Abstract
This study aimed to investigate the impact of dyslipidemia on outcomes of fertility-preserving treatment in patients with endometrioid endometrial cancer (EEC) or endometrial atypical hyperplasia (EAH). A total of 406 patients, including 118 EEC and 288 EAH, who received fertility-sparing treatment between January 2017 and December 2020 were included and divided into a dyslipidemia group (n = 282) and a non-dyslipidemia group (n = 124). The 16-/32-week complete response (CR) rate, pregnancy outcome, and recurrence were compared between patients with and without dyslipidemia. Furthermore, we explored the effect of different indicators of dyslipidemia, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), on the therapeutic effects of fertility-preserving treatment. A total of 282 (69.5%) patients were diagnosed with dyslipidemia, and 38 patients were diagnosed with mixed dyslipidemia. The 16-/32-week CR rate, pregnant rate, live birth rate, and recurrence did not have significant differences between patients with and without dyslipidemia. Patients with mixed dyslipidemia had a lower 32-week CR rate (42.1% vs.65.5%, P = 0.004) and a longer treatment duration to achieve CR (33.4 weeks vs. 27.0 weeks, P = 0.039, HR: 0.73, 95%CI: 0.53–0.98) than those without mixed dyslipidemia. Multivariate logistic regression analyses demonstrated that mixed dyslipidemia was significantly associated with a lower 32-week CR rate (OR: 0.322, 95% CI: 0.134–0.775, P = 0.011). Patients with both overweight and mixed dyslipidemia had the lowest 32-week CR rate (12/31, 38.5%, P = 0.007) and longest median treatment duration to CR (34.0 weeks, 95%CI: 25.7–42.3 weeks, P = 0.025). Mixed dyslipidemia was an independent risk factor for fertility-preserving treatment outcomes in EAH or EEC patients, as this group had a lower 32-week CR rate and a longer treatment duration to achieve CR than those without mixed dyslipidemia.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Rakha, E. et al. Clinical outcome of atypical endometrial hyperplasia diagnosed on an endometrial biopsy: institutional experience and review of literature. Am. J. Surg. Pathol. 36 (11), 1683–1690 (2012).
Vitale, S. G. et al. Hysteroscopy in the management of endometrial hyperplasia and cancer in reproductive aged women: new developments and current perspectives. Transl Cancer Res. 9 (12), 7767–7777 (2020).
Liu, S. et al. Effects of Weight Status and Related Metabolic Disorders on Fertility-Sparing Treatment Outcomes in Endometrial Atypical Hyperplasia and Endometrial Cancer: A Retrospective Study. Cancers (Basel), 14(20). (2022).
Ciccone, M. A. et al. Effectiveness of progestin-based therapy for morbidly obese women with complex atypical hyperplasia. Arch. Gynecol. Obstet. 299 (3), 801–808 (2019).
Yang, B. et al. Insulin resistance and overweight prolonged fertility-sparing treatment duration in endometrial atypical hyperplasia patients. J. Gynecol. Oncol. 29 (3), e35 (2018).
Yang, X. et al. Effects of Metabolic Syndrome and Its Components on the Prognosis of Endometrial Cancer. Front. Endocrinol. (Lausanne). 12, 780769 (2021).
Lavie, O. et al. The effect of statins on risk and survival of gynecological malignancies. Gynecol. Oncol. 130 (3), 615–619 (2013).
Koh, W. J. et al. Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Canc Netw. 16 (2), 170–199 (2018).
Smith, K. B. & Smith, M. S. Obesity Stat. Prim. Care, 43(1), 121 – 35. (2016).
Zhonghua, X., Guan, X., Zhi B. Z. Chinese guideline for the management of dyslipidemia in adults. 44 (10), 833–853. (2016).
Paquette, M. et al. Prevalence of Dysbetalipoproteinemia in the UK Biobank According to Different Diagnostic Criteria. J. Clin. Endocrinol. Metab. (2024).
Matthews, D. R. et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28 (7), 412–419 (1985).
Shan, W. et al. Hyperinsulinemia is associated with endometrial hyperplasia and disordered proliferative endometrium: a prospective cross-sectional study. Gynecol. Oncol. 132 (3), 606–610 (2014).
