farmaecFARMAKOEKONOMIKA. Modern Pharmacoeconomics and PharmacoepidemiologyФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология2070-49092070-4933IRBIS LLC10.17749/2070-4909/farmakoekonomika.2025.350farmaec-1283Research ArticleORIGINAL ARTICLESОРИГИНАЛЬНЫЕ ПУБЛИКАЦИИNeutrophil extracellular trap biomarkers as indicators of vulvovaginal atrophy severity after cancer treatmentМаркеры нейтрофильных внеклеточных ловушек как индикаторы тяжести вульвовагинальной атрофии после противоопухолевой терапииhttps://orcid.org/0000-0002-7456-2386СолоповаА. Г.SolopovaA. G.

Солопова Антонина Григорьевна, д.м.н., проф. 

WoS ResearcherID: Q-1385-2015.

Scopus Author ID: 6505479504. 

ул. Большая Пироговская, д. 2, стр. 4, Москва 119991

Antonina G. Solopova, Dr. Sci. Med., Prof.

WoS ResearcherID: Q-1385-2015.

Scopus Author ID: 6505479504. 

8/2 Trubetskaya Str., Moscow 119048

https://orcid.org/0000-0002-0725-9686ХизроеваД. Х.KhizroevaJ. Kh.

Хизроева Джамиля Хизриевна, д.м.н., проф. 

WoS ResearcherID: F-8384-2017.

Scopus Author ID: 57194547147. 

ул. Большая Пироговская, д. 2, стр. 4, Москва 119991

Jamilya Kh. Khizroeva, Dr. Sci. Med., Prof.

WoS ResearcherID: F-8384-2017.

Scopus Author ID: 57194547147. 

8/2 Trubetskaya Str., Moscow 119048

jamatotu@gmail.comhttps://orcid.org/0000-0001-7930-6018ГридасоваО. С.GridasovaO. S.

Гридасова Ольга Сергеевна 

ул. Большая Пироговская, д. 2, стр. 4, Москва 119991; ул. 3-я Рощинская, д. 6, Москва 115191

Olga S. Gridasova

8/2 Trubetskaya Str., Moscow 119048;

6 3rd Rozhinskaya Str., Moscow 115191

olga_s@bk.ruhttps://orcid.org/0000-0001-8404-1042БицадзеВ. О.BitsadzeV. O.

Бицадзе Виктория Омаровна, д.м.н., проф., проф. РАН 

WoS ResearcherID: F-8409-2017.

Scopus Author ID: 6506003478.

ул. Большая Пироговская, д. 2, стр. 4, Москва 119991

Victoria O. Bitsadze, Dr. Sci. Med., Prof., Prof. of RAS

WoS ResearcherID: F-8409-2017.

Scopus Author ID: 6506003478. 

8/2 Trubetskaya Str., Moscow 119048

https://orcid.org/0000-0003-1115-3144ИвановА. Е.IvanovA. E.

Иванов Александр Евгеньевич, к.м.н. 

Загородное ш., д. 18А, стр. 7, Москва 117152

Aleksandr E. Ivanov, PhD 

18A bldg 7, Zagorodnoe Shosse, Moscow 117152

https://orcid.org/0000-0002-6619-6179ГалкинВ. Н.GalkinV. N.

Галкин Всеволод Николаевич, д.м.н., проф. 

Загородное ш., д. 18А, стр. 7, Москва 117152

18A bldg 7, Zagorodnoe Shosse, Moscow 117152

https://orcid.org/0000-0001-7415-4633МакацарияА. Д.MakatsariyaA. D.

Макацария Александр Давидович, д.м.н., проф., академик РАН 

WoS ResearcherID: M-5660-2016.

Scopus Author ID: 57222220144. 

ул. Большая Пироговская, д. 2, стр. 4, Москва 119991

Alexander D. Makatsariya, Dr. Sci. Med., Prof., Academician of RAS

WoS ResearcherID: M-5660-2016.

Scopus Author ID: 57222220144. 

8/2 Trubetskaya Str., Moscow 119048

Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет им. И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияSechenov UniversityRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет им. И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет); Клиника «Реал Транс Хайр Т»РоссияSechenov University; Clinic “Real Trans Hair T”Russian FederationГосударственное бюджетное учреждение здравоохранения г. Москвы «Городская клиническая больница им. С.С. Юдина Департамента здравоохранения г. Москвы»РоссияYudin City Clinical HospitalRussian Federation202522012026184550559Copyright © Solopova A.G., Khizroeva J.K., Gridasova O.S., Bitsadze V.O., Ivanov A.E., Galkin V.N., Makatsariya A.D., 20262026Солопова А.Г., Хизроева Д.Х., Гридасова О.С., Бицадзе В.О., Иванов А.Е., Галкин В.Н., Макацария А.Д.Solopova A.G., Khizroeva J.K., Gridasova O.S., Bitsadze V.O., Ivanov A.E., Galkin V.N., Makatsariya A.D.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacoeconomics.ru/jour/article/view/1283Background

Background. Vulvovaginal atrophy (VVA) following antitumor treatment is a common and clinically significant complication. At the same time, the immunoinflammatory mechanisms determining the severity and persistence of atrophic changes are yet to be sufficiently studied. The role of extracellular neutrophil traps (NETs) in the pathogenesis of genital tract mucosal damage remains virtually unexplored.

