{"paper_id":"33f3cc9b-dce7-4139-9051-857079fdde2d","body_text":" Corresponding author: Ifeoma Nwamaka Monago \nCopyright © 2026 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. \nEndometriosis as an underrecognized risk factor for heart failure: Mechanistic \ninsights from inflammation, estrogen dysregulation, and cardiometabolic overlap \nIfeoma Nwamaka Monago 1, * , Chibuike Stephen Nzereogu 2, Favour Kosisochukwu Mbakwe 3, Elijah \nOluwatosin Olopade 4, Chukwuemeka Kandudi Monago 5, Marcus Chukwunonso Mbakwe 6, Samuel Ibekwe \nObasi 7  and Anthonia Oluyemi Agboola 8\n1 Department of Community Medicine and Primary Health Care, Faculty of Medicine, College of Health Sciences, Nnamdi \nAzikiwe University, Awka, Nigeria. \n2 Department of Pharmacognosy and Phytotherapy, University of Port-harcourt, Port-harcourt, Nigeria. \n3 Department of Medicine, Obafemi Awolowo University, Ile Ife, Nigeria. \n4 Department of Biochemistry, Adeleke University, Ede, Nigeria. \n5 Department of Medicine and Surgery, Igbinedion University, Okada, Nigeria. \n6 Department of Obstetric and Gynaecology, Usmanu Danfodiyo University, Sokoto, Nigeria. \n7 Department of Public Health, Anglia Ruskin University, Cambridge, UK. \n8 Department of Biochemistry, Wesley University, Ondo, Nigeria. \nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \nPublication history: Received on 24 February 2026; revised on 16 April 2026; accepted on 18 April 2026 \nArticle DOI: https://doi.org/10.53771/ijbpsa.2026.11.2.0036 \nAbstract \nEndometriosis is often treated as a localised gynaecological issue, but a growing body of evidence shows it has broader \nsystemic effects including an increase in the risk of heart failure. The condition affects roughly 10% of women of \nreproductive age and is linked through large cohort studies and meta -analyses to elevated rates of ischaemic heart \ndisease (IHD), stroke and arrhythmias (adjusted hazard ratios typically 1.1 to 1.5), with heart failure emerging as a \nsignal in several nationwide registries. The connection appears to arise from three overlapping mechanisms; Persistent \nlow-grade inflammation releases pro -inflammatory cytokines (notably IL -6, TNF -α, and IL -1β) into the circulation \nwhich promotes endothelial dysfunction and oxidative stress, Oestrogen dysregulation which plays a paradoxical role: \nlocally, excessive production in endometriotic lesions sustains inflammation while systemic hormonal imbalance can \nundermine vascular protection and contribute to pro -thrombotic or arrhythmogenic effects. Co ncurrent \ncardiometabolic disturbances such as insulin resistance, atherogenic dyslipidaemia, central adiposity and elevated \ncardiometabolic index further strain the myocardium and predisposes one  to diastolic dysfunction particularly in the \nheart failure with preserved ejection fraction phenotype that disproportionately affects women. Clinically, this means \nendometriosis should no longer be managed in isolation. Routine cardiovascular risk assessment such as blood \npressure, lipid profile, glucose tolerance and possibly selected inflammatory markers should become standard in follow-\nup especially for younger patients or those with long disease duration or have had prior surgery. Closer collaboration \nbetween gynaecologists and cardiologists together with prospective studies that track true heart failure incidence and \nevaluate targeted interventions (anti -inflammatory strategies, optimised hormonal regimens, lifestyle modification) \ncould substantially reduce preventable cardiac morbidity in this population. \nKeywords: Endometriosis; Heart Failure; Inflammation; Estrogens; Risk Factors; Cardiovascular Diseases; Insulin \nResistance; Metabolic Syndrome \n\n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n10 \n1. Introduction \n1.1. Overview  \nEndometriosis is a chronic, estrogen-dependent gynecological disorder characterized by the presence of endometrial -\nlike tissue outside the uterus, leading to debilitating symptoms such as pelvic pain, dysmenorrhea, dyspareunia and \ninfertility. It affects millions of women worldwide and imposes a significant burden on quality of life. Healthcare systems \nalso play a part due to diagnostic delays and limited curative options. Emerging evidence suggests systemic implications \nbeyond reproductive health, including potential links to cardiovascular disease (CVD) through mechanisms like chronic \ninflammation and hormonal dysregulation. This review focuses on endometriosis as an underrecognized risk factor for \nheart failure (HF). In this study, epidemiological data an d mechanistic insights from inflammation, estrogen \ndysregulation, and cardiometabolic overlap are synthesized in order to advocate for greater awareness and targeted \ncardiovascular screening in affected women. \n1.2. Epidemiology and Burden