Preview

Obstetrics, Gynecology and Reproduction

Advanced search

The role of C3 and C4 complement components in postmenopausal vulvovaginal atrophy with a different clinical history

https://doi.org/10.17749/2313-7347/ob.gyn.rep.2025.708

Abstract

Introduction. Vulvovaginal atrophy (VVA) is characterized by severe hypoestrogenism, impaired microcirculation, chronic inflammation, and decreased mucosal regeneration. In women with a varying clinical history, including applied antitumor treatment, such changes may differ in severity level. Despite that the role for pro-inflammatory cytokines in VVA has been extensively investigated, systemic immuno-inflammatory changes, primarily resulting in complement activation remained understudied.

Aim: to assess blood serum levels of C3 and C4 complement component levels in postmenopausal women with VVA coupled to clinical history, including various types of antitumor therapy, as well as in women without oncology history and in control group of healthy women.

Materials and Methods. A cross-sectional comparative study included five groups of postmenopausal women (n = 215): VVA after radical surgery (n = 52); VVA after chemoradiotherapy (CRT) (n = 27); VVA during antiestrogen therapy (n = 48); VVA without oncology history (n = 53); control group – healthy postmenopausal women (n = 35). The blood serum C3 and C4 levels were quantitated by immunoturbidimetry. The statistical analysis included the Kruskal–Wallis criterion and pairwise intergroup comparisons using the Mann–Whitney criterion with the Bonferroni correction.

Results. In all studied groups C3 and C4 levels were within the reference range, however, they differed significantly between the groups depending on the clinical history. The most prominent intergroup differences were observed in patients after CRT, who had higher C3 (1.62 g/L) and C4 (0.32 g/L) levels compared with control group (1.12 g/L for C3; 0.19 g/L for C4). In antiestrogenic therapy group (group 3) and surgical treatment group (group 1), C3 (1.48 g/L and 1.35 g/L, respectively) and C4 (0.28 g/L and 0.25 g/L, respectively) levels held an intermediate place between CRT group and control group. In women with VVA without oncology history, C3 (1.28 g/L) and C4 (0.23 g/L) levels were comparable to those in control group.

Conclusion. The data obtained evidence about variability of the systemic immuno-inflammatory profile in VVA driven by patient clinical history. Within the framework of the study, changes in C3 and C4 levels reflected general intergroup differences, which, however, remained within the reference range. The results emphasize a need for further research aimed at studying activated complement system components and their clinical significance in VVA.

About the Authors

O. S. Gridasova
Clinic "Real Trans Hair"
Russian Federation

Olga S. Gridasova, MD

6 3-ya Rozhinskaya Str., Moscow 115191



A. G. Solopova
Sechenov University
Russian Federation

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

 



J. Kh. Khizroeva
Sechenov University
Russian Federation

Jamilya Kh. Khizroeva, Dr Sci Med, Prof. 

Scopus Author ID: 57194547147. WoS ResearcherID: F-8384-2017

8 bldg. 2, Trubetskaya Str., Moscow 119048



V. O. Bitsadze
Sechenov University
Russian Federation

Victoria O. Bitsadze, MD, Dr Sci Med, Prof., Professor RAS

Scopus Author ID: 6506003478. WoS ResearcherID: F-8409-2017

8 bldg. 2, Trubetskaya Str., Moscow 119048



A. E. Ivanov
Yudin City Clinical Hospital, Moscow Healthcare Department
Russian Federation

Alexander E. Ivanov, MD, PhD.

18A bldg. 7, Zagorodnoe Shosse, Moscow 117152



V. N. Galkin
Yudin City Clinical Hospital, Moscow Healthcare Department
Russian Federation

Vsevolod N. Galkin, MD, Dr Sci Med, Prof. 

18A bldg. 7, Zagorodnoe Shosse, Moscow 117152



A. D. Makatsariya
Sechenov University
Russian Federation

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

Scopus Author ID: 57222220144. WoS ResearcherID: M-5660-2016

8 bldg. 2, Trubetskaya Str., Moscow 119048



References

1. Cox P., Panay N. Vulvovaginal atrophy in women after cancer. Climacteric. 2019;22(6):565–71. https://doi.org/10.1080/13697137.2019.1643180.

2. Ampilogova D.М., Solopova А.G., Blinov D.V. et al. The effectiveness of rehabilitation in vulvovaginal atrophy. [Effektivnost' reabilitacii pri vul'vovaginal'noj atrofii]. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2024;17(2):200–11. (In Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2024.258.

3. Vorobev A.V., Hajiyeva A.B., Son E.A. Effect of a rehabilitation program on magnesium levels in women with vulvovaginal atrophy in surgical menopause. [Vliyanie reabilitacionnoj programmy na uroven' magniya u zhenshchin s vul'vovaginal'noj atrofiej v hirurgicheskoj menopauze]. Journal of Medical Rehabilitation. 2024;2(4):336–43. (In Russ.). https:// doi.org/10.17749/2949-5873/rehabil.2024.25.

4. Gridasova O.S., Solopova A.G., Rumyantseva E.I. et al. Current approaches to the treatment of vulvovaginal atrophy in women with gynecological and breast cancer. [Sovremennye podhody k lecheniyu vul'vovaginal'noj atrofii u zhenshchin s ginekologicheskim rakom i rakom molochnyh zhelez]. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2025;18(2):284–293. (In Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2025.314.

5. Shifren J.L., Gass M.L.; NAMS Recommendations for Clinical Care of Midlife Women Working Group. The North American Menopause Society recommendations for clinical care of midlife women. Menopause. 2014;21(10):1038–62. https://doi.org/10.1097/GME.0000000000000319.

