Experience with bovhyaluronidaze azoximer used in the complex treatment of endometriosis: results of the ISLAND INTRA study
Dubrovina S.O., Vovkochina M.A., Berlim Yu.D., Aleksandrina A.A., Bogunova D.Yu.
Background: Fibrosis is one of the key mechanisms responsible for developing endometriosis. Therefore, the effectiveness of treating various forms of endometriosis using antifibrotic therapy, such as Longidaza (bovhyaluronidaze azoximer), is of great importance for practice and requires further study.
Objective: To compare the results of the complex therapy with progestogen and Longidaza (3000 IU lyophilizate and 3000 IU suppositories) with progestogen monotherapy in patients with endometriosis and pain syndrome.
Materials and methods: The study included 72 patients aged 35 to 50 diagnosed with endometriosis. The patients were prescribed progestogen monotherapy (the comparison group included 35 women) or the combined therapy with progestogen and Longidaza (3000 IU lyophilizate injected intramuscularly once every 3 days, 10 injections for 30 days) followed by the administration of Longidaza suppositories 3000 IU rectally once every 5 days, a total of 20 suppositories (the main group included 37 women). The severity of pelvic pain was assessed using the VAS scale, and the quality of life was evaluated using the SF-20 questionnaire after 30 and 120 days. The data of the ultrasound examinations were analyzed to determine the frequency of the fan-shaped shadow of the small focal formations indicator.
Results: The treatment was completed by 66 patients, namely by 34 women from the main group and 32 women from the comparison group. On day 30, the incidence of complaints in the combination therapy group was lower that one in the monotherapy group: 18/34 (52.9%) versus 25/32 (78.1%), respectively (p=0.041). The analysis of pain syndrome using the VAS scale in each of the groups showed a significant decrease in pain levels compared to the initial level by the 30th day of therapy (р<0.001). In the combination therapy group, the pain level was more decreased than one in the monotherapy group: -2.5 [-6.0; -1.0] and -1.0 [-4.0; 0.0], respectively (p=0.039). According to the ultrasound results, the proportion of patients with the fan-shaped shadow of the small focal formations decreased from 15/34 (44.1%) to 9/34 (26.5%) (p=0.041) by the 120th day. The decrease was not significant in the monotherapy group, namely from 9/32 (28.1%) to 6/32 (18.8%) (p=0.317).
Conclusion: The results of the study demonstrate the benefits of using progestogen in combination with Longidaza in the treatment of patients with endometriosis.
Authors’ contributions: Dubrovina S.O. – developing the concept and design of the study, writing the article; Berlim Yu.D., Aleksandrina A.A., Vovkochina M.A., Bogunova D.Yu. – collecting and processing the material, writing the article.
Conflicts of interest: Authors declare lack of the possible conflicts of interests.
Funding: The study was conducted without sponsorship.
Patients’ Consent for Publication: The patients signed informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Dubrovina S.O., Vovkochina M.A., Berlim Yu.D., Aleksandrina A.A., Bogunova D.Yu.
Experience with bovhyaluronidaze azoximer used in the complex treatment of endometriosis: results of the ISLAND INTRA study.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (7): 145-152 (in Russian)
https://dx.doi.org/10.18565/aig.2025.64Authors’ contributions: Dubrovina S.O. – developing the concept and design of the study, writing the article; Berlim Yu.D., Aleksandrina A.A., Vovkochina M.A., Bogunova D.Yu. – collecting and processing the material, writing the article.
Conflicts of interest: Authors declare lack of the possible conflicts of interests.
Funding: The study was conducted without sponsorship.
Patients’ Consent for Publication: The patients signed informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Dubrovina S.O., Vovkochina M.A., Berlim Yu.D., Aleksandrina A.A., Bogunova D.Yu.
Experience with bovhyaluronidaze azoximer used in the complex treatment of endometriosis: results of the ISLAND INTRA study.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (7): 145-152 (in Russian)
https://dx.doi.org/10.18565/aig.2025.64
Keywords
bovhyaluronidaze azoximer
dienogest
pain syndrome
quality of life
endometriosis
References
- Всемирная организация здравоохранения. Информационный бюллетень. Эндометриоз. Доступно по: https://www.who.int/ru/news-room/fact-sheets/detail/endometriosis [World Health Organization. Fact sheet. Endometriosis. Available at: https://www.who.int/ru/news-room/fact-sheets/detail/endometriosis].