of Endometriosis  \nEndometriosis predominantly affects women of reproductive age with global prevalence estimates varying based on \ndiagnostic methods and population studied [1]. In general population or health system data, prevalence ranges from \napproximately 1 to 10% while higher rates (up to 30 to 50%) are reported in women with infertility or chronic pelvic \npain [2,3]. For instance, population -based studies indicate a prevalence of around 6 to 10% among women of \nreproductive age though administrative or insurance data ofte n report lower figures (around 1 to 2%) due to \nunderdiagnosis [1,4]. Diagnostic challenges, including reliance on laparoscopy for confirmation and average delays of 7 \n-to 10 years from symptom onset contribute to this variability and underestimate the true burden [1,5]. \nThe chronic nature of endometriosis manifests as recurrent pelvic pain, infertility in around 30% to 50% of cases and \nreduced quality of life, often requiring long -term management with hormonal therapies, surgery or pain control [1,3]. \nThese factors impose substantial economic and psychosocial costs, with affected women experiencing higher rates of \nabsenteeism, healthcare utilization as well as comorbid conditions [3]. Early menarche, short menstrual cycles and \nnulliparity are established risk factors while parity and higher body mass index appear protective in some cohorts [1]. \nDespite advances in awareness, endometriosis remains underrecognized as a systemic disease, with limited \nlongitudinal data on long -term extrapelvic effects. This gap highlights the need to explore its associations with other \nchronic conditions including cardiovascular implications. \n1.3. Overview of Cardiovascular Disease in Women and Heart Failure Epidemiology  \nCardiovascular disease remains the leading cause of mortality in women globally, yet sex -specific differences in \npresentation, risk factors, and outcomes are often underappreciated [6]. Women tend to develop CVD later than men \nbut experience higher morbidi ty from conditions like heart failure with preserved ejection fraction (HFpEF), which \npredominates in postmenopausal women and is linked to inflammation and metabolic factors [7,8]. Traditional risk \nfactors (hypertension, diabetes, dyslipidemia) interact w ith female -specific elements such as hormonal transitions, \npregnancy complications, and autoimmune/inflammatory conditions [6]. \nHeart failure affects millions worldwide, with increasing incidence in women due to aging populations and rising \ncardiometabolic comorbidities. HFpEF in particular shows a female predominance (women comprise approximately \n55% of HFpEF cases) and is associa ted with chronic low -grade inflammation, endothelial dysfunction and estrogen \nfluctuations pathways that overlap with endometriosis [7,8]. Sex hormones play a protective role in premenopausal \nwomen, but dysregulation can contribute to vascular stiffness and cardiac remodeling [7]. \nThe underrecognition of non-traditional risk factors in women, including chronic inflammatory gynecological disorders \nmay delay prevention strategies. Emerging data suggest that conditions like endometriosis could amplify CVD \nsusceptibility through shared mechanisms. \n1.4. Rationale for Linking Endometriosis to Cardiovascular Disease and Heart Failure  \nEndometriosis involves systemic chronic inflammation, oxidative stress and estrogen/progesterone imbalances, which \nparallel pathways in CVD pathogenesis, including endothelial dysfunction and atherosclerosis [9]. Large cohort studies \nhave demonstrated modest but significant associations between endometriosis and increased risks of ischemic heart \ndisease, stroke, arrhythmias and composite CVD events, with adjusted hazard ratios typically in the 1.1 to 1.5 range \n[10,11]. While HF -specific links are emerging a nd sometimes modest or inconsistent across meta -analyses, recent \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n11 \nnationwide data indicate a small elevated risk (adjusted HR ~1.11 for HF) especially in long-term follow-up [12]. These \nassociations may be amplified by confounders like early hysterectomy/oophorectomy in endometriosis patients which \naccelerates estrogen decline and CVD risk. The underrecognition of endometriosis as a CVD/HF contributor stems from \nits primary gynecological framing, despite mechanistic relationship with inflammatory and hormonal drivers of cardiac \nremodeling [9]. \nThis review synthesizes these connections, emphasizing mechanistic insights to position endometriosis as an \nunderrecognized HF risk factor warranting multidisciplinary attention. \n2. Epidemiological Evidence Linking Endometriosis to Heart Failure and Cardiovascular Outcomes \n2.1. Overview  \nThe epidemiological landscape of endometriosis in relation to cardiovascular outcomes