6. Pérez-López F.R., Phillips N., Vieira-Baptista P. et al. Management of postmenopausal vulvovaginal atrophy: recommendations of the International Society for the Study of Vulvovaginal Disease. Gynecol Endocrinol. 2021;37(8):746–52. https://doi.org/10.1080/09513590.2021.1943346.

7. Cucinella L., Tiranini L., Cassani C. et al. Genitourinary syndrome of menopause in breast cancer survivors: current perspectives on the role of laser therapy. Int J Womens Health. 2023;15:1261–82. https://doi.org/10.2147/IJWH.S414509.

8. Walport M.J. Complement. First of two parts. N Engl J Med. 2001;344(14):1058–66. https://doi.org/10.1056/NEJM200104053441406.

9. Blom A.M. The role of complement inhibitors beyond controlling inflammation. J Intern Med. 2017;282(2):116–28. https://doi.org/10.1111/joim.12606.

10. Mastellos D.C., Hajishengallis G., Lambris J.D. A guide to complement biology, pathology and therapeutic opportunity. Nat Rev Immunol. 2024;24(2):118–41. https://doi.org/10.1038/s41577-023-00926-1.

11. de Boer E.C.W., van Mourik A.G., Jongerius I. Therapeutic lessons to be learned from the role of complement regulators as double-edged sword in health and disease. Front Immunol. 2020;11:578069. https://doi.org/10.3389/fimmu.2020.578069.

12. Speidl W.S., Kastl S.P., Huber K., Wojta J. Complement in atherosclerosis: friend or foe? J Thromb Haemost. 2011;9(3):428–40. https://doi.org/10.1111/j.1538-7836.2010.04172.x.

13. Muscari A., Bozzoli C., Puddu G.M. et al. Association of serum C3 levels with the risk of myocardial infarction. Am J Med. 1995;98(4):357–64. https://doi.org/10.1016/S0002-9343(99)80314-3.

14. El Khoudary S.R., Chen X., McConnell D. et al. Associations of HDL subclasses and lipid content with complement proteins over the menopause transition: The SWAN HDL ancillary study: HDL and complement proteins in women. J Clin Lipidol. 2022;16(5):649–57. https://doi.org/10.1016/j.jacl.2022.07.015.

15. El Khoudary S.R., Shields K.J., Chen H.Y., Matthews K.A. Menopause, complement, and hemostatic markers in women at midlife: the Study of Women's Health Across the Nation. Atherosclerosis. 2013;231(1):54– 8. https://doi.org/10.1016/j.atherosclerosis.2013.08.039.

16. Narutytė R., Žukienė G., Bartkevičienė D. Vulvovaginal atrophy following treatment for oncogynecologic pathologies: etiology, epidemiology, diagnosis, and treatment options. Medicina (Kaunas). 2024;60(10):1584. https://doi.org/10.3390/medicina60101584.

17. Surace L., Lysenko V., Fontana A.O. et al. Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response. Immunity. 2015;42(4):767–77. https://doi.org/10.1016/j.immuni.2015.03.009.

18. Camon C., Garratt M., Correa S.M. Exploring the effects of estrogen deficiency and aging on organismal homeostasis during menopause. Nat Aging. 2024;4(12):1731–44. https://doi.org/10.1038/s43587-02400767-0.

19. Michaud M., Balardy L., Moulis G. et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14(12):877– 82. https://doi.org/10.1016/j.jamda.2013.05.009.

20. Khan Q.J., O'Dea A.P., Sharma P. Musculoskeletal adverse events associated with adjuvant aromatase inhibitors. J Oncol. 2010;2010:654348. https://doi.org/10.1155/2010/654348.

21. Rocca W.A., Gazzuola-Rocca L., Smith C.Y. et al. Accelerated accumulation of multimorbidity after bilateral oophorectomy: a population-based cohort study. Mayo Clin Proc. 2016;91(11):1577–89. https://doi.org/10.1016/j.mayocp.2016.08.002.

22. Santoro N., Epperson C.N., Mathews S.B. Menopausal symptoms and their management. Endocrinol Metab Clin North Am. 2015;44(3):497– 515. https://doi.org/10.1016/j.ecl.2015.05.001.

23. Zhuang Y., Lyga J. Inflammaging in skin and other tissues – the roles of complement system and macrophage. Inflamm Allergy Drug Targets. 2014;13(3):153–61. https://doi.org/10.2174/1871528113666140522112003

24. Wildman R.P., Colvin A.B., Powell L.H. et al. Associations of endogenous sex hormones with the vasculature in menopausal women: the Study of Women's Health Across the Nation (SWAN). Menopause. 2008;15(3):414–21. https://doi.org/10.1097/gme.0b013e318154b6f5.

25. Soysal P., Stubbs B., Lucato P. et al. Inflammation and frailty in the elderly: A systematic review and meta-analysis. Ageing Res Rev. 2016;31:1–8. https://doi.org/10.1016/j.arr.2016.08.006. Erratum in: Ageing Res Rev. 2017;35:364–5. https://doi.org/10.1016/j.arr.2016.12.007.


Review

For citations:


Gridasova O.S., Solopova A.G., Khizroeva J.Kh., Bitsadze V.O., Ivanov A.E., Galkin V.N., Makatsariya A.D. The role of C3 and C4 complement components in postmenopausal vulvovaginal atrophy with a different clinical history. Obstetrics, Gynecology and Reproduction. 2025;19(6):849–859. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2025.708

Views: 33

JATS XML

ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)