vol. 27, No. 2. – P. 452–461. DOI: 10.1016/j.jmig.2019.11.018Ghiasi M, Kulkarni MT, Missmer SA. Is Endometriosis More Common and More Severe Than It Was 30 Years Ago? J Minim Invasive Gynecol. 2020;27(2):452–461. DOI: 10.1016/j.jmig.2019.11.018Улумбекова Г.Э., Худова И.Ю. Оценка демографического, социального и экономического эффекта применения гормональной терапии при эндометриозе и аномальных маточных кровотечениях // ОРГЗДРАВ: новости, мнения, обучение. Вестник ВШОУЗ. – 2022. – Т. 8, № 1. – С. 82–113. DOI: 10.33029/2411-8621-2022-8-1-82-113 EDN: VCNEQYUlumbekova GE, Khudova IYu. Demographic, social and economic effects of hormonal therapy in endometriosis and abnormal uterine bleeding. HEALTHCARE MANAGEMENT: News, Views, Education. Bulletin of VSHOUZ. 2022; 8 (1): 82–113. DOI: 10.33029/2411-8621-2022-8-1-82-113 EDN: VCNEQYЯрмолинская М.И., Сейидова Ч.И., Пьянкова В.О. Современная тактика назначения медикаментозной терапии генитального эндометриоза // Акушерство и гинекология. – 2021. – Т. 4. – С. 55–62. DOI: 10.18565/aig.2021.4.55-62 EDN: BCPQJTYarmolinskaya MI, Seyidova ChI, Pyankova VO. Modern tactics in prescribing drug therapy for genital endometriosis. Obstetrics and Gynecology. 2021;4:55–62. DOI: 10.18565/aig.2021.4.55-62 EDN: BCPQJTAlonso A., Gunther K., Maheux-Lacroix S., Abbott J. Medical management of endometriosis // Curr Opin Obstet Gynecol. – 2024. – Vol. 36, No. 5. – P. 353–361. DOI: 10.1097/GCO.0000000000000983Alonso A, Gunther K, Maheux-Lacroix S, Abbott J. Medical management of endometriosis. Curr Opin Obstet Gynecol. 2024;36(5):353–361. DOI: 10.1097/GCO.0000000000000983Carneiro M.M. Deciding on the appropriate pharmacotherapy for the treatment of endometriosis // Expert Opin Pharmacother. – 2023. – Vol. 24, No. 1. – P. 1–5. DOI: 10.1080/14656566.2022.2113383Carneiro MM. Deciding on the appropriate pharmacotherapy for the treatment of endometriosis. Expert Opin Pharmacother. 2023;24(1):1–5. DOI: 10.1080/14656566.2022.2113383Mitchell J.B., Chetty S., Kathrada F. Progestins in the symptomatic management of endometriosis: a meta-analysis on their effectiveness and safety // BMC Womens Health. – 2022. – Vol. 22, No. 1. – P. 526. DOI: 10.1186/s12905-022-02122-0Mitchell JB, Chetty S, Kathrada F. Progestins in the symptomatic management of endometriosis: a meta-analysis on their effectiveness and safety. BMC Womens Health. 2022;22(1):526. DOI: 10.1186/s12905-022-02122-0Gezer A., Oral E. Progestin therapy in endometriosis // Womens Health (Lond). – 2015. – Vol. 11, No. 5. – P. 643–652. DOI: 10.2217/whe.15.42Gezer A, Oral E. Progestin therapy in endometriosis. Womens Health (Lond). 2015;11(5):643–652. DOI: 10.2217/whe.15.42Flyckt R., Kim S., Falcone T. Surgical management of endometriosis in patients with chronic pelvic pain // Semin Reprod Med. – 2017. – Vol. 35, No. 01. – P. 54–64. DOI: 10.1055/s-0036-1597306Flyckt R, Kim S, Falcone T. Surgical Management of Endometriosis in Patients with Chronic Pelvic Pain. Semin Reprod Med. 2017;35(1):54–64. DOI: 10.1055/s-0036-1597306Razzi S., Luisi S., Ferretti C., Calonaci F., Gabbanini M., Mazzini M., Petraglia F. Use of a progestogen only preparation containing desogestrel in the treatment of recurrent pelvic pain after conservative surgery for endometriosis // Eur J Obstet Gynecol Reprod Biol. – 2007. – Vol. 135, No. 2. – P. 188–190. DOI: 10.1016/j.ejogrb.2006.08.002Razzi S, Luisi S, Ferretti C, Calonaci F, Gabbanini M, Mazzini M, Petraglia F. Use of a progestogen only preparation containing desogestrel in the treatment of recurrent pelvic pain after conservative surgery for endometriosis. Eur J Obstet Gynecol Reprod Biol. 2007;135(2):188–190. DOI: 10.1016/j.ejogrb.2006.08.002Ярмолинская М.