Skip to main content
Download PDF

Laparoscopically confirmed endometriosis and the risk of incident NAFLD: a prospective cohort study

Reproductive Biology and Endocrinology volume 23, Article number: 55 (2025) Cite this article

Abstract

Background

To investigate whether endometriosis is associated with the risk of incident nonalcoholic fatty liver disease (NAFLD).

Methods

Data were retrieved from Nurses’ Health Study II with participants followed up from 1995 to 2017. A total of 61,649 participants were included in this prospective cohort study. The exposure of this study was laparoscopically confirmed endometriosis. We performed Cox proportional hazard regression analyses to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) of the association between endometriosis and NAFLD.

Results

A total of 4,774 incident NAFLD cases were recorded during a 1,313,067 person-years of follow-up. In the multivariable adjusted model, laparoscopically confirmed endometriosis was positively associated with the risk of NAFLD (HR: 1.17, 95% CI: 1.07 − 1.29). The results of the mediation analyses revealed that the association was partly attributable to hysterectomy/oophorectomy (31.6% mediated, 95% CI: 18.8−47.9%), hypercholesterolemia, hypertension and infertility. Further analysis revealed that the interaction effect of age was significant for the association between endometriosis and NAFLD (P = 0.01).

Conclusions

Laparoscopically confirmed endometriosis was positively associated with the risk of incident NAFLD. Awareness of the potential NAFLD risk should be raised for clinicians and patients during the regular follow-up of endometriosis.

Introduction

Alongside the epidemic of obesity and type 2 diabetes, the disease burden of nonalcoholic fatty liver disease (NAFLD) is increasing dramatically [1]. The global prevalence of NAFLD was estimated to be 30%, which has increased by 50% over the past two decades [2]. NAFLD is a multisystem disease associated not only with liver morbidity but also with an elevated risk of developing type 2 diabetes and cardiovascular disease [3]. The risk of coronary heart disease increased with the progression of NAFLD [4]. Overall mortality was significantly greater in subjects with NAFLD, with extrahepatic cancer-related mortality 2.16 times, hepatocellular carcinoma-related mortality 11.2 times, and cardiovascular mortality 1.35 times [5]. There is a lack of specific medication treatments for NAFLD, and an avalanche studies spotlighted on the identification of risk factors for NAFLD [6].

Endometriosis is a chronic gynecological disease that threatens nearly 10% of women of reproductive age worldwide [7]. The gold standard for diagnosis is based on the presence of histologically ectopic endometrial tissues under laparoscopy [8]. In these subjects, delayed diagnosis is common, and timely treatment is inadequate. Patients with endometriosis suffer from pelvic pain, infertility and dysmenorrhea [9]. In recent years, there has been a shift from the perspective that endometriosis is a pelvic disease to the perspective that endometriosis is a multisystem disease [7]. Accumulating evidence suggests that endometriosis is closely related to cardiovascular disease, hypertension, dyslipidemia and mood disorders [10,11,12,13,14,15]. Subjects with endometriosis are 40% more likely to develop ischemic heart disease and 19% more likely to develop cerebrovascular disease [16]. However, the association between endometriosis and cardiovascular disease reported in observational studies is limited by unmeasured confounding factors [17]. The impact of endometriosis extends far beyond the pelvis [18]. Recognizing the full effect of the disease will prompt more comprehensive therapies than are currently available.

Previous studies have reported that in mouse models, high-fat diet feeding facilitates the development of endometriosis independent of ovarian dysfunction and insulin resistance [19]. High-fat diets lead to chronic systemic inflammation and oxidative stress [20]. High-fat diets can induce NAFLD [21]. NAFLD is a multisystem disease that is closely related to cardiovascular disease and dyslipidemia and has been reported to be associated with endometriosis [10,11,12,13,14,15]. However, investigations of the associations between endometriosis and NAFLD are limited. Whether the extrapelvic effects of endometriosis include NAFLD is unknown. This study aimed to explore the relationship between laparoscopically confirmed endometriosis and NAFLD.

