About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
Procedure for reviewingReviewers 2023-2024
ISSN 0300-9092 (Print)
ISSN 2412-5679 (Online)
About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
Procedure for reviewingReviewers 2023-2024
Logout
Obstetrics and Gynegology2025№9
Genetic factors in the development...

Genetic factors in the development of endometrial hyperplasia

DOI
https://dx.doi.org/10.18565/aig.2025.121

Churnosov V.I., Ponomarenko I.V., Churnosov M.I.

Belgorod State National Research University, Belgorod, Russia

Endometrial hyperplasia is a gynecological disease characterized by uneven proliferation of the endometrium with an increased gland-to-stroma ratio compared to the normal endometrium. Genetic factors play a significant role in the development of endometrial hyperplasia. The article presents current data on the genetic factors that contribute to this disease. The genetic studies have demonstrated associations with the development of endometrial hyperplasia of certain groups of candidate genes: growth factor genes (TGFß-1, FGFR2, IGF1, EGF), cytokines (TNFα, Ltα, TNFR1, ТNFR2, RANTES, I-TAC, MIP1β, MCP1, SDF1, IL-8, RАNТES), cytochromes (CYP2D6, CYP19A1), lipid metabolism (APOE, FTO), menarche (UGT2B4, LIN28B, ZNF483, LHCGR, FSHB, F13A1, BSX, TMEM38B, 3q13.32, COMT, KISS1, FTO), estrogen receptors (ESR2), oncogenes (AKT1, KRAS, EGFR, PIK3CA, BRAF, NRAS, CTNNB1, PTEN, ARID1A). In addition, a number of studies have shown a link between endometrial hyperplasia and the expression of estrogen receptors, cyclooxygenase-2, and a number of oncogenic microRNAs (miR-18a, miR-210, miR-221, and miR-222). It should be noted that the influence of genetic factors on the development of endometrial hyperplasia has been studied in fragments; the number of associative studies is extremely small, and genome-wide studies of endometrial hyperplasia have not been conducted.
Conclusion: Today, there is a critical need to continue further genetic and epidemiological studies of endometrial hyperplasia.

Authors’ contributions: Churnosov V.I. – literature search and analysis, data summary, writing the text of the manuscript; Ponomarenko I.V. – developing the concept of the article, editing the text of the manuscript; Churnosov M.I. – reviewing, final editing.
Conflicts of interest: Authors declare lack of the possible conflicts of interests.
Funding: The study was supported by the Russian Science Foundation Grant No. 25-25-00034, 
https://rscf.ru/project/25-25-00034/.
For citation: Churnosov V.I., Ponomarenko I.V., Churnosov M.I. 
Genetic factors in the development of endometrial hyperplasia. 
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (9): 40-45 (in Russian)
https://dx.doi.org/10.18565/aig.2025.121

Keywords

endometrial hyperplasia
candidate genes
genetic factors
Full text (in Russian)