И., Адамян Л.В. Гормональные контрацептивы и эндометриоз: современный взгляд на проблему // Проблемы репродукции. – 2020. – Т. 26, № 3. – С. 39–45. DOI: 10.17116/repro20202603139Yarmolinskaya MI, Adamyan LV. Hormonal contraceptives and endometriosis: modern view on the problem. Russian Journal of Human Reproduction. 2020;26(3):39–45. DOI: 10.17116/repro20202603139Kiesel L., Sourouni M. Diagnosis of endometriosis in the 21st century // Climacteric. – 2019. – Vol. 22, No. 3. – P. 296–302. DOI: 10.1080/13697137.2019.1578743Kiesel L, Sourouni M. Diagnosis of endometriosis in the 21st century. Climacteric. 2019;22(3):296–302. DOI: 10.1080/13697137.2019.1578743D’Alterio M.N., Saponara S., Agus M., Lagana A.S., Noventa M., Loi E.S., Feki A., Angioni S. Medical and surgical interventions to improve the quality of life for endometriosis patients: a systematic review // Gynecological Surgery. – 2021. – Vol. 18, No. 1. – P. 1–14. DOI: 10.1186/s10397-021-01096-5D’Alterio MN, Saponara S, Agus M, Lagana AS, Noventa M, Loi ES, Feki A, Angioni S. Medical and surgical interventions to improve the quality of life for endometriosis patients: a systematic review. Gynecological Surgery. 2021;18(1):1–14. DOI: 10.1186/s10397-021-01096-5Сухих Г.Т., Серов В.Н., Адамян Л.В., Баранов И.И., Беженарь В.Ф., Габидуллина Р.И., Дубровина С.О., Козаченко А.В., Подзолкова Н.М., Сметник А.А., Тапильская Н.И., Уварова Е.В., Ших Е.В., Ярмолинская М.И. Алгоритмы ведения пациенток с эндометриозом: согласованная позиция экспертов Российского общества акушеров-гинекологов // Акушерство и гинекология. – 2023. – Т. 5. – С. 159–176. DOI: 10.18565/aig.2023.132Sukhikh GT, Serov VN, Adamyan LV, Baranov II, Bezhenar VF, Gabidullina RI, Dubrovina SO, Kozachenko AV, Podzolkova NM, Smetnik AA, Tapilskaya NI, Uvarova EV, Shikh EV, Yarmolinskaya MI. Algorithms for the management of patients with endometriosis: an agreed position of experts from the Russian Society of Obstetricians and Gynecologists. Obstetrics and Gynecology. 2023;(5):159–176. DOI: 10.18565/aig.2023.132Федотчева Т.А., Шимановский Н.Л. Роль гестагенов в лечении эндометриоза // Проблемы эндокринологии. – 2018. – Т. 64, № 1. – С. 54–61. DOI: 10.14341/probl8742Fedotcheva TA, Shimanovskiy NL. Gestagens in the treatment of endometriosis. Problems of Endocrinology. 2018;64(1):54–61. DOI: 10.14341/probl8742Rižner T.L., Brožič P., Doucette C., Turek-Etienne T., Muller-Vieira U., Sonneveld E., van der Burg B., Böcker C., Husen B. Selectivity and potency of the retroprogesterone dydrogesterone in vitro // Steroids. – 2011. – Vol. 76, No. 6. – P. 607–615. DOI: 10.1016/j.steroids.2011.02.043Rižner TL, Brožič P, Doucette C, Turek-Etienne T, Müller-Vieira U, Sonneveld E, van der Burg B, Böcker C, Husen B. Selectivity and potency of the retroprogesterone dydrogesterone in vitro. Steroids. 