Trabert, B. et al. Metabolic syndrome and risk of endometrial cancer in the united states: a study in the SEER-medicare linked database. Cancer Epidemiol. Biomarkers Prev. 24 (1), 261–267 (2015).
Hanson, R. L. et al. Components of the metabolic syndrome and incidence of type 2 diabetes. Diabetes 51 (10), 3120–3127 (2002).
Klein, B. E., Klein, R. & Lee, K. E. Components of the metabolic syndrome and risk of cardiovascular disease and diabetes in Beaver Dam. Diabetes Care. 25 (10), 1790–1794 (2002).
Li, X. et al. Insulin Resistance and Metabolic Syndrome Increase the Risk of Relapse For Fertility Preserving Treatment in Atypical Endometrial Hyperplasia and Early Endometrial Cancer Patients. Front. Oncol. 11, 744689 (2021).
Ding, Y. et al. Metabolic syndrome is an independent risk factor for time to complete remission of fertility-sparing treatment in atypical endometrial hyperplasia and early endometrial carcinoma patients. Reprod. Biol. Endocrinol. 20 (1), 134 (2022).
Hefetz-Sela, S. & Scherer, P. E. Adipocytes: impact on tumor growth and potential sites for therapeutic intervention. Pharmacol. Ther. 138 (2), 197–210 (2013).
Dossus, L. et al. Tumor necrosis factor (TNF)-alpha, soluble TNF receptors and endometrial cancer risk: the EPIC study. Int. J. Cancer. 129 (8), 2032–2037 (2011).
Simo, R. et al. Novel insights in SHBG regulation and clinical implications. Trends Endocrinol. Metab. 26 (7), 376–383 (2015).
Lv, Q. Y. et al. Increased TET1 Expression in Inflammatory Microenvironment of Hyperinsulinemia Enhances the Response of Endometrial Cancer to Estrogen by Epigenetic Modulation of GPER. J. Cancer. 8 (5), 894–902 (2017).
Patel, B. G. et al. Progesterone resistance in endometriosis: origins, consequences and interventions. Acta Obstet. Gynecol. Scand. 96 (6), 623–632 (2017).
Vitale, S. G. et al. Risk of endometrial malignancy in women treated for breast cancer: the BLUSH prediction model - evidence from a comprehensive multicentric retrospective cohort study. Climacteric 27 (5), 482–488 (2024).
Barr, C. E. et al. Weight Loss During Intrauterine Progestin Treatment for Obesity-associated Atypical Hyperplasia and Early-Stage Cancer of The Endometrium. Cancer Prev. Res. (Phila). 14 (11), 1041–1050 (2021).
Kuribayashi, Y. et al. Frequency of endometrial cancer and atypical hyperplasia in infertile women undergoing hysteroscopic polypectomy. J. Obstet. Gynaecol. Res. 43 (9), 1465–1471 (2017).
Acknowledgements
We thank all the patients who participated in this study.
Funding
This work was funded by the National Key R&D Program of China (Grant No. 2022YFC2704301 and 2022YFC2704305), Medical Engineering Joint Fund of Fudan University (Grant No. yg2023-08), and Shanghai Anticancer Association EYAS PROJECT (Grant No. SACA-CY22C08), and The Shanghai Municipal Health Commission Youth Program (Grant No. 20224Y0084).
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. Data collection was performed by Shuhan Luo, Manrong Wang, Qujia Gama and Lulu Wang. Data analysis was performed by Shuhan Luo, Pengfei Wu and Sijia Liu. The first draft of the manuscript was written by Shuhan Luo and Pengfei Wu. The manuscript was edited by Xuezhen Luo and Pengfei Wu.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethical approval
The retrospective study was approved by the Ethics Committee of the Obstetrics and Gynecology Hospital of Fudan University (No. 2022 − 203).
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Luo, S., Wang, M., Shan, W. et al. Effects of dyslipidemia on fertility-sparing treatment outcomes in endometrial atypical hyperplasia and endometrial cancer: a large cohort study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-46711-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-026-46711-7
