Biomarkers of vascular well-being as risk factors for rosacea in perimenopausal women

Introduction. The article reflects modern literature data on the role of estrogen levels, changes in the homeostasis system, the influence of vasoactive peptides and mediator substances on the course of rosacea. The results of our own study are shown regarding the influence of vascular inflammation biomarkers on the development of rosacea at different periods of menopause. Aim. Determine the role of vascular well-being factors in the development of rosacea in women of perimenopausal age.

Materials and methods. The study included 60 patients of the control group and 97 women with rosacea aged 45–54 years, who were divided into 2 subgroups: (1) premenopausal and (2) postmenopausal period. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, estradiol, vascular endothelial growth factor (VEGF), and fibrin-stabilizing factor (FXIII) in the blood serum were studied.

Results. In the main and control groups, the LH level was within the reference range in the preand postmenopausal periods; in patients with rosacea, it was statistically significantly higher than in healthy women. In the preand postmenopausal periods, estradiol in the control group exceeded the level in patients with rosacea by 1.5 times (p < 0.0001). FSH was significantly higher in patients with rosacea both in the premenopausal period (p < 0.0001) and postmenopause (p = 0.0481). VEGF and FXIII in the main and control groups in healthy women did not depend on the stage of the perimenopausal period, but in rosacea, the median VEGF indicator is 2 times higher than in the control group in the premenopausal period (p < 0.0001), in the postmenopause (p < 0.0001), and the activity of FXIII is statistically significantly higher in the control group both in patients of the premenopausal period (p < 0.0001) and in the postmenopause (p < 0.0001).

Conclusions. In patients with rosacea, the level of gonadotropic hormones is statistically higher than in the group of healthy patients. VEGF and FXIII are significantly increased, which may indicate dysfunction of the vascular endothelium.

1. Drozhdina MB, Bobro VA. Mechanisms of rosacea pathogenesis. A phenotypic approach to therapeutic tactics. Vestnik Dermatologii i Venerologii. 2022;98(5):90–97. (In Russ.) https://doi.org/10.25208/vdv1310.

2. Hampton PJ, Berth-Jones J, Duarte Williamson CE, Hay R, Leslie TA, Porter I et al. British Association of Dermatologists guidelines for the management of people with rosacea 2021. Br J Dermatol. 2021;185(4):725–735. https://doi.org/10.1111/bjd.20485.

3. Zhang J, Jiang P, Sheng L, Liu Y, Liu Y, Li M et al. A Novel Mechanism of Carvedilol Efficacy for Rosacea Treatment: Toll-Like Receptor 2 Inhibition in Macrophages. Front Immunol. 2021;12:609615. https://doi.org/10.3389/fimmu.2021.609615.

4. Spoendlin J, Voegel JJ, Jick SS, Meier CR. A study on the epidemiology of rosacea in the U.K. Br J Dermatol. 2012;167(3):598–605. https://doi.org/10.1111/j.1365-2133.2012.11037.x.

5. Gether L, Overgaard LK, Egeberg A, Thyssen JP. Incidence and prevalence of rosacea: a systematic review and meta-analysis. Br J Dermatol. 2018;179(2):282–289. https://doi.org/10.1111/bjd.16481.

6. Svirshchevskaia EV, Matushevskaia EV, Matushevskaia IuI. Modern questions in rosacea pathogenesis and therapy. Klinicheskaya Dermatologiya i Venerologiya. 2017;16(4):4–13. (In Russ.) https://doi.org/10.17116/klinderma20171644-13.

7. Rainer BM, Fischer AH, Luz Felipe da Silva D, Kang S, Chien AL. Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study. J Am Acad Dermatol. 2015;73(4):604–608. https://doi.org/10.1016/j.jaad.2015.07.009.

8. Kyriakis KP, Palamaras I, Terzoudi S, Emmanuelides S, Michailides C, Pagana G. Epidemiologic aspects of rosacea. J Am Acad Dermatol. 2005;53(5):918–919. https://doi.org/10.1016/j.jaad.2005.05.018.

9. Bansal R, Aggarwal N. Menopausal hot flashes: a concise review. J Midlife Health. 2019;10(1):6–13. https://doi.org/10.4103/jmh.JMH_7_19.

10. Dadaeva VA, Gebekova AU, Drapkina OM. Pathophysiological mechanisms of vascular wall alterations in menopausal women. Profilakticheskaya Meditsina. 2024;27(6):91–97. (In Russ.) https://doi.org/10.17116/profmed20242706191.