2011;76(6):607–615. DOI: 10.1016/j.steroids.2011.02.043Colombo D., Ferraboschi P., Prestileo P., Toma L. A comparative molecular modeling study of dydrogesterone with other progestational agents through theoretical calculations and nuclear magnetic resonance spectroscopy // J Steroid Biochem Mol Biol. – 2006. – Vol. 98, No. 1. – P. 56–62. DOI: 10.1016/j.jsbmb.2005.07.009Colombo D, Ferraboschi P, Prestileo P, Toma L. A comparative molecular modeling study of dydrogesterone with other progestational agents through theoretical calculations and nuclear magnetic resonance spectroscopy. J Steroid Biochem Mol Biol. 2006 Jan;98(1):56-62. DOI: 10.1016/j.jsbmb.2005.07.009Сергеев П.В., Шимановский Н.Л. Фармакологические свойства гестагенов // Фарматека. – 2003. – № 8. – С. 33–41.Sergeev PV, Shimanovsky NL. Pharmacological properties of progestogens. Farmateka. 2003;(8):33–41. RussianCho B., Roh J.W., Park J. et al. Safety and Effectiveness of Dienogest (Visanne®) for Treatment of Endometriosis: A Large Prospective Cohort Study // Reprod Sci. – 2020. – Vol. 27, No. 4. – P. 905–915. DOI: 10.1007/s43032-019-00094-5Cho B, Roh JW, Park J, Jeong K, Kim TH, Kim YS, Kwon YS, Cho CH, Park SH, Kim SH. Safety and Effectiveness of Dienogest (Visanne®) for Treatment of Endometriosis: A Large Prospective Cohort Study. Reprod Sci. 2020;27(3):905–915. DOI: 10.1007/s43032-019-00094-5Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: a committee opinion // Fertil Steril. – 2014. – Vol. 101, No. 4. – P. 927–935. DOI: 10.1016/j.fertnstert.2014.02.012Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril. 2014;101(4):927–935. DOI: 10.1016/j.fertnstert.2014.02.012. Erratum in: Fertil Steril. 2015;104(2):498.Jeng C.J., Chuang L., Shen J. A comparison of progestogens or oral contraceptives and gonadotropin-releasing hormone agonists for the treatment of endometriosis: a systematic review // Expert Opin Pharmacother. – 2014. – Vol. 15, No. 6. – P. 767–773. DOI: 10.1517/14656566.2014.888414Jeng CJ, Chuang L, Shen J. A comparison of progestogens or oral contraceptives and gonadotropin-releasing hormone agonists for the treatment of endometriosis: a systematic review. Expert Opin Pharmacother. 2014;15(6):767–773. DOI: 10.1517/14656566.2014.888414Gokmen B.S., Selcuki N.F.T., Aydın A., Bahat P.Y., Akça A. Effects of Dienogest Therapy on Endometriosis-Related Dysmenorrhea, Dyspareunia, and Endometrioma Size // Cureus. – 2023. – Vol. 15, No. 1. – P. e34162. DOI: 10.7759/cureus.34162Saglik Gokmen B, Topbas Selcuki NF, Aydın A, Yalcin Bahat P, Akça A. Effects of Dienogest Therapy on Endometriosis-Related Dysmenorrhea, Dyspareunia, and Endometrioma Size. Cureus. 2023;15(1):e34162. DOI: 10.7759/cureus.34162Schindler A.E., Campagnoli C., Druckmann R., Huber J., Pasqualini J.R., Schweppe K.W., Thijssen J.H. Classification and pharmacology of progestins // Maturitas. – 2008. – Vol. 61, No. 1-2. – P. 171–180. DOI: 10.1016/j.maturitas.2008.11.013Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH. Classification and pharmacology of progestins. Maturitas. 2003;46 Suppl 1:S7–S16. DOI: 10.1016/j.maturitas.2003.09.014Chwalisz K., Surrey E., Stanczyk F.Z. The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis // Reprod Sci. – 2012. – Vol. 19, No. 6. – P. 563–571. DOI: 10.1177/1933719112438061Chwalisz K, Surrey E, Stanczyk FZ. The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis. Reprod Sci. 2012;19(6):563–571. DOI: 10.1177/1933719112438061Vercellini P., Bracco B., Mosconi P., Roberto A., Alberico D., Dhouha D., Somigliana E. Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study // Fertil Steril. – 2016. – Vol. 105, No. 3. – P. 734–743.e3. DOI: 10.1016/j.fertnstert.2015.11.016Vercellini P, Bracco B, Mosconi P, Roberto A, Alberico D, Dhouha D, Somigliana E. Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study. Fertil Steril. 2016;105(3):734–743.e3. DOI: 10.1016/j.fertnstert.2015.11.016Africander D., Verhoog N., Hapgood J.P. Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception // Steroids. – 2011. – Vol. 76, No. 7. – P. 636–652. DOI: 10.1016/j.steroids.2011.03.001Africander D, Verhoog N, Hapgood JP. Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception. Steroids. 2011;76(7):636–652. DOI: 10.1016/j.steroids.2011.03.001Flores V.A., Vanhie A., Dang T., Taylor H.S. Progesterone receptor status predicts clinical response to progestin treatment in women with endometriosis // Fertil Steril. – 2018. – Vol. 103, No. 12. – P. 4561–4568. DOI: 10.1210/jc.2018-01227Flores VA, Vanhie A, Dang T, Taylor HS. Progesterone Receptor Status Predicts Response to Progestin Therapy in Endometriosis. J Clin Endocrinol Metab. 2018;103(12):4561–4568. DOI: 10.1210/jc.2018-01227Vercellini P., Buggio L., Frattaruolo M.P., Borghi A., Dridi D., Somigliana E. Medical treatment of endometriosis-related pain // Best Practice & Research Clinical Obstetrics & Gynaecology. – 2018. – Vol. 51. – P. 68–91. DOI: 10.1016/j.bpobgyn.2018.01.015Vercellini P, Buggio L, Frattaruolo MP, Borghi A, Dridi D, Somigliana E. Medical treatment of endometriosis-related pain. Best Pract Res Clin Obstet Gynaecol. 2018;51:68–91. DOI: 10.1016/j.bpobgyn.2018.01.015Peng C., Huang Y., Zhou Y. Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis // Arch Gynecol Obstet. – 2021. – Vol. 304, No. 1. – P. 231–252. DOI: 10.1007/s00404-020-05900-zPeng C, Huang Y, Zhou Y. Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis. Arch Gynecol Obstet. 2021;304(1):231–252. DOI: 10.1007/s00404-020-05900-zБеженарь В.Ф., Круглов С.Ю., Кузьмина Н.С., Констанденкова А.С., Граматикова А.Г., Изоркина В.А., Григорян А.Э., Федосова Д.В., Исмогулова А.Б. Анализ эффективности различных методов ведения пациенток с эндометриозом и обоснование длительной персонализированной противорецидивной терапии дидрогестероном в рамках стратегии их комбинированного лечения // Проблемы репродукции. – 2024. – Т. 30, № 2. – С. 102–111. DOI: 10.17116/repro202430021102Bezhenar’ VF, Kruglov SYu, Kuzmina NS, Constandenkova AS, Gramatikova AG, Izorkina VA, Grigoryan AE, Fedosova DV, Ismogulova AB. Analysis of the effectiveness of various methods of managing patients with endometriosis and justification for long-term personalized anti-relapse therapy with dydrogesterone as part of their combination treatment strategy. Russian Journal of Human Reproduction. 2024;30(2):102–111. DOI: 10.17116/repro202430021102Trivedi P., Selvaraj K., Das Mahapatra P., Srivastava S., Malik S. Effective post-laparoscopic treatment of endometriosis with dydrogesterone // Gynecological Endocrinology. – 2007. – Vol. 23, No. S1. – P. 73–76. DOI: 10.1080/09513590701669583Trivedi P, Selvaraj K, Mahapatra PD, Srivastava S, Malik S. Effective post-laparoscopic treatment of endometriosis with dydrogesterone. Gynecol Endocrinol. 2007;23 Suppl 1:73–76. DOI: 10.1080/09513590701669583Сухих Г.