Methods

Study population

This study included participants from the Nurses’ Health Study II, an ongoing prospective cohort with female nurses continuously followed up since 1989. This cohort was subjected to questionnaires every two years to collect demographic information, lifestyle factors and medical history of the participants. Since the diagnostic date of NAFLD was first available in 1995, we set 1995 as the baseline for this study. Subjects were excluded if they were diagnosed with NAFLD, hepatitis B or C or excessive alcohol intake or died before baseline. The study protocol was approved by the institutional review boards of Brigham and Women’s Hospital and Harvard T. H. Chan School of Public Health.

Exposure assessment

The assessment of exposure was described in detail in previous studies [10, 11]. In the biennial questionnaires, participants were asked if they had been diagnosed with endometriosis by clinicians. If the response was yes, they further reported the year of first diagnosis and whether the diagnosis was confirmed by the gold standard, laparoscopy. In a validation study involving a subset of subjects in NHS II, a diagnosis of endometriosis was confirmed in 95 − 100% of the subjects who reported laparoscopy-confirmed endometriosis while was confirmed in only 56% of the subjects without laparoscopy confirmation [22]. Thus, we included only laparoscopy-confirmed endometriosis patients as exposures in this study to reduce possible misclassification. Information on the diagnosis of endometriosis was updated every two years, but once endometriosis was reported, they were classified into the endometriosis group for the rest of the follow-up.

Outcome assessment

The outcome of this study was physician-diagnosed NAFLD. In the questionnaires, participants reported whether they were diagnosed with fatty liver disease and reported the date of diagnosis and the presence of hepatitis B or C. The validity of the diagnosis was greater than 88% when the consistency between this criterion and the diagnostic data based on imaging or histology in medical records was compared [23]. The follow-up time was calculated from the baseline to the first occurrence of a diagnosis of incident NAFLD, death or the end of the study (June 2017), whichever came first. The outcome assessment was the same as that in previous studies that also retrieved data from the NHS II cohort [24, 25].

Covariates

The demographic data, lifestyles and medical history of the participants were reported biennially via questionnaires. In the 1989 questionnaire and subsequent biennial questionnaires, a number of features were collected, including height, smoking status, physician-diagnosed diabetes, hypercholesterolemia, hypertension and use of oral contraceptives. Race data were self-reported in 1989 and 2005. Smoking status was categorized into never, past and current. The time spent and energy expenditure of physical activity were used to estimate the metabolic equivalent task (MET), which was assessed via questionnaires in 1989, 1991, 1997, 2001, 2005, 2009 and 2013. The alternative healthy eating index 2010 (AHEI 2010) was calculated to assess diet quality. Information on reproductive factors, including age at menarche, use of oral contraceptives, infertility status, and history of hysterectomy and oophorectomy, was also collected every 2 years. Heavy drinking was defined as alcohol intake of more than 140 g per week for women. In addition, the participants were asked whether they had taken a physical exam in the past two years to evaluate the accessibility of health resources.

Statistical analyses

We conducted Cox proportional hazard regression analyses to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association between endometriosis and NAFLD risks. Proportional hazard assumption was tested, and no violation of this assumption was found. In the multivariable model, time-varying covariates were adjusted: age (months), calendar year (years), race (White, non-White), current BMI (< 18.5, 18.5 to < 22.5, 22.5 to < 25, 25 to < 30, or ≥ 30 kg/m2), smoking (never, past, current), alcohol intake (0, 0.1 − 4.9, 5 − 14.9, ≥ 15 g/day), physical activity (≤ 3, 3 − t8.9, 9 − 17.9, 18 − 26.9, ≥ 27 metabolic equivalent task-hours per week), AHEI, age at menarche (< 11, 12 − 13, ≥ 14 years old), history of infertility (yes, no), menstrual cycle irregularity (yes, no), use of oral contraceptive (never, past, current), hysterectomy/oophorectomy (yes, no), diabetes (yes, no), hypertension (yes, no), hypercholesterolemia (yes, no) and physical examination (yes, no). Mediation analyses were performed by comparing the HR and 95% CI with or without the proposed mediator, using the %Mediate macro [26]. Briefly, the macro compares the exposure effect estimate from the full model that includes the exposure, a potential intermediate variable, and any covariates to the exposure effect estimate obtained from a partial model that leaves out the potential intermediate variable.