- van Aken M.A.W., Oosterman J.M., van Rijn C.M., Ferdek M.A., Ruigt G.S.F., Peeters B.W.M.M. et al. Pain cognition versus pain intensity in patients with endometriosis: toward personalized treatment. Fertil. Steril. 2017; 108(4): 679-86. https://dx.doi.org/10.1016/j.fertnstert.2017.06.024
- Романова О.А., Чуркин К.С., Печеникова В.А. Зона соединения эндо- и миометрия: морфофункциональные особенности и значение в развитии акушерско-гинекологической патологии. Вестник Российcкой военно-медицинской академии. 2017; 19(2): 201-5. [Romanova O.A., Churkin K.S., Pechenikova V.A. Junctional zone of endo- and myometrium: morphological and functional features and its role in obstetrical and gynecological pathology. Bulletin of the Russian Military Medical Academy. 2017; 19(2): 201-5 (in Russian)]. https://dx.doi.org/10.17816/brmma623378
- Vissers G., Giacomozzi M., Verdurmen W., Peek R., Nap A. The role of fibrosis in endometriosis: a systematic review. Hum. Reprod. Update. 2024; 30(6): 706-50. https://dx.doi.org/10.1093/humupd/dmae023
- Дубровина С.О., Берлим Ю.Д., Александрина А.Д., Богунова Д.Ю., Лесной М.Н. Эндометриоз и спаечный процесс: что мы знаем и что можем. Гинекология. 2020; 22(6): 32-7. [Dubrovina S.O., Berlim Yu.D., Alexandrina A.D., Bogunova D.U., Lesnoy M.N. Endometriosis and adhesion process: what we know and what we can. Gynecology. 2020; 22(6): 32-7 (in Russian)]. https://dx.doi.org/10.26442/20795696.2020.6.200569
- Тимофеева Ю.С., Маринкин И.О., Кулешов В.М., Айдагулова С.В. Патогенез боли при эндометриозе. Акушерство и гинекология. 2022; 9: 12-8. [Timofeeva Yu.S., Marinkin I.O., Kuleshov V.M., Aidagulova S.V. Pathogenesis of pain in endometriosis. Obstetrics and Gynecology. 2022; (9): 12-8 (in Russian)]. https://dx.doi.org/10.18565/aig.2022.9.12-18
- Сухих 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; 5: 159-76. [Sukhikh G.T., Serov V.N., Adamyan L.V., Baranov I.I., Bezhenar V.F., Gabidullina R.I., Dubrovina S.O., Kozachenko A.V., Podzolkova N.M., Smetnik A.A., Tapilskaya N.I., Uvarova E.V., Shikh E.V., Yarmolinskaya M.I. 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): 159-16 (in Russian)]. https://dx.doi.org/10.18565/aig.2023.132
- Оразов М.Р., Радзинский В.Е., Хамошина М.Б., Духин А.О., Токтар Л.Р., Орехов Р.Е., Читанава Ю.С. Эффективность комплексной терапии тазовой боли, ассоциированной с аденомиозом. Трудный пациент. 2020; 18(4): 34-40. [Orazov M.R., Radzinskiy V.E., Khamoshina M.B., Dukhin A.O., Toktar L.R., Chitavava Yu.S. Effectiveness of complex therapy of pelvic pain associated with adenomyosis. Difficult Patient. 2020; 18(4): 34-40 (in Russian)]. https://dx.doi.org/10.24411/2074-1995-2020-10028
- Ярмолинская М.И., Радзинский В.Е., Оразов М.Р., Коротких И.Н., Зиганшин О.Р., Еремина Н.А., Хобец В.В. Оценка эффективности бовгиалуронидазы азоксимера в комбинированном лечении больных наружным генитальным эндометриозом на основании результатов многоцентрового проспективного неинтервенционного исследования (ISLAND). Гинекология. 2021; 23(5): 392-401. [Yarmolinskaya M.I., Radzinsky V.E., Orazov M.R., Korotkikh I.N., Ziganshin O.R., Eremina N.A., Khobets V.V. Evaluation of bovhyaluronidase azoxymer efficacy in combined treatment of patients with endometriosis based on the results of multicenter prospective non-interventional study (ISLAND). Gynecology. 2021; 23(5): 392-401 (in Russian)]. https://doi.org/10.26442/20795696.2021.5.201211
- Дубровина С.О., Берлим Ю.Д. Медикаментозное лечение боли, связанной с эндометриозом. Акушерство и гинекология. 2019; 2: 34-40. [Dubrovina S.O., Berlim Yu.D. Drug treatment for endometriosis-related pain. Obstetrics and Gynecology. 2019; (2): 34-40. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.2.34-40
- Адамян Л.В., Пивазян Л.Г., Маилова К.С., Пешкова Ю.О., Степанян А.А. Экспериментальное моделирование, профилактика и лечение эндометриоз-ассоциированного спаечного процесса на клеточной линии NIH/3T3-фибробластов с применением бовгиалуронидазы азоксимер (in vitro). Проблемы репродукции. 2024; 30(6): 61-72. [Adamyan L.V., Pivazyan L.G., Mailova K.S., Peshkova Yu.O., Stepanian A.A. Experimental modeling, prevention, and treatment of endometriosis-associated adhesion formation in NIH/3T3 fibroblast cell line using bovhyaluronidase azoximer (in vitro). Russian Journal of Human Reproduction. 2024; 30(6): 61-72. (in Russian)]. https://dx.doi.org/10.17116/repro20243006161