References

  1. Wang L., Wei W., Cai M. A review of the risk factors associated with endometrial hyperplasia during perimenopause. Int. J. Womens Health. 2024; 16: 1475-82. https://dx.doi.org/10.2147/IJWH.S481509
  2. Ring K.L., Mills A.M, Modesitt S.C. Endometrial hyperplasia. Obstet. Gynecol. 2022; 140(6): 1061-75. https://dx.doi.org/10.1097/AOG.0000000000004989
  3. Nees L.K., Heublein S., Steinmacher S., Juhasz-Böss I., Brucker S., Tempfer C.B. et al. Endometrial hyperplasia as a risk factor of endometrial cancer. Arch. Gynecol. Obstet. 2022; 306(2): 407-21. https://dx.doi.org/10.1007/s00404-021-06380-5
  4. Chou A.J., Bing R.S., Ding D.C. Endometrial atypical hyperplasia and risk of endometrial cancer. Diagnostics (Basel). 2024; 14(22): 2471. https://dx.doi.org/10.3390/diagnostics14222471
  5. Li Z., Yin J., Liu Y., Zeng F. A risk prediction model for endometrial hyperplasia/ endometrial carcinoma in premenopausal women. Sci. Rep. 2025; 15(1): 1019. https://doi.org/10.1038/s41598-024-83568-0
  6. Подзолкова Н.М., Коренная В.В. Современные представления об этиологии, патогенезе и принципах лечения гиперплазии эндометрия. Акушерство и гинекология. 2021; 8: 192-9. [Podzolkova N.M., Korennaya V.V. Modern ideas about the etiology, pathogenesis and principles of treatment of endometrial hyperplasia. Obstetrics and Gynecology. 2021; (8): 192-9 (in Russian)]. https://dx.doi.org/10.18565/aig.2021.8.192-199
  7. Свиридова Н.И., Ткаченко Л.В., Яхонтова М.А., Гриценко И.А., Максимов С.Н., Пурясева К.А. Гиперпластические процессы эндометрия: современные подходы к диагностике и лечению. Акушерство, гинекология и репродуктология. 2024; 18(1): 83-95. [Sviridova N.I., Tkachenko L.V., Yakhontova M.A., Gritsenko I.A., Maximov S.N., Puryaseva K.A. Endometrial hyperplastic processes: modern approaches to diagnosis and treatment. Obstetrics, Gynecology and Reproduction. 2024; 18(1): 83-95 (in Russian)]. https://dx.doi.org/10.17749/2313-7347/ob.gyn.rep.2023.464
  8. Alsudairi H.N., Alrasheed A.T., Dvornyk V. Estrogens and uterine fibroids: an integrated view. Research Results in Biomedicine. 2021; 7(2): 156-63. https://dx.doi.org/10.18413/2658-6533-2021-7-2-0-6
  9. Yu K., Huang Z.Y., Xu X.L., Li J., Fu X.W., Deng S.L. Estrogen receptor function: impact on the human endometrium. Front. Endocrinol. (Lausanne). 2022; 13: 827724. https://dx.doi.org/10.3389/fendo.2022.827724
  10. Пономаренко И.В., Полоников А.В., Чурносов М.И. Гиперпластические процессы эндометрия: этиопатогенез, факторы риска, полиморфизм генов-кандидатов. Акушерство и гинекология. 2019; 1: 13-8. [Ponomarenko I.V., Polonikov A.V., Churnosov M.I. Endometrial hyperplastic processes: etiopathogenesis, risk factors, polymorphism of candidate genes. Obstetrics and Gynecology. 2019; (1): 13-8 (in Russian)]. https://dx.doi.org/10.18565/aig.2019.1.13-18
  11. Dieudonne A.S., Lambrechts D., Smeets D., Belmans A., Wildiers H., Paridaens R. et al. The rs1800716 variant in CYP2D6 is associated with an increased double endometrial thickness in postmenopausal women on tamoxifen. Ann. Oncol. 2014; 25(1): 90-5. https://dx.doi.org/10.1093/annonc/mdt399
  12. Demakova N.A., Altuchova O.B., Orlova V.S., Pachomov S.P., Krikun E.N. Associations of cytokines genetic polymorphisms with development of endometrial hyperplasia. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2014; 5(5): 1041-5.
  13. Демакова Н.А. Молекулярно-генетические характеристики пациенток с гиперплазией и полипами эндометрия. Научный результат. Медицина и фармация. 2018; 4(2): 26-39. [Demakova N.A. Molecular and genetic characteristics of patients with hyperplasia and endometric polyps. Research Result. Medicine and pharmacy. 2018; 4(2): 26-39 (in Russian)]. https://dx.doi.org/10.18413/2313-8955-2018-4-2-0-4
  14. Ivanova T.I., Krikunova L.I., Ryabchenko N.I., Mkrtchyan L.S., Khorokhorina V.A., Salnikova L.E. Association of the apolipoprotein E 2 allele with concurrent occurrence of endometrial hyperplasia and endometrial carcinoma. Oxid. Med. Cell. Longev. 2015; 2015: 593658. https://dx.doi.org/10.1155/2015/593658