Given the established higher risk of NAFLD in subjects who smoke [27] or who have diabetes, hypertension or dyslipidemia [28], we separately estimated the risks for NAFLD in subjects who were past or current smokers or never smokers or who had diabetes, hypertension or hypercholesterolemia. Additionally, the prevalence of NAFLD increases with age, especially after menopause [29]; therefore, we also conducted stratified analyses in those who were younger than 50 years or not. Taking into account the association between obesity and NAFLD [30], we also stratified the sample by obesity. Obesity was defined as a BMI ≥ 30 kg/m2 by the World Health Organization [31], so we used 30 kg/m2 as the cutoff point. We further investigated the interaction effect of these conditions on the association of endometriosis with NAFLD by using a log likelihood test. In sensitivity analyses, considering the delay in diagnosis between symptom onset and a definitive diagnosis of endometriosis, we returned the date of diagnosis to 2 years or even 4 years. To minimize the influence of the imbalanced distribution of covariates between groups, we conducted propensity score analyses. The covariates in the multivariable model were included in the multivariable logistic regression to estimate a propensity score, which was between 0 and 1 for each individual. All covariates were retained in the final propensity score model except for insignificant predictors. To minimize the possibility that outliers may distort the result, we excluded subjects whose propensity score was less than the 5th percentile and greater than the 95th percentile. The propensity score was then included as a covariate in the multivariable Cox proportional hazard regression model to estimate the hazard ratio (HR) and 95% confidence interval (CI). All analyses were performed with SAS 9.4 (SAS Institute Inc., Cary, NC).

Results

Population characteristics

This study included 61,649 participants, of whom 1,694 had laparoscopically confirmed endometriosis. The baseline characteristics of the subjects stratified by endometriosis diagnosis are shown in Table 1. Compared with those with no history of endometriosis, those with laparoscopically confirmed endometriosis were more likely to be White, be at an early age of menarche, be taking oral contraceptives and physical examination, and have higher proportions of hysterectomy/oophorectomy, infertility, hypercholesterolemia, hypertension and NAFLD.

Table 1 Age-standardized characteristics of the population in 1995
Full size table

Association between laparoscopically confirmed endometriosis and incident NAFLD

A total of 4,774 incident cases of NAFLD were documented during 1,313,067 person-years of follow-up (Table 2). According to the multivariable-adjusted models, laparoscopically confirmed endometriosis was positively associated with the risk of NAFLD (HR: 1.22, 95% CI: 1.10 − 1.36). This association was significantly mediated by a history of hysterectomy/oophorectomy (31.6%, 95% CI: 18.8−47.9%), hypercholesterolemia (14.2%, 95% CI: 8.0−23.9%), infertility (6.4%, 95% CI: 2.1−17.9%) and hypertension (6.3%, 95% CI: 2.7−13.8%) (Table 3).

Table 2 Hazard ratio and 95% confidence intervals of incident NAFLD according to self-reported and laparoscopically-confirmed endometriosis
Full size table
Table 3 The proportion mediated (95% CI) of the association between laparoscopically confirmed endometriosis and risk of NAFLD
Full size table

Subgroup analyses

In subgroup analyses, participants were classified according to age, BMI, smoking status, hypertension, diabetes and hypercholesterolemia (Fig. 1). Interaction analyses revealed that age had significant interactive effects on the association between laparoscopically confirmed endometriosis and incident NAFLD (P = 0.01).

Fig. 1
figure 1

Stratified analyses of the association between laparoscopically confirmed endometriosis and incident NAFLD

Full size image

Sensitivity analyses

The results of the sensitivity analyses were robust. No significant changes in the association of laparoscopically confirmed endometriosis with NAFLD were observed when accounting for a delay of two or even four years between symptom onset and the diagnosis of endometriosis (Table 4). The estimated HRs were stable in the propensity score analyses (Table 5).

Table 4 Association between endometriosis and incident NAFLD-accounting for delay between symptom onset and diagnosis
Full size table
Table 5 Association between endometriosis and incident NAFLD with adjustment for propensity score
Full size table

Discussion

Main findings

In this study, we observed a positive association between endometriosis and the risk of incident NAFLD. First, subjects with endometriosis had a higher proportion of NAFLD. Second, this association was partly attributed to a history of hysterectomy/oophorectomy, hypercholesterolemia, hypertension and infertility. Third, this association was not varied by BMI, diabetes, hypertension or hypercholesterolemia.

