Preview

Problems of Endocrinology

Advanced search

Immunological status in patients with amenorrhea (literature review)

https://doi.org/10.14341/probl13456

Abstract

Amenorrhea is a common symptom of a whole range of nosologies among women of reproductive age, which can accompany any endocrinopathy in the stage of decompensation. In all the diversity of various links in the pathogenesis of reproductive disorders, the problem of immunopathology remains a little aside, however, the significance of these disorders is underestimated. This publication provides an overview of immune system abnormalities in a women with amenorrhea. As is known, in polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI), one of the clinical manifestations is amenorrhea. On the one hand, these nosologies differ significantly from each other in etiology, pathogenesis and approaches to therapy, and on the other hand, they have a common similarity, manifested by immunological disorders. The article provides information about the immune status of patients with PCOS and POI. Works devoted to various disorders in the immune system, pathologies of humoral and cellular immunity, which in the future may serve as the key to the development of new and non-standard methods of treating such socially significant diseases, are analyzed. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The choice of sources was prioritized for the period from 2018 to 2024.

About the Authors

Y. S. Absatarova
Endocrinology Research Centre Russia
Russian Federation

Yulia S. Absatarova, MD, PhD

Moscow



Y. S. Evseeva
Endocrinology Research Centre Russia
Russian Federation

Yulia S. Evseeva

11 Dm. Ulyanova street, 117036 Moscow



E. N. Andreeva
Endocrinology Research Centre Russia; Russian university of medicine
Russian Federation

Elena N. Andreeva, MD, PhD, professor

Moscow



Z. T. Zuraeva
Endocrinology Research Centre Russia
Russian Federation

Zamira T. Zuraeva, MD

Moscow



E. V. Sheremetyeva
Endocrinology Research Centre Russia
Russian Federation

Ekaterina V. Sheremetyeva, MD, PhD

Moscow



O. R. Grigoryan
Endocrinology Research Centre Russia
Russian Federation

Olga R. Grigoryan, MD, PhD, professor

Moscow



R. K. Mikheev
Endocrinology Research Centre Russia
Russian Federation

Robert K. Mikheev, MD, resident

Moscow



References

1. Sandakova ЕА, Zhukovskaya IG. Normogonadotropic menstrual function disorders in reproductive period. Clinical lecture. Perm Medical Journal. 2022;39(6):38-53. (in Russ.)] doi: https://doi.org/10.17816/pmj39638%5

2. Rossijskoe obshhestvo akusherov-ginekologov. Klinicheskie rekomendacii. Amenoreja. Moscow: Ministerstvo zdravoohranenija RF; 2021. (In Russ.)

3. Yurkova AA. Osnovy kletochnogo immuniteta. International Journal of Humanities and Natural Sciences. 2021:5(2):66-68. (in Russ.)] doi: https://doi.org/10.24412/2500-1000-2021-5-2-66-68

4. Li Z, Peng A, Feng Y, et al. Detection of T lymphocyte subsets and related functional molecules in follicular fluid of patients with polycystic ovary syndrome. Scientific reports. 2019;9(1):6040. doi: https://doi.org/10.1038/s41598-019-42631-x

5. Forsyth KS, Jiwrajka N, Lovell CD, et al. The conneXion between sex and immune responses. Nature reviews. Immunology. 2024. Published online. doi: https://doi.org/10.1038/s41577-024-00996-9

6. Kissick HT, Sanda MG, Dunn LK, et al. Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(27):9887-9892. doi: https://doi.org/10.1073/pnas.1402468111

7. Roved J, Westerdahl H, Hasselquist D. Sex differences in immune responses: Hormonal effects, antagonistic selection, and evolutionary consequences. Hormones and behavior. 2017;88:95–105. doi: https://doi.org/10.1016/j.yhbeh.2016.11.017

8. Lima PDA, Nivet AL, Wang Q, et al. Polycystic ovary syndrome: possible involvement of androgen-induced, chemerin-mediated ovarian recruitment of monocytes/ macrophages. Biology of reproduction. 2018;99:838–852. doi: https://doi.org/10.1093/biolre/ioy096

9. Hases L, Archer A, Williams C. ERβ and inflammation. Advances in experimental medicine and biology. 2022;1390:213–25. doi: https://doi.org/10.1007/978-3-031-11836-4_12