  15. van der Putten L.J.M., van Hoof R., Tops B.B.J., Snijders M.P.L.M., van den Berg-van Erp S.H., van der Wurff A.A.M. et al. Molecular profiles of benign and (pre)malignant endometrial lesions. Carcinogenesis. 2017; 38(3): 329-35. https://dx.doi.org/10.1093/carcin/bgx008
  16. Пономаренко И.В., Полоников А.В., Чурносов М.И. Связь полиморфизма rs4986938 гена ESR2 с развитием гиперплазии эндометрия. Акушерство и гинекология. 2019; 4: 66-72. [Ponomarenko I.V., Polonikov A.V., Churnosov M.I. Association of ESR2 rs4986938 polymorphism with the development of endometrial hyperplasia. Obstetrics and Gynecology. 2019; (4): 66-72 (in Russian)]. https://dx.doi.org/10.18565/aig.2019.4.66-72
  17. Ponomarenko I., Reshetnikov E., Polonikov A., Verzilina I., Sorokina I., Yermachenko A. et al. Candidate genes for age at menarche are associated with endometrial hyperplasia. Front. Gene. 2021; 11: 512940. https://dx.doi.org/10.3389/fgene.2020.512940
  18. Ордиянц И.М., Куулар А.А., Ямурзина А.А., Гусейнова Р.Г., Новгинов Д.С. Генетические и эпигенетические механизмы развития гиперплазии эндометрия у женщин репродуктивного возраста. Акушерство и гинекология: новости, мнения, обучение. 2020; 8(3): 67-70. [Ordiyants I.M., Kuular A.A., Yamurzina A.A., Huseynova R.G., Novginov D.S. Genetic and epigenetic mechanisms for the development of endometrial hyperplasia in women of reproductive age. Obstetrics and Gynecology: News, Opinions, Training. 2020; 8(3): 67-70 (in Russian)]. https://dx.doi.org/10.24411/2303-9698-2020-13009
  19. Фаткуллин И.Ф., Габидуллина Р.И., Смирнова Г.А., Нухбала Ф.Р., Валеева Е.В., Орлова Ю.И., Шакиров А.А. Ассоциация полиморфизма RS2414098 гена CYP19A1 с риском развития гиперплазии эндометрия. Акушерство и гинекология. 2020; 2: 125-30. [Fatkullin I.F., Gabidullina R.I., Smirnova G.A., Nukhbala F.R., Valeeva E.V., Orlova Yu.I., Shakirov A.A. The association between rs2414098 polymorphism of the CYP19A1 gene and the risk of developing endometrial hyperplasia. Obstetrics and Gynecology. 2020; (2): 125-30 (in Russian)]. https://dx.doi.org/10.18565/aig.2020.2.125-130
  20. Алтухова О.Б., Радзинский В.Е., Полякова И.С., Чурносов М.И. Роль генов факторов роста в развитии миомы матки в сочетании с гиперплазией эндометрия. Акушерство и гинекология. 2021; 4: 104-10. [Altukhova O.B., Radzinsky V.E., Polyakova I.S., Churnosov M.I. The role of growth factor genes in the development of uterine fibroids combined with endometrial hyperplasia. Obstetrics and Gynecology. 2021; (4): 104-10 (in Russian)]. https://dx.doi.org/10.18565/aig.2021.4.104-110
  21. Алтухова О.Б., Радзинский В.Е., Полякова И.С., Сиротина С.С., Батлуцкая И.В., Орлова В.С., Ефремова О.А., Чурносов М.И. Роль генов хемокинов в развитии внутреннего генитального эндометриоза в сочетании с гиперпластическими процессами эндометрия. Акушерство и гинекология. 2022; 8: 76-84. [Altukhova O.B., Radzinsky V.E., Polyakova I.S., Sirotina S.S., Batlutskaya I.V., Orlova V.S., Efremova O.A., Churnosov M.I. The role of chemokine genes in the development of adenomyosis with concurrent endometrial hyperplastic processes. Obstetrics and Gynecology. 2022; (8): 76-84 (in Russian)]. https://dx.doi.org/10.18565/aig.2022.8.76-84
  22. Li L., Yue P., Song Q., Yen T.T., Asaka S., Wang T.L. et al. Genome-wide mutation analysis in precancerous lesions of endometrial carcinoma. J. Pathol. 2021; 253(1): 119-28. https://dx.doi.org/10.1002/path.5566
  23. Weng C.H., Wu K.Y., Wang C.J., Huang H.J., Tsai C.L., Lin C.Y. et al. Massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical and non-atypical endometrial hyperplasia. Front. Med. (Lausanne). 2022; 9: 1090788. https://dx.doi.org/10.3389/fmed.2022.1090788
  24. Ponomarenko M.S., Reshetnikov E.A., Churnosova M.M., Reshetnikova Y.N., Churnosov V.I., Ponomarenko I.V. Comorbidity and syntropy of benign proliferative diseases of the female reproductive system: non-genetic, genetic, and epigenetic factors (review). Research Results in Biomedicine. 2023; 9(4): 544-56. https://dx.doi.org/10.18413/2658-6533-2023-9-4-0-9