Interpretation

In this analysis, an increased risk of NAFLD was observed in women with endometriosis compared with those without endometriosis. The relationship between endometriosis and extrapelvic comorbidities, especially cardiovascular disease, has become a field of interest [17]. In the United Kingdom, a population-based cohort study of 56,090 subjects with endometriosis and 0.22 million controls reported that endometriosis was associated with an HR of 1.24 for cardiovascular disease [16]. A prospective study involving subjects from NHS II reported that subjects with endometriosis were at a 1.91 higher risk of angina and a 1.52 higher risk of myocardial infarction [12]. Another retrospective study of 17,543 cases and 0.07 million matched controls reported a 117% increased odds of heart failure, stroke and myocardial infarction in those with endometriosis [32]. In addition, clinical evidence suggests that endometriosis is closely related to proatherogenic dyslipidemia, with studies reporting a 1.25–1.30-fold increased risk of hypercholesterolemia [33, 34]. This study revealed for the first time that there was an independent association between endometriosis and incident NAFLD, which may provide a more comprehensive understanding of the extrapelvic effects of endometriosis. The mediation analysis indicated that this association was partially attributable to hysterectomy and oophorectomy. The mediating effects of these surgeries were also observed in studies exploring the associations between endometriosis and stroke [11] and coronary heart disease [12], which also used NHS II data. Hormone therapy and surgery are the main treatments for endometriosis [8]. Hysterectomy and oophorectomy are radical operations with a lower recurrence rate of endometriosis-related symptoms than does conservative surgery. However, there is growing concern about the sequelae of hysterectomy and oophorectomy [35]. Recent studies have shown an increased risk of cardiovascular morbidity after hysterectomy and oophorectomy, including obesity, hyperlipidemia, hypertension and coronary artery disease [36]. Early surgical menopause has been reported to be positively associated with cardiovascular disease [37]. On the basis of these results, we speculated that the treatment of endometriosis may mediate the positive relationship of endometriosis with NAFLD.

These results suggest that interdisciplinary collaboration between gynecologists and hepatologists during routine endometriosis follow-up to implement screening protocols, including hepatic ultrasound and FibroScan assessments, may be beneficial. Proactive screening and comanagement are particularly crucial for preserving long-term metabolic and reproductive health in young women navigating both conditions.

The interaction analysis revealed that age had interactive effects on the association of interest. The association between endometriosis and NAFLD was more significant in women younger than 50 years than in the control group. Endometriosis and NAFLD differ in their course at different age stages, with the former affecting mainly young women of childbearing age, with a peak incidence of 25 − 34 years [38], whereas the latter typically affects middle-aged and older individuals [17].

The underlying mechanism linking endometriosis and NAFLD remains unclear but has several possible explanations. First, chronic local and systemic proinflammatory environments in patients with endometriosis have been widely reported [39]. There is substantial evidence that endometriosis is not only a pelvic disease but also a multifactorial disease with impacts beyond the pelvis [13]. Higher levels of proinflammatory cytokines, including tumor necrosis factor-𝛼, interleukin-1 and interleukin-6, which are indicators related to the development of NAFLD, are found outside the peritoneal cavity [40]. Second, oxidative stress is increased in subjects with endometriosis [41]. The pathogenesis of NAFLD is partly due to prolonged exposure to oxidative stress. Third, surgical menopause, the surgical treatment of endometriosis, has been reported to be positively associated with the risk of developing NAFLD compared with natural menopause [42].