10. Cutolo M, Sulli A, Straub RH. Estrogen metabolism and autoimmunity. Autoimmunity reviews. 2012;11(6-7):A460–A464. doi: https://doi.org/10.1016/j.autrev.2011.11.014

11. Straub RH. The complex role of estrogens in inflammation. Endocrine reviews. 2007;28(5):521–574. doi: https://doi.org/10.1210/er.2007-0001

12. Chakraborty B, Byemerwa J, Krebs T, et al. Estrogen Receptor Signaling in the Immune System. Endocrine Reviews. 2023;44(1): 117–141. doi: https://doi.org/10.1210/endrev/bnac017

13. Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome. Nature reviews. Disease primers. 2016;2:16057. doi: https://doi.org/10.1038/nrdp.2016.57

14. Sindrom polikistoznyh yaichnikov. Klinicheskie rekomendacii. M.: Ministerstvo zdravoohraneniya Rossijskoj federacii.2021. (In Russ.)

15. Rudnicka E, Suchta K, Grymowicz M, et al. Chronic low Grade inflammation in Pathogenesis of PCOS. International journal of molecular sciences. 2021;22(7):3789. doi: https://doi.org/10.3390/ijms22073789

16. Zhai Y, Pang Y. Systemic and ovarian inflammation in women with polycystic ovary syndrome. Journal of reproductive immunology. 2022;151:103628. doi: https://doi.org/10.1016/j.jri.2022.103628

17. Bahceci M, Gokalp D, Bahceci S, et al. The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults? Journal of endocrinological investigation. 2007;30(3):210–214. doi: https://doi.org/10.1007/BF03347427

18. Gomez JMD, VanHise K, Stachenfeld N, et al. Subclinical cardiovascular disease and polycystic ovary syndrome. Fertility and sterility. 2022;117(5):912–923. doi: https://doi.org/10.1016/j.fertnstert.2022.02.028

19. Salamun V, Rizzo M, Lovrecic L, et al. The Endometrial Transcriptome of Metabolic and Inflammatory Pathways during the Window of Implantation Is Deranged in Infertile Obese Polycystic Ovarian Syndrome Women. Metabolic syndrome and related disorders. 2022;20(7):384–394. doi: https://doi.org/10.1089/met.2021.0149

20. Wang J, Teng F, Wu Q, Wu Y, Hu L. Relationship between proinflammatory cytokines and clomiphene resistance in patients with polycystic ovary syndrome. Annals of palliative medicine. 2021;10(11):11884-11890. doi: https://doi.org/10.21037/apm-21-3031

21. Abraham Gnanadass S, Divakar Prabhu Y, Valsala Gopalakrishnan A. Association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): an update. Archives of gynecology and obstetrics. 2021;303(3):631-643. doi: https://doi.org/10.1007/s00404-020-05951-2

22. Yang Y, Xia J, Yang Z, et al. The abnormal level of HSP70 is related to Treg/Th17 imbalance in PCOS patients. Journal of ovarian research. 2021;14(1):155. doi: https://doi.org/10.1186/s13048-021-00867-0

23. Hu C, Pang B, Ma Z, Yi H. Immunophenotypic profiles in polycystic ovary syndrome. Mediators of inflammation. 2020;2020:5894768. doi: https://doi.org/10.1155/2020/5894768

24. Figueroa F, Motta A, Acosta M, et al. Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis. Reproduction (Cambridge, England). 2015;150(5):437–448. doi: https://doi.org/10.1530/REP-15-0216

25. Shang J, Wang S, Wang A, et al. Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment. Reproductive biology and endocrinology. 2024;22(1):11. doi: https://doi.org/10.1186/s12958-023-01183-6

26. Menten P, Wuyts A, Van Damme J. Macrophage inflammatory protein-1. Cytokine & growth factor reviews. 2002;13:455–81. doi: https://doi.org/10.1016/S1359-6101(02)00045-X

27. Mukaida N, Sasaki S-I, Baba T. CCL4 signaling in the Tumor Microenvironment. Advances in experimental medicine and biology. 2020;1231:23–32. doi: https://doi.org/10.1007/978-3-030-36667-4_3

28. Sarapik A, Velthut A, Haller-Kikkatalo K, et al. Follicular proinflammatory cytokines and chemokines as markers of IVF success. Clinical & developmental immunology. 2012;2012:606459. doi: https://doi.org/10.1155/2012/606459