Objective

Objective: To evaluate blood levels of NET markers – citrullinated histone H3 (CitH3), myeloperoxidase (MPO), cathepsin G (CatG) – in various VVA phenotypes after antitumor therapy and to determine their significance as potential biomarkers of atrophy severity.

Material and methods

Material and methods. A cross-sectional comparative study enrolled 215 postmenopausal women divided into five groups as follows: VVA after surgical treatment (n=52), chemoradiotherapy (n=27), antiestrogenic therapy (n=48), VVA without a history of cancer (n=53), and control (n=35). Clinical symptoms, vaginal pH, vaginal health index (VHI), epithelial thickness, and plasma levels of CitH3, MPO, and CatG were evaluated. Statistical analysis was performed using the Mann–Whitney test with Bonferroni correction and calculation of the r effect size.

Results

Results. The NETs profile varied depending on the nature of the treatment received. Maximum levels of CitH3 (0,65 [0,50–0,80] ng/ml), MPO (24 [18–30] ng/ml) и CatG (14 [12–16] ng/ml) were found in women after chemoradiotherapy. Antiestrogenic therapy was accompanied by pronounced immunoinflammatory activation of NETs, while surgical menopause and VVA without a history of gynecological cancer were associated with moderate and minimal levels, respectively. Intergroup differences between the oncological groups and the control group were statistically significant (p<0.005) with a large effect size according to the Mann–Whitney criterion (r≥0.50).

Conclusion

Conclusion. VVA after antitumor therapy is characterized by various immunoinflammatory phenotypes, which are reflected in specific NET profiles. CitH3, MPO, and CatG can be considered pathogenetically significant markers reflecting the degree of immunoinflammatory changes in VVA, thus representing candidates for further research aimed at patient stratification and the development of personalized therapy.

Актуальность

Актуальность. Вульвовагинальная атрофия (ВВА) после противоопухолевого лечения является частым и клинически значимым осложнением, однако иммуновоспалительные механизмы, определяющие тяжесть и персистенцию атрофических изменений, изучены недостаточно. Роль внеклеточных ловушек нейтрофилов (англ. neutrophil extracellular traps, NETs) в патогенезе повреждения слизистой генитального тракта остается практически не исследованной.

Цель

Цель: оценить уровни NETs-маркеров цитруллинированного гистона Н3 (англ. citrullinated histone H3, CitH3), миелопероксидазы (англ. myeloperoxidase, MPO), катепсина G (англ. cathepsin G, CatG) в крови при различных фенотипах ВВА после противоопухолевой терапии и определить их значение как потенциальных биомаркеров тяжести атрофии.

Материал и методы

Материал и методы. Проведено поперечное сравнительное исследование 215 постменопаузальных женщин, распределенных на пять групп: ВВА после хирургического лечения (n=52), химиолучевой терапии (n=27), антиэстрогенной терапии (n=48), ВВА без онкологического анамнеза (n=53), контроль (n=35). Оценивали клинические симптомы, вагинальный рН, индекс вагинального здоровья (англ. vagina health index, VHI), толщину эпителия и уровни CitH3, MPO, CatG в плазме крови. Статистический анализ выполняли с использованием критерия Манна–Уитни с поправкой Бонферрони и расчетом размера эффекта r.

Результаты

Результаты. NETs-профиль был разным в зависимости от характера перенесенного лечения. Максимальные уровни CitH3 (0,65 [0,50–0,80] нг/мл), MPO (24 [18–30] нг/мл) и CatG (14 [12–16] нг/мл) выявлены у женщин после химиолучевой терапии. Антиэстрогенная терапия сопровождалась выраженной иммуновоспалительной активацией NETs, хирургическая менопауза – умеренной, ВВА без онкогинекологического анамнеза – минимальной. Межгрупповые различия между онкологическими группами и контрольной группой были статистически значимы (p<0,005) с крупным размером эффекта по критерию Манна–Уитни (r≥0,50).

Заключение

Заключение. ВВА после противоопухолевой терапии характеризуется различными иммуновоспалительными фенотипами, которые отражаются в специфических NETs-профилях. CitH3, MPO и CatG могут рассматриваться как патогенетически значимые маркеры, отражающие степень иммуновоспалительных изменений при ВВА, и быть кандидатами для дальнейших исследований, направленных на стратификацию пациенток и разработку персонифицированной терапии.

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