Strengths and limitations

This study has several limitations. First, our findings may be susceptible to detection bias, particularly in the diagnosis of incident NAFLD cases. The association between endometriosis and NAFLD in this study is highly confounding because subjects with endometriosis are likely to be evaluated with imaging for abdominal pain, which can reveal hepatic steatosis by imaging. To reduce this influence, we included physical examination in the multivariable-adjusted model and performed propensity score analyses. Second, diagnosis delay is common for endometriosis. The average time from symptom onset to diagnosis of endometriosis was seven years, whereas in the NHS II cohort, it was shorter, reported to be four years [10]. In the sensitivity analyses, we moved the date of diagnosis back to 2 years and 4 years and did not observe significant changes in the results. Third, the outcome of this study was physician-diagnosed NAFLD rather than abdominal exams such as ultrasonography for all participants, which may provide a higher and more accurate detection rate of NAFLD. The validity of physician-diagnosed NAFLD was reported to be more than 87% when it was linked to medical records, which was confirmed in an analog cohort (the NHSI cohort). The validation of NAFLD diagnosis was limited considering that it has not been validated in the NHSII cohort. The incidence rate was relatively lower than that reported in previous epidemiological studies because of the diagnostic approach used. Fourth, this was an observational study that was unable to assess the causal relationship between endometriosis and NAFLD. These results need to be further explored in future studies. Fifth, although we adjusted for numerous covariates in the multivariable regression model, certain critical factors, including genetic predisposition and hormone status, were not fully addressed due to a lack of access to serological data. Sixth, we speculated that the proinflammatory environment and oxidative stress may be partly responsible for the observed associations. This could be further confirmed by the incorporation of inflammatory markers. Unfortunately, we have no access to serological data. Seventh, the study population consisted mainly of White nurses, which may limit generalizability across genders, races and ethnicities, and additional studies in more diverse populations are needed to further confirm our results.

In conclusion, this study revealed that those with endometriosis are at increased risk of developing NAFLD. More attention needs to be paid to the extrapelvic effects of endometriosis, such as NAFLD, during the surveillance of endometriosis.

Data availability

No datasets were generated or analysed during the current study.

References

  1. Lazarus JV, Mark HE, Anstee QM, Arab JP, Batterham RL, Castera L, et al. Advancing the global public health agenda for NAFLD: a consensus statement. Nat Rev Gastroenterol Hepatol. 2022;19(1):60–78.

    Article  CAS  PubMed  Google Scholar 

  2. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen CHenry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335–47.

    Article  PubMed  Google Scholar 

  3. Anstee QM, Targher GDay CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10(6):330–44.

    Article  CAS  PubMed  Google Scholar 

  4. Mantovani A, Csermely A, Petracca G, Beatrice G, Corey KE, Simon TG, et al. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(11):903–13.

    Article  PubMed  Google Scholar 

  5. Simon TG, Roelstraete B, Khalili H, Hagström HLudvigsson JF. Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut. 2021;70(7):1375–82.

    Article  PubMed  Google Scholar 

  6. Targher G, Tilg HByrne CD. Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach. Lancet Gastroenterol Hepatol. 2021;6(7):578–88.

    Article  PubMed  Google Scholar 

  7. Zondervan KT, Becker CMMissmer SA, Endometriosis. N Engl J Med. 2020;382(13):1244–56.

    Article  CAS  PubMed  Google Scholar 

  8. Horne AWMissmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022;379:e070750.

    Article  Google Scholar 

  9. Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362(25):2389–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Farland LV, Degnan WJ, Harris HR, Tobias DKMissmer SA. A prospective study of endometriosis and risk of type 2 diabetes. Diabetologia. 2021;64(3):552–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Farland LV, Degnan WJ 3rd, Bell ML, Kasner SE, Liberman AL, Shah DK, et al. Laparoscopically confirmed endometriosis and risk of incident stroke: A prospective cohort study. Stroke. 2022;53(10):3116–22.

  12. Mu F, Rich-Edwards J, Rimm EB, Spiegelman DMissmer SA. Endometriosis and risk of coronary heart disease. Circ Cardiovasc Qual Outcomes. 2016;9(3):257–64.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kvaskoff M, Mu F, Terry KL, Harris HR, Poole EM, Farland L, et al. Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update. 2015;21(4):500–16.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Li PC, Yang YC, Wang JH, Lin SZDing DC. Endometriosis is associated with an increased risk of coronary artery disease in Asian women. J Clin Med. 2021;10(18):4173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Melo AS, Rosa-e-Silva JC, Rosa-e-Silva ACJdS, Poli-Neto OB. Ferriani RAVieira CS. Unfavorable lipid profile in women with endometriosis. Fertil Steril. 2010;93(7):2433–6.