29. Jin L, Ren L, Lu J, et al. CXCL12 and its receptors regulate granulosa cell apoptosis in PCOS rats and human KGN tumor cells. Reproduction. 2021;161:145–57. doi: https://doi.org/10.1530/REP-20-0451

30. Aru N, Yang C, Chen Y, Liu J. Causal association of immune cells and polycystic ovarian syndrome: a Mendelian randomization study. Frontiers in endocrinology. 2023;14:1326344. doi: https://doi.org/10.3389/fendo.2023.1326344

31. Ascani A, Torstensson S, Risal S, et al. The role of B cells in immune cell activation in polycystic ovary syndrome. eLife. 2023;12:e86454. doi: https://doi.org/10.7554/eLife.86454.sa2

32. Pavlasova G, Mraz M. The regulation and function of CD20: an «enigma» of B-cell biology and targeted therapy. Haematologica. 2020;105(6):1494–506. doi: https://doi.org/10.3324/haematol.2019.243543

33. Somerset D, Zheng Y, Kilby M, et al. Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset. Immunology. 2004;112(1):38–43. doi: https://doi.org/10.1111/j.1365-2567.2004.01869.x

34. Cros J, Cagnard N, Woollard K, et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity. 2010;33(3):375–86. doi: https://doi.org/10.1016/j.immuni.2010.08.012

35. Zhang B, Qi X, Zhao Y, et al. Elevated CD14CD16 monocytes in hyperhomocysteinemia-associated insulin resistance in polycystic ovary syndrome. Reproductive sciences (Thousand Oaks, Calif.). 2018;25(12):1629–36. doi: https://doi.org/10.1177/1933719118756772

36. Ford EA, Beckett EL, Roman SD, et al. Advances in human primordial follicle activation and premature ovarian insufficiency. Reproduction. 2020; 159(1): R15-R29. doi: https://doi.org/10.1530/REP-19-0201

37. Kravchenko EN, Vorontsova MS. Prezhdevremennaya nedostatochnost’ yaichnikov, sovremennyi vzglyad na problemu. Mat’ i Ditya v Kuzbasse. 2022;88(1):4-10. (in Russ.)] doi: https://doi.org/10.24412/2686-7338-2022-1-4-10

38. Yang X, Gilman-Sachs A, Kwak-Kim J. Ovarian and endometrial immunity during the ovarian cycle. Journal of reproductive immunology. 2019;133:7–14. doi: https://doi.org/10.1016/j.jri.2019.04.001

39. Huang Y, Hu C, Ye H, et al. Inflamm-Aging: A new mechanism affecting premature ovarian insufficiency. Journal of immunology research. 2019;2019:8069898. doi: https://doi.org/10.1155/2019/8069898

40. Liu P, Zhang X, Hu J, et al. Dysregulated cytokine profile associated with biochemical premature ovarian insufficiency. American journal of reproductive immunology. 2020;84(4):e13292. doi: https://doi.org/10.1111/aji.13292

41. Jiao X, Zhang X, Li N, et al. Treg deficiency-mediated T(H) 1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells. Clinical and translational medicine. 2021;11(6):e448. doi: https://doi.org/10.1002/ctm2.448

42. Kaipia A, Chun SY, Eisenhauer K, Hsueh AJ. Tumor necrosis factoralpha and its second messenger, ceramide, stimulate apoptosis in cultured ovarian follicles. Endocrinology. 1996;137(11):4864–4870. doi: https://doi.org/10.1210/endo.137.11.8895358

43. Liu D, Guan X, Liu W, et al. Identification of transcriptome characteristics of granulosa cells and the possible role of UBE2C in the pathogenesis of premature ovarian insufficiency. Journal of ovarian research. 2023;16(1):203. doi: https://doi.org/10.1186/s13048-023-01266-3

44. Martins TS, Fonseca BM, Rebelo I. The role of macrophages phenotypes in the activation of resolution pathways within human granulosa cells. Reproductive biology and endocrinology. 2022;20(1):116. doi: https://doi.org/10.1186/s12958-022-00983-6