Т., Адамян Л.В., Дубровина С.О., Баранов И.И., Беженарь В.Ф., Козаченко А.В., Радзинский В.Е., Оразов М.Р., Ярмолинская М.И., Олофссон Я.И. Пролонгированный циклический и непрерывный режимы применения дидрогестерона эффективны для уменьшения хронической тазовой боли у женщин с эндометриозом: результаты исследования «ОРХИДЕЯ» // Акушерство и гинекология. – 2021. – Т. 9, № 4. – С. 6–16. DOI: 10.1016/j.fertnstert.2021.07.1194Sukhikh G.N., Adamyan L.V., DubrovinaS.O., BaranovI.I., Bezhenar V.F., Kozachenko A.V., Radzinsky V.E., OrazovM.R., Yarmolinskaya M.I., Olofsson J.I. Prolonged cyclical and continuous regimens of dydrogesterone are effective for reducing chronic pelvic pain in women with endometriosis: results of the ORCHIDEA study. 2021;9(4):6–16. DOI: 10.1016/j.fertnstert.2021.07.1194Адамян Л.В., Мурватов К.Д., Киселев С.И., Арсланян К.Н., Чернецова А.С. Оценка эффективности диеногеста в терапии хронической тазовой боли у больных эндометриозом // Проблемы репродукции. – 2023. – Т. 29, № 2. – С. 51–56. DOI: 10.17116/repro20232902151 EDN: KRVDGVAdamyan LV, Murvatov KD, Kiselev SI, Arslanyan KN, Cheretsova AS. Evaluation of the effectiveness of dienogest in the treatment of chronic pelvic pain in patients with endometriosis. Russian Journal of Human Reproduction. 2023;29(2):51–56. DOI: 10.17116/repro20232902151 EDN: KRVDGVSamy A., Taher A., Sileem S.A., Abdelhakim A.M., Fathi M., Haggag H., Ashour K., Ahmed S.A., Shareef M.A., AlAmodi A.A., Keshta N.H.A., Shatat H.B.A.E., Salah D.M., Ali A.S., El Kattan E.A.M., Elsherbini M. Medical therapy options for endometriosis related pain, which is better? A systematic review and network meta-analysis of randomized controlled trials // J Gynecol Obstet Hum Reprod. – 2021. – Vol. 50, No. 1. – P. 101798. DOI: 10.1016/j.jogoh.2020.101798Samy A, Taher A, Sileem SA, Abdelhakim AM, Fathi M, Haggag H, Ashour K, Ahmed SA, Shareef MA, AlAmodi AA, Keshta NHA, Shatat HBAE, Salah DM, Ali AS, El Kattan EAM, Elsherbini M. Medical therapy options for endometriosis related pain, which is better? A systematic review and network meta-analysis of randomized controlled trials. J Gynecol Obstet Hum Reprod. 2021;50(1):101798. DOI: 10.1016/j.jogoh.2020.101798Caruso S., Cianci A., Iraci Sareri M., Panella M., Caruso G., Cianci S. Randomized study on the effectiveness of nomegestrol acetate plus 17β-estradiol oral contraceptive versus dienogest oral pill in women with suspected endometriosis associated chronic pelvic pain // BMC Women’s Health. – 2022. – Vol. 22, No. 1. – P. 146. DOI: 10.1186/s12905-022-01737-7Caruso S, Cianci A, Iraci Sareri M, Panella M, Caruso G, Cianci S. Randomized study on the effectiveness of nomegestrol acetate plus 17β-estradiol oral contraceptive versus dienogest oral pill in women with suspected endometriosis associated chronic pelvic pain. BMC Womens Health. 2022;22(1):146. DOI: 10.1186/s12905-022-01737-7Atlihan U., Yavuz O., Ata C., Avsar H.A., Erkilinc S. Effects of dienogest treatment on endometrioma-related clinical symptoms and endometrioma size: retrospective cohort study // Front Med (Lausanne). – 2025. – Vol. 12. – P. 1581661. DOI: 10.3389/fmed.2025.1581661Atlihan U, Yavuz O, Ata C, Avsar HA, Erkilinc S. Effects of dienogest treatment on endometrioma-related clinical symptoms and endometrioma size: retrospective cohort study. Front Med (Lausanne). 