Ulyanovsk Medico-biological Journal

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DOI 10.34014/2227-1848-2026-1-18-30

PREDICTORS OF DRUG RESISTANCE DEVELOPMENT IN HORMONE THERAPY FOR ENDOMETRIOSIS

L.I. Trubnikova, I.I. Antoneeva, M.A. Iglina, A.V. Klykova, E.A. Dimitrienko

Ulyanovsk State University, Ulyanovsk, Russia

 

Endometriosis is a common gynecological condition that significantly impacts quality of life and reproductive function in women. Endometriosis is characterized by localized estrogen hypersensitivity and progesterone resistance. Hormonal therapy remains the primary medical treatment for this condition. Its pathogenetic basis is the temporary suppression of ovarian function to induce hypoestrogenism, which leads to the regression of endometriotic lesions. However, a significant proportion of patients experience an inadequate response to hormonal treatment or develop resistance to it.

The aim of the study is to analyze potential predictors of resistance to hormonal treatment in patients with endometriosis.

Materials and Methods. The authors reviewed the articles published in peer-reviewed journals indexed in PubMed, GoogleScholar, CyberLeninka, and the Russian Science Citation Index (RSCI) databases. The search was carried out using such keywords as ‘endometriosis,’ ‘hormonal therapy,’ ‘drug resistance,’ and ‘resistance predictors’. The search period covered from 2015 to 2023.

Results. The following potential predictors of resistance were identified: genetic polymorphisms in drug-metabolizing enzymes (CYP, NAT2) and sex hormone receptors (PROGINS), abnormalities in progesterone receptor expression in the endometrium, microRNAs dysregulation (miR-29c, miR-196a, miR-194-3p, miR-92a), a deeply infiltrative disease phenotype, and thickening of the endometrium during hormonal therapy.

Conclusion. Understanding and considering the multifactorial nature of drug resistance predictors offer promising avenues for optimizing and personalizing therapeutic strategies for endometriosis management.

Key words: endometriosis, hormonal therapy, drug resistance, resistance predictors.

 

Conflict of interest. The authors declare no conflict of interest.

Author contributions

Research concept and design: Iglina M.A., Trubnikova L.I., Antoneeva I.I.

Literature search: Iglina M.A., Klykova A.V., Dimitrienko E.A.

Statistical data processing: Klykova A.V., Dimitrienko E.A.

Data analysis and interpretation: Iglina M.A., Klykova A.V., Dimitrienko E.A.

Text writing and editing: Iglina M.A., Trubnikova L.I., Antoneeva I.I.

 

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Received May 05, 2025; accepted September 14, 2025.

 

Information about the authors

Trubnikova Larisa Ignat'evna, Doctor of Sciences (Medicine), Professor, Head of the Chair of Obstetrics and Gynecology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-0720-0369

Antoneeva Inna Ivanovna, Doctor of Sciences (Medicine), Professor, Chair of Oncology and Radiation Diagnostics named after O.P. Modnikov, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-1525-2070

Iglina Marina Aleksandrovna, Candidate of Sciences (Medicine), Associate Professor, Chair of Obstetrics and Gynecology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0008-5938-6370

Klykova Alina Vyacheslavovna, Postgraduate Student, Chair of Obstetrics and Gynecology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0005-8292-7460

Dimitrienko Ekaterina Aleksandrovna, Postgraduate Student, Chair of Obstetrics and Gynecology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0006-4786-8597

 

For citation

Trubnikova L.I., Antoneeva I.I., Iglina M.A., Klykova A.V., Dimitrienko E.A. Prediktory razvitiya lekarstvennoy rezistentnosti pri gormonal'noy terapii endometrioza [Predictors of drug resistance development in hormone therapy for endometriosis]. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2026; 1: 18–30. DOI: 10.34014/2227-1848-2026-1-18-30 (in Russian).

 

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УДК 618.11

DOI 10.34014/2227-1848-2026-1-18-30

ПРЕДИКТОРЫ РАЗВИТИЯ ЛЕКАРСТВЕННОЙ РЕЗИСТЕНТНОСТИ ПРИ ГОРМОНАЛЬНОЙ ТЕРАПИИ ЭНДОМЕТРИОЗА

Л.И. Трубникова, И.И. Антонеева, М.А. Иглина, А.В. Клыкова, Е.А. Димитриенко

ФГБОУ ВО «Ульяновский государственный университет», г. Ульяновск, Россия

Эндометриоз является распространенным гинекологическим заболеванием, оказывающим значительное негативное влияние на качество жизни и репродуктивную функцию женщин. Эндометриоз характеризуется локальным повышением чувствительности к эстрогенам и резистентностью к прогестерону. Основным методом медикаментозного лечения данного заболевания остается гормональная терапия, патогенетической основой которой является временное угнетение функции яичников с инициацией гипоэстрогении, приводящей к регрессу очагов эндометриоза. Однако у значительной части пациенток наблюдается недостаточный ответ на гормональные препараты или развитие резистентности к ним.

Цель - анализ потенциальных предикторов развития резистентности к гормональному лечению эндометриоза.

Материалы и методы. Осуществлен обзор статей, опубликованных в рецензируемых журналах, индексированных в базах данных PubMed, GoogleScholar, CyberLeninka и РИНЦ. Для поиска были использованы ключевые слова «эндометриоз», «гормональная терапия», «лекарственная резистентность», «предикторы резистентности». Горизонт поиска охватывал период 2015–2023 гг.