45. Zhang C, Yu D, Mei Y, et al. Single-cell RNA sequencing of peripheral blood reveals immune cell dysfunction in premature ovarian insufficiency. Frontiers in endocrinology. 2023;14:1129657. doi: https://doi.org/10.3389/fendo.2023.1129657

46. Joo, Na-Rae et al. “TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53.” Biochemical and biophysical research communications. vol. 664 (2023): 128-135. doi: https://doi.org/10.1016/j.bbrc.2023.04.113

47. Szeliga A, Calik-Ksepka A, Maciejewska-Jeske M, et al. Autoimmune Diseases in Patients with Premature Ovarian InsufficiencyOur Current State of Knowledge. Int J Mol Sci. 2021;22(5):2594. doi: https://doi.org/10.3390/ijms22052594

48. Jiao X, Zhang X, Li N, et al. Treg deficiency-mediated T(H) 1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells. Clinical and translational medicine. 2021;11(6):e448. doi: https://doi.org/10.1002/ctm2.448

49. Dominguez-Villar M, Hafler DA. Regulatory T cells in autoimmune disease. Nat Immunol. 2018;19:665–73. doi: https://doi.org/10.1038/s41590-018-0120-4

50. Kobayashi M, Nakashima A, Yoshino O, et al. Decreased effector regulatory T cells and increased activated CD4(+) T cells in premature ovarian insufficiency. Am J Reprod Immunol. 2019;81:e13125. doi: https://doi.org/10.1111/aji.13125

51. Xiong J, Tan R, Wang W, et al. Evaluation of CD4(+)CD25(+) FOXP3(+) regulatory T cells and FOXP3 mRNA in premature ovarian insufficiency. Climacteric. 2020;23:267–72. doi: https://doi.org/10.1080/13697137.2019.1703938

52. Košir Pogačnik R, Meden Vrtovec H, Vizjak A, Uršula Levičnik A, Slabe N, Ihan A. Possible role of autoimmunity in patients with premature ovarian insufficiency. Int J Fertil Steril. 2014;7(4):281-290

53. Wang Y, Zhuo A, Yang Y, et al. Regulatory T Cells Overexpressing Peli1 Show Better Efficacy in Repairing Ovarian Endocrine Function in Autoimmune Premature Ovarian Insufficiency. Lab Invest. 2023;103(2):100005. doi: https://doi.org/10.1016/j.labinv.2022.100005

54. Liu J, Huang X, Hao S, et al. Peli1 negatively regulates noncanonical NF-kB signaling to restrain systemic lupus erythematosus. Nat Commun. 2018;9(1):1e13.doi: https://doi.org/10.1038/s41467-018-03530-3

55. Li X, Xie J, Wang Q, Cai H, Xie C, Fu X. miR-21 and Pellino-1 Expression Profiling in Autoimmune Premature Ovarian Insufficiency. J Immunol Res. 2020;2020:3582648. doi: https://doi.org/10.1155/2020/3582648

56. Rybkina VL, Adamova GV, Oslina DS. The role of cytokines in the pathogenesis of malignant neoplasms. Сибирский научный медицинский журнал. 2023;43(2):15-28. (In Russ.)] doi: https://doi.org/10.18699/SSMJ20230202

57. Yang H, Pang H, Miao C. Ovarian IL-1α and IL-1β levels are associated with primary ovarian insufficiency. Int J Clin Exp Pathol. 2018;11:4711-4717

58. Sun S, Chen H, Zheng X, et al. Analysis on the level of IL-6, IL-21, AMH in patients with auto-immunity premature ovarian failure and study of correlation. Exp Ther Med. 2018;16:3395-3398. doi: https://doi.org/10.3892/etm.2018.6592

59. Zhang W, Xu S, Zhang R, et al. The TH 22-mediated IL-22 deficiency associated with premature ovarian insufficiency. Am J Reprod Immunol. 2023;89(4):e13685. doi: https://doi.org/10.1111/aji.13685


Supplementary files

Review

For citations:


Absatarova Y.S., Evseeva Y.S., Andreeva E.N., Zuraeva Z.T., Sheremetyeva E.V., Grigoryan O.R., Mikheev R.K. Immunological status in patients with amenorrhea (literature review). Problems of Endocrinology. 2024;70(6):118-126. (In Russ.) https://doi.org/10.14341/probl13456

Views: 458


ISSN 0375-9660 (Print)
ISSN 2308-1430 (Online)