2025;12:1581661. DOI: 10.3389/fmed.2025.1581661Andres M.P., Lopes L.A., Baracat E.C., Podgaec S. Dienogest in the treatment of endometriosis: systematic review // Arch Gynecol Obstet. – 2015. – Vol. 292, No. 3. – P. 523–529. DOI: 10.1007/s00404-015-3681-6Andres Mde P, Lopes LA, Baracat EC, Podgaec S. Dienogest in the treatment of endometriosis: systematic review. Arch Gynecol Obstet. 2015;292(3):523–529. DOI: 10.1007/s00404-015-3681-6Muzii L., Di Tucci C., Galati G., Carbone F., Palaia I., Bogani G., Perniola G., Tomao F., Kontopantelis E., Di Donato V. The Efficacy of Dienogest in Reducing Disease and Pain Recurrence After Endometriosis Surgery: a Systematic Review and Meta-Analysis // Reprod Sci. – 2023. – Vol. 30, No. 11. – P. 3135–3143. DOI: 10.1007/s43032-023-01266-0Muzii L, Di Tucci C, Galati G, Carbone F, Palaia I, Bogani G, Perniola G, Tomao F, Kontopantelis E, Di Donato V. The Efficacy of Dienogest in Reducing Disease and Pain Recurrence After Endometriosis Surgery: a Systematic Review and Meta-Analysis. Reprod Sci. 2023;30(11):3135–3143. DOI: 10.1007/s43032-023-01266-0Gurbuz T.B., Aslan K., Kasapoglu I., Muzii L., Uncu G. Norethindrone acetate versus dienogest for pain relief in endometriosis related pain: A randomized controlled trial // Eur J Obstet Gynecol Reprod Biol. – 2025. – Vol. 310. – P. 113940. DOI: 10.1016/j.ejogrb.2025.113940Gurbuz TB, Aslan K, Kasapoglu I, Muzii L, Uncu G. Norethindrone acetate versus dienogest for pain relief in endometriosis related pain: A randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2025;310:113940. DOI: 10.1016/j.ejogrb.2025.113940Morotti M., Venturini P.L., Biscaldi E., Racca A., Calanni L., Vellone V.G., Stabilini C., Ferrero S. Efficacy and acceptability of long-term norethindrone acetate for the treatment of rectovaginal endometriosis // Eur J Obstet Gynecol Reprod Biol. – 2017. – Vol. 213. – P. 4–10.DOI: 10.1016/j.ejogrb.2017.03.033Morotti M, Venturini PL, Biscaldi E, Racca A, Calanni L, Vellone VG, Stabilini C, Ferrero S. Efficacy and acceptability of long-term norethindrone acetate for the treatment of rectovaginal endometriosis. Eur J Obstet Gynecol Reprod Biol. 2017;213:4–10. DOI: 10.1016/j.ejogrb.2017.03.033Ferrero S., Camerini G., Ragni N., Venturini P.L., Biscaldi E., Remorgida V. Norethisterone acetate in the treatment of colorectal endometriosis: a pilot study // Hum Reprod. – 2010. – Vol. 25, No. 1. – P. 94–100. DOI: 10.1093/humrep/dep361Ferrero S, Camerini G, Ragni N, Venturini PL, Biscaldi E, Remorgida V. Norethisterone acetate in the treatment of colorectal endometriosis: a pilot study. Hum Reprod. 2010;25(1):94–100. DOI: 10.1093/humrep/dep361Kaser D.J., Missmer S.A., Berry K.F., Laufer M.R. Use of norethindrone acetate alone for postoperative suppression of endometriosis symptoms // J Pediatr Adolesc Gynecol. – 2012. – Vol. 25, No. 2. – P. 105–108. DOI: 10.1016/j.jpag.2011.09.013Kaser DJ, Missmer SA, Berry KF, Laufer MR. Use of norethindrone acetate alone for postoperative suppression of endometriosis symptoms. J Pediatr Adolesc Gynecol. 2012;25(2):105–108. DOI: 10.1016/j.jpag.2011.09.013Strowitzki T., Faustmann T., Gerlinger C., Schumacher U., Ahlers C., Seitz C. Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program // Int J Womens Health. – 2015. – Vol. 7. – P. 393–401. DOI: 10.2147/IJWH.S77202Strowitzki T, Faustmann T, Gerlinger C, Schumacher U, Ahlers C, Seitz C. Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program. Int J Womens Health. 2015;7:393–401. DOI: 10.2147/IJWH.S77202La Torre F., Vannuccini S., Toscano F., Gallucci E., Orlandi G., Manzi V., Petraglia F. Long-term treatment for endometriosis with dienogest: efficacy, side effects and tolerability // Gynecol Endocrinol. – 2024. – Vol. 40, No. 1. – P. 2336121. DOI: 10.1080/09513590.2024.2336121La Torre F, Vannuccini S, Toscano F, Gallucci E, Orlandi G, Manzi V, Petraglia F. Long-term treatment for endometriosis with dienogest: efficacy, side effects and tolerability. Gynecol Endocrinol. 2024;40(1):2336121. DOI: 10.1080/09513590.2024.2336121Nezhat C., Vang N., Tanaka P.P. Optimal management of endometriosis and pain Obstet Gynecol. – 2019. – Vol. 134, No. 4. – P. 834–839. DOI: 10.1097/AOG.0000000000003461. Erratum in: Obstet Gynecol. – 2020. – Vo. 135, No. 5. – P. 1233. DOI: 10.1097/AOG.0000000000003852Nezhat C, Vang N, Tanaka PP, Nezhat C. Optimal Management of Endometriosis and Pain. Obstet Gynecol. 2019;134(4):834–839. DOI: 10.1097/AOG.0000000000003461. Erratum in: Obstet Gynecol. 2020;135(5):1233. DOI: 10.1097/AOG.0000000000003852Беженарь В.Ф., Молчанов О.Л., Пастушенков В.Л., Констанденкова А.С., Кузьмина Н.С., Круглов С.Ю., Граматикова А.Г. Роль сенсибилизации к прогестерону в оптимизации лечения эндометриоз-ассоциированной тазовой боли // Акушерство и гинекология. – 2023. – Т. 7. – С. 109–118. DOI: 10.18565/aig.2023.73 EDN: RKLIRHBezhenar VF, Molchanov OL, Pastushenkov VL, Konstandenkova AS, Kuzmina NS, Kruglov SYu, Gramatikova AG. The role of sensitization to progesterone in improving the treatment of endometriosis-associated pelvic pain. Obstetrics and Gynecology. 2023;7:109–118. DOI: 10.18565/aig.2023.73 EDN: RKLIRHBedaiwy M.A., Allaire C., Alfaraj S. Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy // Fertil Steril. – 2017. – Vol. 107, No. 3. – P. 537–548. DOI: 10.1016/j.fertnstert.2016.12.024Bedaiwy MA, Allaire C, Alfaraj S. Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy. Fertil Steril. 2017;107(3):537–548. DOI: 10.1016/j.fertnstert.2016.12.024Casper R.F. Progestin-only pills may be a better first-line treatment for endometriosis than combined estrogen-progestin contraceptive pills // Fertil Steril. – 2017. – Vol. 107. – P. 533–536. DOI: 10.1016/j.fertnstert.2017.01.003Casper RF. Progestin-only pills may be a better first-line treatment for endometriosis than combined estrogen-progestin contraceptive pills. Fertil Steril. 2017;107(3):533–536. DOI: 10.1016/j.fertnstert.2017.01.003McNamara H.C., Frawley H.C., Donoghue J.F., Readman E., Healey M., Ellett L., Reddington C., Hicks L.J., Harlow K., Rogers P.A.W., Cheng C. Peripheral, central, and cross sensitization in endometriosis-associated pain and comorbid pain syndromes // Frontiers in Reproductive Health. – 2021. – Vol. 3. – P. 729642. DOI: 10.3389/frph.2021.729642McNamara HC, Frawley HC, Donoghue JF, Readman E, Healey M, Ellett L, Reddington C, Hicks LJ, Harlow K, Rogers PAW, Cheng C. Peripheral, Central, and Cross Sensitization in Endometriosis-Associated Pain and Comorbid Pain Syndromes. Front Reprod Health. 2021;3:729642. DOI: 10.3389/frph.2021.729642

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