- Almadani Y.H., Vorstenbosch J., Davison P.G., Murphy A.M. Wound healing: a comprehensive review. Semin. Plast. Surg. 2021; 35(3): 141-4. https://dx.doi.org/10.1055/s-0041-1731791
- Adler M., Mayo A., Zhou X., Franklin R.A., Meizlish M.L., Medzhitov R. et al. Principles of cell circuits for tissue repair and fibrosis. iScience. 2020; 23(2): 100841. https://dx.doi.org/10.1016/j.isci.2020.100841
- Hutchenreuther J., Leask A. A tale of two origins: do myofibroblasts originate from different sources in wound healing and fibrosis? Cell Tissue Res. 2016; 365(3): 507-9. https://dx.doi.org/10.1007/s00441-016-2419-5
- Bulun S.E., Yilmaz B.D., Sison C., Miyazaki K., Bernardi L., Liu S. et al. Endometriosis. Endocr. Rev. 2019; 40(4): 1048-79. https://dx.doi.org/10.1210/er.2018-00242
- Vercellini P., Buggio L., Berlanda N., Barbara G., Somigliana E., Bosari S. Estrogen-progestins and progestins for the management of endometriosis. Fertil. Steril. 2016; 106(7): 1552-71.e2. https://dx.doi.org/10.1016/j.fertnstert.2016.10.022
- Patel B.G., Rudnicki M., Yu.J., Shu Y., Taylor R.N. Progesterone resistance in endometriosis: origins, consequences and interventions. Acta Obstet. Gynecol. Scand. 2017; 96(6): 623-32. https://dx.doi.org/10.1111/aogs.13156
- Kempers R.D., Dockerty M.B., Hunt A.B., Symmonds R.E. Significant postmenopausal endometriosis. Surg. Gynecol. Obstet. 1960; 111: 348-56.
- Boneva R.S., Lin J.S., Wieser F., Nater U.M., Ditzen B., Taylor R.N. et al. Endometriosis as a comorbid condition in chronic fatigue syndrome (CFS): secondary analysis of data from a CFS Case-Control Study. Front. Pediatr. 2019; 7: 195. https://dx.doi.org/10.3389/fped.2019.00195.
- Sam M., Raubenheimer M., Manolea F., Aguilar H., Mathew R.P., Patel V.H. et al. Accuracy of findings in the diagnosis of uterine adenomyosis on ultrasound. Abdom. Radiol. (NY). 2020; 45(3): 842-50. https://dx.doi.org/10.1007/s00261-019-02231-9.
- Cunningham R.K., Horrow M.M., Smith R.J., Springer J. Adenomyosis: a sonographic diagnosis. Radiographics. 2018; 38(5): 1576-89. https://dx.doi.org/10.1148/rg.2018180080
- Andres M.P., Borrelli G.M., Ribeiro J., Baracat E.C., Abrão M.S., Kho R.M. Transvaginal ultrasound for the diagnosis of adenomyosis: systematic review and meta-analysis. J. Minim. Invasive Gynecol. 2018; 25(2): 257-64. https://dx.doi.org/10.1016/j.jmig.2017.08.653
- Mechsner S., Schwarz J., Thode J., Loddenkemper C., Salomon D.S., Ebert A.D. Growth-associated protein 43-positive sensory nerve fibers accompanied by immature vessels are located in or near peritoneal endometriotic lesions. Fertil. Steril. 2007; 88(3): 581-7. https://dx.doi.org/10.1016/j.fertnstert.2006.12.087
Received 06.03.2025
Accepted 11.07.2025
About the Authors
Svetlana O. Dubrovina, Professor, Dr. Med. Sci., Chief Researcher, Obstetrics and Pediatrics Research Institute, RostSMU, Ministry of Health of Russia; Professor at the Department of Obstetrics and Gynecology No. 1, RostSMU, Ministry of Health of Russia, 344012, Russia, Rostov-on-Don, Mechnikov str., 43, +7(863)250-42-00, s.dubrovina@gmail.comMarina A. Vovkochina, obstetrician-gynecologist, Obstetrics and Pediatrics Research Institute, Rostov SMU, Ministry of Health of Russia,
344012, Russia, Rostov-on-Don, Mechnikov str., 43, +7(918)559-00-30, jordan-85@inbox.ru
Yulia D. Berlim, PhD, Teaching Assistant at the Department of Obstetrics and Gynecology, Bashkir SMU, Ministry of Health of Russia,
450008, Russia, Republic of Bashkortostan, Ufa, Lenin str., 3, +7(918)500-23-56, juliaberlim@yandex.ru
Anna D. Alexandrina, obstetrician-gynecologist, City Emergency Hospital, 344068, Russia, Rostov-on-Don, Bodraya str., 88, +7(904)448-58-42, anna221215@inbox.ru
Diana Yu. Bogunova, doctor-PhD student of the 1st year of study, Department of Obstetrics and Gynecology No.1, Rostov SMU, Ministry of Health of Russia,
344022, Russia, Rostov-on-Don, Nakhichevansky lane, 29, +7(961)524-77-23, bogunovadi@yandex.ru
Similar Articles