    Article  CAS  PubMed  Google Scholar 

  16. Okoth K, Wang J, Zemedikun D, Thomas GN, Nirantharakumar KAdderley NJ. Risk of cardiovascular outcomes among women with endometriosis in the united Kingdom: a retrospective matched cohort study. BJOG. 2021;128(10):1598–609.

    Article  CAS  PubMed  Google Scholar 

  17. Marchandot B, Curtiaud A, Matsushita K, Trimaille A, Host A, Faller E, et al. Endometriosis and cardiovascular disease. Eur Heart J Open. 2022;2(1):oeac001.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Missmer SA, Commentary. Endometriosis–epidemiologic considerations for a potentially ‘high-risk’ population. Int J Epidemiol. 2009;38(4):1154–5.

    Article  PubMed  Google Scholar 

  19. Heard ME, Melnyk SB, Simmen FA, Yang Y, Pabona JMSimmen RC. High-Fat diet promotion of endometriosis in an immunocompetent mouse model is associated with altered peripheral and ectopic lesion redox and inflammatory status. Endocrinology. 2016;157(7):2870–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chae SJ, Kim H, Jee BC, Suh CS, Kim SHKim JG. Tumor necrosis factor (TNF)-TNF receptor gene polymorphisms and their serum levels in Korean women with endometriosis. Am J Reprod Immunol. 2008;60(5):432–9.

    Article  CAS  PubMed  Google Scholar 

  21. Lian C-Y, Zhai Z-Z, Li Z-FW. High fat diet-triggered non-alcoholic fatty liver disease: A review of proposed mechanisms. Chem Biol Interact. 2020;330:109199.

    Article  CAS  PubMed  Google Scholar 

  22. Shafrir AL, Wise LA, Palmer JR, Shuaib ZO, Katuska LM, Vinayak P, et al. Validity of self-reported endometriosis: a comparison across four cohorts. Hum Reprod. 2021;36(5):1268–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American association for the study of liver diseases. Hepatology. 2018;67(1):328–57.

    Article  PubMed  Google Scholar 

  24. Kim MN, Lo C-H, Corey KE, Liu P-H, Ma W, Zhang X, et al. Weight gain during early adulthood, trajectory of body shape and the risk of nonalcoholic fatty liver disease: A prospective cohort study among women. Metabolism. 2020;113:154398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kim MN, Lo C-H, Corey KE, Luo X, Long L, Zhang X, et al. Red meat consumption, obesity, and the risk of nonalcoholic fatty liver disease among women: evidence from mediation analysis. Clin Nutr. 2022;41(2):356–64.

    Article  CAS  PubMed  Google Scholar 

  26. Banay RF, James P, Hart JE, Kubzansky LD, Spiegelman D, Okereke OI, et al. Greenness and depression incidence among older women. Environ Health Perspect. 2019;127(2):27001.

    Article  PubMed  Google Scholar 

  27. Yuan S, Chen J, Li X, Fan R, Arsenault B, Gill D, et al. Lifestyle and metabolic factors for nonalcoholic fatty liver disease: Mendelian randomization study. Eur J Epidemiol. 2022;37(7):723–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Byrne CDTargher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1 Suppl):S47–64.

    Article  Google Scholar 

  29. Perumpail BJ, Khan MA, Yoo ER, Cholankeril G, Kim DAhmed A. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol. 2017;23(47):8263–76.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Polyzos SA, Kountouras JMantzoros CS. Obesity and nonalcoholic fatty liver disease: from pathophysiology to therapeutics. Metabolism. 2019;92:82–97.

    Article  CAS  PubMed  Google Scholar 

  31. Elmaleh-Sachs A, Schwartz JL, Bramante CT, Nicklas JM. Gudzune KAJay M. Obesity management in adults: A review. JAMA. 2023;330(20):2000–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chiang HJ, Lan KC, Yang YH, Chiang JY, Kung FT, Huang FJ, et al. Risk of major adverse cardiovascular and cerebrovascular events in Taiwanese women with endometriosis. J Formos Med Assoc. 2021;120(1 Pt 2):327–36.

    Article  PubMed  Google Scholar 

  33. Mu F, Rich-Edwards J, Rimm EB, Spiegelman D. Forman JPMissmer SA. Association between endometriosis and hypercholesterolemia or hypertension. Hypertension. 2017;70(1):59–65.