  25. Tsyndrenko N., Lyndіn M., Sikora K., Wireko A.A., Abdul-Rahman T., Hyriavenko N. et al. ER and COX2 expression in endometrial hyperplasia processes. Medicine (Baltimore). 2023; 102(33): e34864. https://dx.doi.org/10.1097/MD.0000000000034864
  26. Tsyndrenko N.L., Lyndin M.S., Sikora K.O., Shamray A.V., Tsepochko D.G., Lyndina Yu.M. et al. Clinical-morphological and genetic characteristics of endometrial hyperplastic processes. Azerbaijan Medical Journal. 2024; 3: 75-80. https://dx.doi.org/10.34921/amj.2024.3.013
  27. Чурносов В.И., Пономаренко И.В., Пономаренко М.С., Чурносов М.И. Анализ генетических факторов риска развития гиперплазии эндометрия у женщин с избыточной массой тела и ожирением. Акушерство и гинекология. 2025; 5: 58-65. [Churnosov V.I., Ponomarenko I.V., Ponomarenko M.S., Churnosov M.I. Analysis of genetic risk factors for endometrial hyperplasia in overweight and obese women. Obstetrics and Gynecology. 2025; (5): 58-65 (in Russian)]. https://dx.doi.org/10.18565/aig.2025.39
  28. Чурносов В.И. Ассоциации полиморфных локусов генов-кандидатов с уровнем половых гормонов у больных гиперплазией эндометрия. Научные результаты биомедицинских исследований. 2025; 11(2): 243-62. [Churnosov VI. Associations of polymorphic loci of candidate genes with the level of sex hormones in patients with endometrial hyperplasia. Research Results in Biomedicine. 2025; 11(2): 243-62 (in Russian)]. https://dx.doi.org/10.18413/2658-6533-2025-11-2-0-3
  29. Ruth K.S., Beaumont R.N., Tyrrell J., Jones S.E., Tuke M.A., Yaghootkar H. et al. Genetic evidence that lower circulating FSH levels lengthen menstrual cycle, increase age at menopause and impact female reproductive health. Hum. Reprod. 2016; 31(2): 473-81. https://dx.doi.org/10.1093/humrep/dev318
  30. Gudjonsson A., Gudmundsdottir V., Axelsson G.T., Gudmundsson E.F., Jonsson B.G., Launer L.J. et al. A genome-wide association study of serum proteins reveals shared loci with common diseases. Nat. Commun. 2022; 13(1): 480. https://dx.doi.org/10.1038/s41467-021-27850-z
  31. Ruth K.S., Day F.R., Tyrrell J., Thompson D.J., Wood A.R., Mahajan A. et al. Using human genetics to understand the disease impacts of testosterone in men and women. Nat. Med. 2020; 26(2): 252-8. https://dx.doi.org/10.1038/s41591-020-0751-5
  32. Haas C.B., Hsu L., Lampe J.W., Wernli K.J., Lindström S. Cross-ancestry Genome-wide Association Studies of Sex Hormone Concentrations in Pre- and Postmenopausal Women. Endocrinology. 2022; 163(4): bqac020. https://dx.doi.org/10.1210/endocr/bqac020
  33. Leinonen J.T., Mars N., Lehtonen L.E., Ahola-Olli A., Ruotsalainen S., Lehtimäki T. et al. Genetic analyses implicate complex links between adult testosterone levels and health and disease. Commun. Med. 2023; 3(1): 4. https://dx.doi.org/10.1038/s43856-022-00226-0
  34. Головченко И.О. Генетические детерминанты уровня половых гормонов у больных эндометриозом. Научные результаты биомедицинских исследований. 2023; 9(1): 5-21. [Golovchenko I.O. Genetic determinants of sex hormone levels in endometriosis patients. Research Results in Biomedicine. 2023; 9(1): 5-21 (in Russian)]. https://dx.doi.org/10.18413/2658-6533-2023-9-1-0-1
  35. Пономарева Т.А. Генетические варианты глобулина, связывающего половые гормоны, и гормональный профиль больных генитальным эндометриозом. Научные результаты биомедицинских исследований. 2025; 11(1): 75-90. [Ponomareva T.A. Genetic variants of sex hormone-binding globulin and hormonal profile in patients with genital endometriosis. Research Results in Biomedicine. 2025; 11(1): 75-90 (in Russian)]. https://dx.doi.org/10.18413/2658-6533-2025-11-1-0-4
  36. Gotoh O., Sugiyama Y., Tonooka A., Kosugi M., Kitaura S., Minegishi R. et al. Genetic and epigenetic alterations in precursor lesions of endometrial endometrioid carcinoma. J. Pathol. 2024; 263(3): 275-87. https://dx.doi.org/10.1002/path.6278

