Elevated estrogen receptor beta and oxidative stress in postmenopausal women with ovarian cancer
DOI:
https://doi.org/10.15584/ejcem.2025.4.10Keywords:
β-estrogen receptors, hormonal disorders, ovarian cancer, oxidative stress, postmenopausalAbstract
Introduction and aim. Ovarian cancer in postmenopausal women is associated with hormonal dysregulation and oxidative stress. This study investigates the relationship between estrogen receptor beta (ERβ), selected reproductive hormones, and oxidative stress markers in women with ovarian cancer compared to healthy controls. To our knowledge, this is one of the first studies to evaluate these parameters in an integrated way, offering new insights into the pathophysiological mechanisms underlying postmenopausal ovarian cancer.
Material and methods. Blood samples were collected from 45 postmenopausal women with ovarian cancer immediately after diagnosis to be compared with 45 healthy women. ERβ and some hormones were evaluated using an enzyme-linked immunosorbent assay. Chemiluminescence imunoassays and miniVIDAS, while spectrophotometric methods were used to evaluate variables associated with oxidative stress.
Results. The results show a significant increase in beta estrogen receptor values for women with ovarian cancer 12.69±1.79 ng/mL, p<0.001 compared to healthy women 0.47±0.06 ng/mL. Furthermore, a significant increase was observed in the values of each estrogen (E2) 18.4±2.19 pg/mL vs. 16.20±3.45 pg/mL, p=0.001, anti-Müllerian hormone (AMH) 15.56±2.88 pmol/L vs. 1.22±0.29 pmol/L, p<0.001, and total oxidant status 2.93±0.63 µmol/L vs. 0.65±0.09 µmol/L, p<0.001. On the contrary, a significant decrease in total antioxidant capacity 3.22±0.72 mmol/L vs. 10.04±1.50 mmol/L, p<0.001. The results also show a positive correlation between the values of total oxidants and the hormones studied, compared to the negative correlation with total antioxidants.
Conclusion. The significant increase in the values of ERβ as well as the estrogen hormone that may be derived from adipose tissue in women with ovarian cancer in the postmenopausal stage, has multiple effects, for example, by altering some hormones such as progesterone, dehydroepiandrosterone sulfate, testosterone, and AMH. These hormonal disturbances resulting from granulosa cell tumors play a role in increasing the metabolic rate and therefore increasing the oxidative stress of cells.
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References
Li Y, Song W, Gao P, et al. Global, regional, and national burden of breast, cervical, uterine, and ovarian cancer and their risk factors among women from 1990 to 2021, and projections to 2050: findings from the global burden of disease study 2021. BMC Cancer. 2025;25(1):330. doi: 10.1186/s12885-025-13741-9
Subramanian DN, Zethoven M, Pishas KI, et al. Assessment of candidate high-grade serous ovarian carcinoma predisposition genes through integrated germline and tumour sequencing. NPJ Genomic Med. 2025;10(1):1. doi: 10.1038/s41525-024-00447-3
Punzón-Jiménez P, Lago V, Domingo S, Simón C, Mas A. Molecular management of high-grade serous ovarian carcinoma. Int J Mol Sci. 2022;23(22):1-30. doi: 10.3390/ijms232213777
Zhang Q, Li Y, Li J, Ma J, Li M, Guo LH. A Fluorescence Biosensor with a Dual-function DNA Probe Targeting the Activated Estrogen Receptor for Estrogenic Activity Evaluation. Environ Res. 2025;273(1):121-163. doi: 10.1016/j.envres.2025.121163
