Endometriosis, subclinical cardiac remodeling, and cardiovascular risk: mechanistic insights from cardiac magnetic resonance and mediation analysis

Background Endometriosis is a systemic gynecological disorder affecting ~ 10% of reproductive-aged women and shares pathophysiological features with cardiovascular disease (CVD). However, its associations with cardiac remodeling and CVD risk, as well as underlying mechanisms, remain unclear.

This study utilized data from the UK Biobank, comprising 6,158 women diagnosed with endometriosis and 229,453 women without the condition. To validate our results, we employed a hospital cohort from the Second Affiliated Hospital of the University of South China, which included 612 women with laparoscopically confirmed endometriosis and 612 age-matched controls. We applied multivariable-adjusted Cox proportional hazards models to investigate the association between endometriosis and the risk of CVD. Additionally, generalized linear models were used to evaluate cardiac magnetic resonance (CMR) metrics. Mediation analyses were conducted to quantify the contributions of 32 biomarkers, with a particular emphasis on metabolic indices (e.g., triglyceride-glucose (TyG)-related indices, lipid accumulation product (LAP)), inflammatory markers (C-reactive protein (CRP), inflammation score (INFLA)), oxidative stress indicators (urate, bilirubin), and hormonal status markers (sex hormone-binding globulin (SHBG)).

Over a median 13-year follow-up, 23,239 CVD events occurred. Endometriosis was associated with increased risks of CVD (HR 1.18, 95% CI 1.09–1.29) and coronary heart disease (CHD) (HR 1.25, 95% CI 1.12–1.40). These findings were robust across multiple sensitivity analyses and consistently replicated in the external Chinese cohort, with an additional significant association observed for stroke (HR: 1.19, 95% CI: 1.03–1.40). CMR imaging revealed subclinical concentric remodeling, including increased interventricular septal thickness (1.11%, 95% CI 0.13–2.11), relative wall mass (1.11%, 95% CI 0.05–2.17), and septal-to-lateral wall thickness ratio (0.64%, 95% CI 0.00–1.29). Mediation analyses identified metabolic dysfunction as the primary pathway, with TyG-related indices (15.4%–17.3%), LAP (11.8%), and triglycerides (8.9%) accounting for the largest proportions, followed by inflammation (CRP: 11.1%; INFLA: 3.7%) and oxidative stress (urate: 6.0%).

Endometriosis is associated with increased CVD risk and early subclinical cardiac remodeling, largely mediated by metabolic and inflammatory pathways. These findings underscore the necessity of cardiovascular risk stratification and metabolic monitoring in the clinical management of women with endometriosis. Highlights 1. Women with endometriosis face higher risks of cardiovascular disease, especially coronary heart disease. 2. CMR reveals subtle but significant adverse cardiac remodeling in women with endometriosis. 3. Metabolic dysfunction and systemic inflammation, notably TyG-related indices and LAP, predominantly mediate the link between endometriosis and cardiovascular risk. Similar content being viewed by others

We thank the UK Biobank (Application Number: 529233) and its participants, as well as the patients, clinicians, and staff at the Second Affiliated Hospital of University of South China for their important contributions to this study. Clinical trial number Not appliable. Funding This research was funded by the National Key Research and Development Program of China, grant number 2022YFC2704100 and the National Natural Science Foundation of China, grant number 82371648. Author information Authors and Affiliations Corresponding authors Ethics declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki. The UK Biobank received ethical approval from the North West Multi-centre Research Ethics Committee on 22 August 2006 (06/MRE08/65), with subsequent renewals every five years. For the external validation cohort, the study protocol was approved by the Institutional Review Board of the Second Affiliated Hospital of the University of South China (No. 2025006). Written informed consent was obtained from all participants prior to their inclusion in the study. Consent for publication Not appliable. Competing interests The authors declare no competing interests. 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 Feng, Y., Nie, K., Xiao, M. et al. Endometriosis, subclinical cardiac remodeling, and cardiovascular risk: mechanistic insights from cardiac magnetic resonance and mediation analysis. Reprod Biol Endocrinol (2026). https://doi.org/10.1186/s12958-026-01564-7 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12958-026-01564-7