Результаты. Выявлены следующие потенциальные предикторы резистентности: генетические полиморфизмы в ферментах метаболизма лекарственных препаратов (CYP, NAT2) и рецепторах половых гормонов (PROGINS), аномалии экспрессии рецепторов прогестерона в эндометрии, нарушения регуляции микроРНК (miR-29c, miR-196a, miR-194-3p, miR-92a), глубокий инфильтративный фенотип заболевания и увеличение толщины эндометрия на фоне гормональной терапии.

Выводы. Понимание и учет многофакторного характера предикторов лекарственной устойчивости открывают перспективы для оптимизации и персонализации терапевтических стратегий лечения эндометриоза.

Ключевые слова: эндометриоз, гормональная терапия, лекарственная резистентность, предикторы резистентности.

 

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов

Концепция и дизайн исследования: Иглина М.А., Трубникова Л.И., Антонеева И.И.

Литературный поиск: Иглина М.А., Клыкова А.В., Димитриенко Е.А.

Статистическая обработка данных: Клыкова А.В., Димитриенко Е.А.

Анализ и интерпретация данных: Иглина М.А., Клыкова А.В., Димитриенко Е.А.

Написание и редактирование текста: Иглина М.А., Трубникова Л.И., Антонеева И.И.

 

Литература

  1. Shafrir A.L., Farland L.V., Shah D.K., Harris H.R., Kvaskoff M., Zondervan K., Missmer S.A. Risk for and consequences of endometriosis: a critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018; 51: 1–15.

  2. Reid R., Steel A., Wardle J., McIntyre E., Harnett J., Foley H., Adams J. The prevalence of self-reported diagnosed endometriosis in the Australian population: results from a nationally-representative survey. BMC Res Notes. 2019; 12: 1–6.

  3. Hickey M., Ballard K., Farquhar C. Endometriosis. BMJ. 2014; 348: g1752.

  4. Darbà J., Marsà A. Economic implications of endometriosis: A review. PharmacoEconomics. 2022; 40 (12): 1143–1158.

  5. Johnson N.P., Hummelshoj L., Adamson G.D. World endometriosis society consensus on the classification of endometriosis. Hum Reprod. 2017; 32: 315–324.

  6. Ramin-Wright A., Kohl Schwartz A.S., Geraedts K., Rauchfuss M., Wölfler M. M., Haeberlin F., von Orelli S., Eberhard M., Imthurn B., Imesch P., Fink D., Leeners B. Fatigue – a symptom in endometriosis. Hum Reprod. 2018; 33 (8): 1459–1465.

  7. Zondervan K.T., Becker C.M., Koga K., Missmer S.A., Taylor R.N., Vigano P. Endometriosis. Nat Rev Dis Primers. 2018; 4 (1): 9.

  8. Prescott J., Farland L.V., Tobias D.K., Gaskins A. J., Spiegelman D., Chavarro J.E., Rich-Edwards J.W., Barbieri R.L., Missmer S.A. A prospective cohort study of endometriosis and subsequent risk of infertility. Hum Reprod. 2016; 31 (7): 1475–1482.

  9. Taylor H.S., Kotlyar A.M., Flores V.A. Endometriosis is a chronic systemic disease: Clinical challenges and novel innovations. Lancet. 2021; 397: 839–852.

  10. Horne A.W., Missmer S.A. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022; 379: e070750.

  11. Donnez J., Dolmans M.M. Endometriosis and medical therapy: from progestogens to progesterone resistance to GnRH antagonists: a review. J Clin Med. 2021; 10 (5): 1085.

  12. Smolarz B., Szyłło K., Romanowicz H. Endometriosis: epidemiology, classification, pathogenesis, treatment and genetics (review of literature). Int J Mol Sci. 2021; 22 (19): 10554.

  13. Hughes C.L., Foster W.G., Agarwal S.K., Mettler L. The impact of endometriosis on the health of women. Biomed Res Int. 2015; 2015: 436593.

  14. Vercellini P., Buggio L., Berlanda N. Estrogen-progestins and progestins for the management of endometriosis. Fertil Steril. 2016; 106 (7): 1552–1571.e2.

  15. Barra F., Scala C., Ferrero S. Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis. Expert Opin Drug Metab Toxicol. 2018; 14 (4): 399–415.

  16. Brown J., Crawford T.J., Datta S., Prentice A. Oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev. 2018; 5 (5): CD001019.

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Поступила в редакцию 05.05.2025; принята 14.09.2025.

 

Авторский коллектив

Трубникова Лариса Игнатьевна – доктор медицинских наук, профессор, заведующий кафедрой акушерства и гинекологии, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-0720-0369

Антонеева Инна Ивановна – доктор медицинских наук, профессор кафедры онкологии и лучевой диагностики им. О.П. Модникова, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-1525-2070

Иглина Марина Александровна – кандидат медицинских наук, доцент кафедры акушерства и гинекологии, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0008-5938-6370

Клыкова Алина Вячеславовна – аспирант кафедры акушерства и гинекологии, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0005-8292-7460

Димитриенко Екатерина Александровна – аспирант кафедры акушерства и гинекологии, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0006-4786-8597

 

Образец цитирования

Трубникова Л.И., Антонеева И.И., Иглина М.А., Клыкова А.В., Димитриенко Е.А. Предикторы развития лекарственной резистентности при гормональной терапии эндометриоза. Ульяновский медико-биологический журнал. 2026; 1: 18–30. DOI: 10.34014/2227-1848-2026-1-18-30.