Lutz PB, Coombs WR, Bayse CA. Determination of Structural Factors Contributing to Protection of Zinc Fingers in Estrogen Receptor α through Molecular Dynamic Simulations. J Phys Chem B. 2025;129(8):2226-2234. doi: 10.1021/acs.jpcb.4c05730
Bhatia N, Kumar S, Goyal LD, Thareja S. Optimizing selective estrogen receptor degraders for anticancer drug development. Future Med Chem. 2025;17(6):637-640. doi: 10.1080/17568919.2025.2467615
Clusan L, Ferrière F, Flouriot G, Pakdel F. A basic review on estrogen receptor signaling pathways in breast cancer. Int J Mol Sci. 2023;24(7):6834. doi: 10.3390/ijms24076834
Ünal Ç, Ordu Ç, Özmen T, et al. Evaluation of Anti-Mullerian Hormone Levels, Antral Follicle Counts, and Mean Ovarian Volumes in Chemotherapy-Induced Amenorrhea among Breast Cancer Patients: A Prospective Clinical Study. Curr Oncol. 2023;30(10):9217-9229. doi: 10.3390/curroncol30100666
Jovičić S, Plebani M. Biomarkers of menopause. Arch Pharm. 2025;75(1):1-14. doi: 10.5937/arhfarm75-55314
Cetin N, Koca D. Anti‐Müllerian Hormone Concentrations Can Be Reliably Determined by a Single Measurement, Irrespective of Cycle, in Synchronised Ewes During Non‐Breeding Season. Reprod Domest Anim. 2025;60(2):1-6. doi: 10.1111/rda.70010
Karkanaki A, Vosnakis C, Panidis D. The clinical significance of anti-Müllerian hormone evaluation in gynecological endocrinology. Hormones. 2011;10(2):95-103.
Mukherjee S, Nag S, Mukerjee N, et al. Unlocking exosome-based theragnostic signatures: deciphering secrets of ovarian cancer metastasis. ACS Omega. 2023;8(40):36614-36627. doi: 10.1021/acsomega.3c02837
Rajan N, Debnath S, Perveen K, et al. Optimizing hybrid vigor: a comprehensive analysis of genetic distance and heterosis in eggplant landraces. Front Plant Sci. 2023;14(1):1238870. doi: 10.3389/fpls.2023.1238870
Tufan AN, Çelik SE, Özyürek M, Güçlü K, Apak R. Direct measurement of total antioxidant capacity of cereals: QUENCHER-CUPRAC method. Talanta. 2013;108(1):136-142. doi: 10.1016/j.talanta.2013.02.061
Kiesel L, Eichbaum C, Baumeier A, Eichbaum M. Obesity epidemic—the underestimated risk of endometrial cancer. Cancers (Basel). 2020;12(12):3860. doi: 10.3390/cancers12123860
Leeners B, Geary N, Tobler PN, Asarian L. Ovarian hormones and obesity. Hum Reprod Update. 2017;23(3):300-321. doi: 10.1093/humupd/dmw045
Dallal CM, Lacey J V, Pfeiffer RM, et al. Estrogen metabolism and risk of postmenopausal endometrial and ovarian cancer: the B∼ FIT cohort. Horm Cancer. 2016;7(1):49-64. doi: 10.1007/s12672-015-0237-y
Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol. 2019;70(6):111-113. doi: 10.1038/ ncomms15840
Birgersson M, Indukuri R, Antonson P, Nalvarte I, Archer A, Williams C. ERβ in granulosa cell tumors and its clinical potential. Endocrinology. 2023;164(6):bqad063. doi: 10.1210/endocr/bqad063
Ciucci A, Ferrandina G, Mascilini F, et al. Estrogen receptor β: Potential target for therapy in adult granulosa cell tumors? Gynecol Oncol. 2018;150(1):158-165. doi: 10.1016/j.ygyno.2018.05.013
Cluzet V, Devillers MM, Petit F, et al. Estradiol promotes cell survival and induces Greb1 expression in granulosa cell tumors of the ovary through an ERα‐dependent mechanism. J Pathol. 2022;256(3):335-348. doi: 10.1002/path.5843
Gao X, Yi Y, Lv J, et al. Low RNA stability signifies strong expression regulatability of tumor suppressors. Nucleic Acids Res. 2023;51(21):11534-11548. doi: 10.1093/nar/gkad838
