META-ANALYSIS OF THE CAUSAL RELATIONSHIP BETWEEN ENDOMETRIOSIS AND THE DEVELOPMENT OF VENOUS THROMBOEMBOLISM
DOI:
https://doi.org/10.32782/2411-9164.23.2-5Keywords:
hemostasis, endometriosis, gynecology, venous thrombosis, therapy of endometriosis, venous thrombosis correlation, hemocoagulationAbstract
Objective. To investigate the impact of endometriosis on the occurrence of venous thromboembolism (VTE) in oral contraceptive (OC) users. A pooled analysis was performed using a harmonized dataset from international patient-centered cohort studies: INAS-VIPOS, INAS-SCORE and INAS-FOCUS. The studies were conducted in eleven European countries, the USA and Canada. Participants were individuals newly prescribed with or without OC, with a history of endometriosis but no recorded VTE. Methods. Detailed data were collected using self-administered questionnaires at baseline and every 6–12 months thereafter. All self-reported VTEs were verified by healthcare professionals and assessed by an independent adjudicating committee. Incidence rates (IRs) were calculated per 10,000 women per year. Time-to-event analysis was used to determine the association between endometriosis and VTE with crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) calculated using the stabilized inverse probability of treatment weighting (IPTW). Results. A total of 22,072 women had a diagnosis of endometriosis, while 91,056 women did not. Women with endometriosis accounted for 78,751 women per year, among whom 41 VTE events were reported (HR: 5.2/10,000, 95% CI: 3.7–7.1). In comparison, 127 VTEs were reported among 310,501 women per year in women without endometriosis (HR: 4.1/10,000, 95% CI: 3.4–4.9). The adjusted HR for VTE in women with endometriosis was 1.79 (95% CI: 1.24–2.57) using a stabilized IPTW controlling for age, body mass index, smoking, education, age at menarche, and family history of VTE. Subgroup and sensitivity analyses yielded similar results. Conclusion. These findings highlight the importance of considering endometriosis as a potential contributing factor to VTE in women using OCs. However, further studies are needed to understand the association between endometriosis and VTE.
References
De Corte, P., Milhoranca, I., Mechsner, S., Oberg, A. S., Kurth, T., & Heinemann, K. (2025). Unravelling the Causal Relationship between Endometriosis and the Risk for Developing Venous Thromboembolism: A Pooled Analysis. Thrombosis and Haemostasis, 125(04), 385–394. https://doi.org/10.1055/a-2407-9498
Giudice, L. C. (2010). Clinical practice. Endometriosis. N Engl J Med. 362(25), 2389–2398
Fan, Y-H., Leong, P-Y., Chiou, J-Y., Wang, Y-H., Ku M-H, Wei JC-C. (2021). Association between endometriosis and risk of systemic lupus erythematosus. Sci Rep. 11(01), 532.
Surrey, E. S., Soliman, A. M., Johnson, S. J., Davis, M., Castelli-Haley, J., Snabes, M. C. (2018). Risk of developing comorbidities among women with endometriosis: a retrospective matched cohort study. J Womens Health (Larchmt) 27(09), 1114–1123.
Teng, S-W., Horng, H-C, Ho., C-H, Yen., M-S., Chao, H-T., Wang P-H. (2016); Taiwan Association of Gynecology Systematic Review Group.Women with endometriosishavehigher comorbidities:Analysis ofdomesticdata in Taiwan. J Chin Med Assoc. 79(11), 577–582.
Mu, F., Rich-Edwards, J., Rimm, E. B., Spiegelman, D., Missmer, S. A. (2016). Endometriosis and risk of coronary heart disease. Circ Cardiovasc Qual Outcomes 9(03), 257–264.
Farland, L. V., Degnan, W. J. III, Bell, M. L., et al. (2022). Laparoscopically confirmed endometriosis and risk of incident stroke: a prospective cohort study. Stroke 53(10), 3116–3122.
Mu, F., Rich-Edwards, J., Rimm, E. B., Spiegelman, D., Forman, J. P. (2017). Missmer SA. Association between endometriosis and hypercholesterolemia or hypertension. Hypertension. 70(01), 59–65.
Heinemann, K., Imthurn, B., Marions, L., et al. (2020). Safety of Dienogest and other hormonal treatments for endometriosis in real-world clinical practice (VIPOS): a large noninterventional study. Adv Ther. 37(05), 2528–2537.
Becker, K, Heinemann, K, Imthurn, B, et al. (2021). Real world data on symptomology and diagnostic approaches of 27,840 women living with endometriosis. Sci Rep. 11(01), 20404.
Dinger, JC RS. INternational Active Surveillance Study – Folate and Oral ContraceptivesUtilization Study (INAS-FOCUS); INAS-FOCUS Study: 12th update report. Retrieved from: https://catalogues.ema.europa.eu/sites/default/files/document_files/IFOC_FinalStudyReport_Public%20Version%2020200819.pdf
Jürgen, D., Klaas, H., Sabine, M. (2020). Combined oral contraceptives containing dienogest and estradiol valerate may carry a lower risk of venous and arterial thromboembolism compared to conventional preparations: Results from the extended INAS-SCORE study. Front in Womens Health. 05(01), 1–8.
Heinemann, K., Reed, S., Moehner, S., Minh, T. D. (2015). Comparative contraceptive effectiveness of levonorgestrel-releasing and copper intrauterine devices: the European Active Surveillance Study for Intrauterine Devices. Contraception. 91(04), 280–283.
Heinemann, K., Reed, S., Moehner, S., Minh, T. D. (2015). Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception. 91(04), 274–279.
Austin, P. C. (2011). An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res. 46(03), 399–424.
Austin, P. C. (2014). The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 33(07),1242–125.8
Hernán, M. A., Robins, J. M. (2021). Casual Inference:What If. Boca Raton, FL:CRC Press.
Rosenbaum, P. R., Rubin, D. B. (1983). The central role of the propensity score in observational studies for causal effects. Biometrika. 70 (01), 41–55.
Robins, J. M., Hernán, M. A., Brumback, B. (2000). Marginal structural models and causal inference in epidemiology. Epidemiology. 11 (05), 550–560.
Rosenbaum, PRRD. (1984). Reducing bias in observational studies using subclassification on the propensity score. Journal of the American Statistical Association. J Am Stat Assoc. 79, 516–524.
Greenland, S., Pearl, J., Robins, J. M. (1999). Causal diagrams for epidemiologic research. Epidemiology. 10(01), 37–48.
Wiegers, HMG., Scheres, LJJ., Tahir, L., Hutten, B. A., Middeldorp, S., & Mijatovic, V. (2022). Risk of venous thromboembolism in women with endometriosis. Thrombosis Research, 217, 104–106. https://doi.org/10.1016/j.thromres.2022.07.014