Received 06.05.2025

Accepted 20.08.2025

About the Authors

Vladimir I. Churnosov, PhD student at the Department of Biomedical Disciplines, Belgorod State National Research University, 308015, Russia, Belgorod, Pobedy str., 85, +7(4722)30-13-83, vchurnosov@yandex.kz, https://orcid.org/0009-0007-8519-4594
Irina V. Ponomarenko, Dr. Med. Sci., Professor at the Department of Medical and Biological Disciplines, Belgorod State National Research University, 308015, Russia, Belgorod, Pobedy str., 85, +7(4722)30-13-83, ponomarenko_i@bsuedu.ru, https://orcid.org/0000-0002-5652-0166
Mikhail I. Churnosov, Dr. Med. Sci., Head of the Department of Medical and Biological Disciplines, Belgorod State National Research University, 308015, Russia, Belgorod, Pobedy str., 85, +7(4722)30-13-83, churnosov@bsuedu.ru, https://orcid.org/0000-0003-1254-6134
Corresponding author: Irina V. Ponomarenko, ponomarenko_i@bsuedu.ru

Similar Articles

№6 / 2025
Subanova G.A., Subanova N.A., Askerov A.A., Yrysbaev E.Y., Dzhumaeva L.M., Yrysbaev A.Y.
Hormone-dependent diseases of the pelvic organs in women over 35 years of age
№11 / 2021
Chernukha G.E., Tabeeva G.I., Rshtuni S.D., Mashaeva R.I., Chernykh V.B., Marchenko L.A.
Genes involved in premature ovarian failure
№10 / 2022
Rshtuni S.D., Chernukha G.E., Bystritskiy A.A., Tabeeva G.I., Krasheninnikova R.V., Marchenko L.A.
BRCA1 pathogenic variants in women with premature ovarian failure
№3 / 2025
Khashukoeva A.Z., Agaeva M.I., Agaeva Z.A., Lobacheva Yu.I., Smagina Yu.A.
Characteristics of Buserelin-depo use in the treatment for comorbid pathologies of reproductive organs
№5 / 2025
Churnosov V.I., Ponomarenko I.V., Ponomarenko M.S., Churnosov M.I.
Analysis of genetic risk factors for endometrial hyperplasia in overweight and obese women
By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.