    Article  CAS  PubMed  Google Scholar 

  34. Nagai K, Hayashi K, Yasui T, Katanoda K, Iso H, Kiyohara Y, et al. Disease history and risk of comorbidity in women’s life course: a comprehensive analysis of the Japan nurses’ health study baseline survey. BMJ Open. 2015;5(3):e006360.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Stewart EA, Missmer SARocca WA. Moving Beyond Reflexive and Prophylactic Gynecologic Surgery. Mayo Clin Proc. 2021;96(2):291–294.

  36. Hassan H, Allen I, Sofianopoulou E, Walburga Y, Turnbull C, Eccles DM, et al. Long-term outcomes of hysterectomy with bilateral salpingo-oophorectomy: a systematic review and meta-analysis. Am J Obstet Gynecol. 2024;230(1):44–57.

    Article  PubMed  Google Scholar 

  37. Honigberg MC, Zekavat SM, Aragam K, Finneran P, Klarin D, Bhatt DL, et al. Association of premature natural and surgical menopause with incident cardiovascular disease. JAMA. 2019;322(24):2411–21.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Shafrir AL, Farland LV, Shah DK, Harris HR, Kvaskoff M, Zondervan K, et al. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018;51:1–5.

    Article  CAS  PubMed  Google Scholar 

  39. Furuya M, Tanaka R, Miyagi E, Kami D, Nagahama K, Miyagi Y, et al. Impaired CXCL4 expression in tumor-associated macrophages (TAMs) of ovarian cancers arising in endometriosis. Cancer Biol Ther. 2012;13(8):671–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lin Y-J, Lai M-D, Lei H-YW. Neutrophils and macrophages promote angiogenesis in the early stage of endometriosis in a mouse model. Endocrinology. 2006;147(3):1278–86.

    Article  CAS  PubMed  Google Scholar 

  41. Gupta S, Agarwal A, Krajcir NAlvarez JG. Role of oxidative stress in endometriosis. Reprod Biomed Online. 2006;13(1):126–34.

    Article  CAS  PubMed  Google Scholar 

  42. Wang J, Wu AH, Stanczyk FZ, Porcel J, Noureddin M, Terrault NA, et al. Associations between reproductive and Hormone-Related factors and risk of nonalcoholic fatty liver disease in a multiethnic population. Clin Gastroenterol Hepatol. 2021;19(6):1258–66.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all participants and staff of the Nurses’ Health Study II for their great contributions to this research.

Funding

US National Institutes of Health: U01 CA176726. HD57210, HD96033, and HD99623.

Author information

Author notes

  1. Hangkai Huang and Zhening Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Zhejiang Provincial Clinical Research Centre for Digestive Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China

    Hangkai Huang, Zhening Liu, Jiaqi Ruan & Chengfu Xu

  2. Sanmenwan Branch, The First Affiliated Hospital, Zhejiang University School of Medicine, Taizhou, China

    Zejun Fang

Authors
  1. Hangkai Huang
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Zhening Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Jiaqi Ruan
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Zejun Fang
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Chengfu Xu
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Concept and design: Hangkai Huang. Acquisition, analysis, or interpretation of data: Hangkai Huang, Zhening Liu, Jiaqi Ruan and Zejun Fang. Statistical analysis: Hangkai Huang. Drafting of the manuscript: Hangkai Huang. Critical revision of the manuscript for important intellectual content: Chengfu Xu. Supervision: Chengfu Xu.

Corresponding author

Correspondence to Chengfu Xu.

Ethics declarations

Ethics approval and consent to participate

The study protocol was approved by the institutional review boards of Brigham and Women’s Hospital and Harvard T. H. Chan School of Public Health. All the experiments were performed in accordance with the Declaration of Helsinki.

Consent to participate

Return of the completed questionnaire was considered to imply consent.

Consent for publication

Not applicable.

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.

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/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, H., Liu, Z., Ruan, J. et al. Laparoscopically confirmed endometriosis and the risk of incident NAFLD: a prospective cohort study. Reprod Biol Endocrinol 23, 55 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12958-025-01391-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12958-025-01391-2

Keywords

Reproductive Biology and Endocrinology

ISSN: 1477-7827

Contact us