11. Santoro N, Sutton-Tyrrell K. The SWAN song: Study of Women’s Health Across the Nation’s Recurring Themes. Obstet Gynecol Clin North Am. 2011;38(3):417–423. https://doi.org/10.1016/j.ogc.2011.05.00118.

12. Mazitova MI, Mardieva RR, Talipova IR, Antropova EYu. Climacteric syndrome. Clinical and epidemiological analysis. Russian Bulletin of Obstetrician-Gynecologist. 2021;21(5):66–72. (In Russ.) https://doi.org/10.17116/rosakush20212105166.

13. Wilkinson HN, Hardman MJ. A role for estrogen in skin ageing and dermal biomechanics. Mech Ageing Dev. 2021;197:111513. https://doi.org/10.1016/j.mad.2021.111513.

14. SenthilKumar G, Katunaric B, Bordas-Murphy H, Sarvaideo J, Freed JK. Estrogen and the Vascular Endothelium: The Unanswered Questions. Endocrinology. 2023;164(6):bqad079. https://doi.org/10.1210/endocr/bqad079.

15. Lu Q, Schnitzler GR, Ueda K, Iyer LK, Diomede OI, Andrade T, Karas RH. ER Alpha Rapid Signaling Is Required for Estrogen Induced Proliferation and Migration of Vascular Endothelial Cells. PLoS ONE. 2016;11(4):e0152807. https://doi.org/10.1371/journal.pone.0152807.

16. Iorga A, Cunningham CM, Moazeni S, Ruffenach G, Umar S, Eghbali M. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol Sex Differ. 2017;8(1):33. https://doi.org/10.1186/s13293-017-0152-8.

17. Yang F, Wang L, Shucheng H, Jiang X. Differences in clinical characteristics of rosacea across age groups: A retrospective study of 840 female patients. J Cosmet Dermatol. 2023;22(3):949–957. https://doi.org/10.1111/jocd.15470.

18. Yang F, Wang L, Jiang X. Clinical characteristics of rosacea in perimenopausal women. Skin Res Technol. 2024;30(1):e13542. https://doi.org/10.1111/srt.13542.

19. Dirschka T, Tronnier H, Fölster-Holst R. Epithelial barrier function and atopic diathesis in rosacea and perioral dermatitis. Br J Dermatol. 2004;150(6):1136–1141. https://doi.org/10.1111/j.1365-2133.2004.05985.x.

20. Olisova OIu, Dodina MI, Kushlinskiĭ NE. The role of vascular endothelial growth factor in pathogenesis of rosacea and its medicamental correction. Klinicheskaya Dermatologiya i Venerologiya. 2012;10(1):49–55. (In Russ.) Available at: https://www.mediasphera.ru/issues/klinicheskayadermatologiya-i-venerologiya/2012/1/downloads/ru/031997-28492012110.

21. Gomaa AH, Yaar M, Eyada MM, Bhawan J. Lymphangiogenesis and angiogenesis in non-phymatous rosacea. J Cutan Pathol. 2007;34(10):748–753. https://doi.org/10.1111/j.1600-0560.2006.00695.x.

22. Tsiskarishvili T, Katsitadze A, Tsiskarishvili NV, Tsiskarishvili NI. The role of some vazoactive peptides in the pathogenesis of early formes of rosacea and the hemostasis system. Georgian Med News. 2018;(Issue):94–97. Available at: https://pubmed.ncbi.nlm.nih.gov/29578433.

23. Pinson IYa, Verkhoglyad IV, Semochkin AV. Current ideas on the etiology and pathogenesis of rosacea. Experimental and Clinical Dermatocos Metology. 2012;(5): 21–24. (In Russ.) Available at: http://elib.fesmu.ru/Article.aspx?id=267658.

24. Kubanov АА, Plakhova XI, Kondrakhina IN, Volkova SV. Pathogenetic substantiation of combination therapy for rosacea. Vestnik Dermatologii i Venerologii. 2023;99(5):13–21. (In Russ.) https://doi.org/10.25208/vdv8538.

25. Гланц С. Медико-биологическая статистика. М.: Практика; 1998. 459 с. Режим доступа: https://medstatistic.ru/articles/glantz.pdf.

26. Korneenkov AA, Ryazantsev SV, Vyazemskaya ЕE. Calculation and interpretation of indicators of informativeness of diagnostic medical technologies. Meditsinskiy Sovet. 2019;(20):45–51. (In Russ.) https://doi.org/10.21518/2079-701X-2019-20-45-51.