Khan D, Ansar Ahmed S. The immune system is a natural target for estrogen action: opposing effects of estrogen in two prototypical autoimmune diseases. Front Immunol. 2016;6(1):1-8. doi: 10.3389/fimmu.2015.00635
Zwimpfer TA, Tal O, Geissler F, et al. Low grade serous ovarian cancer–a rare disease with increasing therapeutic options. Cancer Treat Rev. 2023;112(1):102497. doi: 10.1016/j.ctrv.2022.102497
Wang G, Zhang R, Li C, Chen A. Characteristics and outcomes analysis of ovarian Sertoli–Leydig cell tumors (SLCTs): analysis of 15 patients. J Ovarian Res. 2021;14(1):150. doi: 10.1186/s13048-021-00909-7
Akman L, Ertas IE, Gokcu M, et al. Ovarian sertoli–leydig cell tumors: A multicenter long-term clinicopathological analysis of 27 patients. J Cancer Res Ther. 2016;12(1):290-294. doi: 10.4103/0973-1482.158037
Nef J, Huber DE. Ovarian Sertoli–Leydig cell tumours: A systematic review of relapsed cases. Eur J Obstet Gynecol Reprod Biol. 2021;263(1):261-274. doi: 10.1016/j.ejogrb.2021.06.036
Durlinger A, Visser J, Themmen A. Regulation of ovarian function: the role of anti-Mullerian hormone. Reproduction. 2002;124(1):601-609.
Friedlander ML, Anderson L, Lee YC. Controversies in the management of ovarian granulosa cell and Sertoli-Leydig cell tumors. Int J Gynecol Cancer. 2025;35(3):101668. doi: 10.1016/j.ijgc.2025.101668
Xu S, Hu D, Ye Y, Mu Y, Xiong Y, Zhang Y. Identification of serum small non-coding RNA as biomarkers for endometrial receptivity. Genomics. 2025;117(2):111002. doi: 10.1016/j.ygeno.2025.111002
de Vet A, Laven JSE, de Jong FH, Themmen APN, Fauser BCJM. Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril. 2002;77(2):357-362. doi: 10.1016/S0015-0282(01)02993-4
Chester M, Devillers MM, Corre R, et al. Reduction in minipubertal gonadotropin levels alters reproductive lifespan and ovarian follicular loss in female mice. Hum Reprod. 2025;40(4):717-729. doi: 10.1093/humrep/deaf019
Koinuma Y, Mitsuishi Y, Winardi W, et al. Anti‐Müllerian hormone type II receptor protein expression in non‐small cell lung cancer and the effect of AMH/AMHR2 signaling on cancer cell proliferation. Thorac Cancer. 2024;15(29):2090-2099. doi: 10.1111/1759-7714.15309
Chin T, Parry RL, Donahoe PK. Human müllerian inhibiting substance inhibits tumor growth in vitro and in vivo. Cancer Res. 1991;51(8):2101-2106.
Zhang Y, Zou L, Li X, et al. SLC40A1 in iron metabolism, ferroptosis, and disease: a review. WIREs Mech Dis. 2024;16(4):1-8. doi: 10.1002/wsbm.1644
Sui X, Wang J, Zhao Z, et al. Phenolic compounds induce ferroptosis-like death by promoting hydroxyl radical generation in the Fenton reaction. Commun Biol. 2024;7(1):199. doi: 10.1038/s42003-024-05903-5
Chen L, Shen Q, Liu Y, et al. Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases. Signal Transduct Target Ther. 2025;10(1):31. doi: 10.1038/s41392-024-02071-0
Amano T, Murakami A, Murakami T, Chano T. Antioxidants and therapeutic targets in ovarian clear cell carcinoma. Antioxidants. 2021;10(2):187. doi: 10.3390/antiox10020187
He J, Liu Y, Wang X, et al. The impact of radiation dose to immune cells in stage IV non-small cell lung cancer in the era of immunotherapy. Clin Lung Cancer. 2025;26(3):221-227. doi: 10.1016/j.cllc.2025.02.006
Ding DN, Xie LZ, Shen Y, et al. Insights into the role of oxidative stress in ovarian cancer. Oxid Med Cell Longev. 2021;2021(1):8388258. doi: 10.1155/2021/8388258
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