has expanded substantially in \nrecent years, driven by large cohort studies and meta -analyses of population -based data. While initial observations \nfocused on broader cardiovascular disease (CVD) associations, attention has increasingly turned to specific endpoints, \nincluding heart failure (HF), ischemic heart disease (IHD), stroke, arrhythmias, and composite major adverse \ncardiovascular events (MACE). This section reviews k ey evidence from cohort studies and systematic reviews/meta -\nanalyses, highlighting modest but consistent risk elevations for several CVD outcomes, with particular emphasis on HF \nassociations that remain modest and sometimes heterogeneous. Subgroup consider ations, such as surgical history \n(hysterectomy/oophorectomy), are also addressed to contextualize potential confounders. \n2.2. Key Cohort Studies and Nationwide Registries  \nLarge population -based cohorts have provided robust evidence for an association between endometriosis and \nincreased CVD risk. In a nationwide Danish registry study involving over 60,000 women with endometriosis matched \nto controls, the adjusted hazard rati o (HR) for the composite endpoint of acute myocardial infarction and ischemic \nstroke was 1.15 (95% CI 1.11 to 1.20) over long -term follow -up (median 16 years) [13]. This study also reported \nelevated risks for arrhythmias (adjusted HR 1.21; 95% CI 1.17 to 1.25) and heart failure (adjusted HR 1.11; 95% CI 1.05 \nto 1.18), though absolute risk differences remained small [13]. \nSimilar patterns emerge from other registries. A Canadian population -based analysis of over 166,000 women with \nendometriosis found an increased risk of hospital admission for CVD (adjusted HR 1.14; 95% CI 1.10 to 1.19), including \nsecondary CVD events (adjusted HR 1.26; 95% CI 1.23 to 1.30), with specific elevations in congestive heart failure among \nsecondary outcomes [14]. Earlier prospective cohorts such as the Nurses' Health Study II, demonstrated higher relative \nrisks for myocardial infarction (RR 1.52; 95% CI 1.17 to 1.98) and composite coronary heart disease endpoints (RR 1.62; \n95% CI 1.39 to 1.89) in laparoscopically confirmed cases, independent of traditional confounders [15]. These findings \nunderscore a consistent, albeit modest, signal across diverse populations. \n2.3. Meta-Analyses of Cardiovascular Risk  \nSystematic reviews and meta -analyses have synthesized these cohort data to quantify pooled risks. A recent meta -\nanalysis of seven studies (totaling ~1.4 million participants) reported significantly elevated risks for cerebrovascular \ndisease (HR 1.19; 95% CI 1.13 to 1.24), ischemic heart disease (HR 1.35; 95% CI 1.32 to 1.39), MACE (HR 1.15; 95% CI \n1.13 to 1.19) and arrhythmias (HR 1.21; 95% CI 1.17 to 1.25) in women with endometriosis [16]. Notably, no significant \nassociation was observed for heart failure (HR 0.96; 95% CI 0.66 to 1.37) or all -cause mortality in this analysis, \nhighlighting heterogeneity and limited power for HF-specific endpoints [16]. \nEarlier meta -analyses align with these observations. A 2023 review of six cohorts found endometriosis linked to \nincreased ischemic heart disease (HR 1.50; 95% CI 1.37 to 1.65) and cerebrovascular disease (HR 1.17; 95% CI 1.07 to \n1.29), with low heterogenei ty [17]. Another analysis confirmed elevated pooled odds for ischemic heart disease (OR \n1.36; 95% CI 1.32 to 1.40), stroke (OR 1.18; 95% CI 1.13–1.22), and composite CVD (OR 1.16; 95% CI 1.12–1.20), though \nHF data were sparse [18]. These syntheses indicate  modest risk elevations predominantly for atherosclerotic and \ncerebrovascular outcomes, with HF associations less robust and warranting further investigation. \nTo provide a concise comparison of the main findings across study types, Table 1 summarizes the key epidemiological \nevidence presented in this section, including pooled risk estimates and heart failure-specific results where available. \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n12 \nTable 1 Overview of Epidemiological Evidence on Endometriosis and Cardiovascular Risk \nType of \nEvidenc\ne \nKey \nStudies / \nSources \nMain \nCardiovascul\nar Outcomes \nStudied \nRisk Estimates \n(Adjusted) \nHeart \nFailure \n(HF) \nSpecific \nFinding \nOverall \nStrength / \nNotes \nRefer\nences \nNationwi\nde \nRegistrie\ns & Large \nCohorts \nDanish \nnationwid\ne registry \nComposite \nAMI + stroke, \narrhythmias, \nHF \nComposite \nAMI/stroke: HR \n1.15 (1.11 –1.20) \nArrhythmias: HR \n1.21 (1.17–1.25) \nHR 1.11 \n(1.05–1.18) \n– modest \nincrease \nLong follow -up \n(median 16 \nyears); absolute \nrisks small; \nstrong for \narrhythmias \n[12], \n[13] \n \nCanadian \npopulatio\nn-based \ncohort \nCVD hospital \nadmission, \nsecondary \nCVD events, \ncongestive HF \nCVD admission: HR \n1.14 (1.10 –1.19) \nSecondary CVD: HR \n1.26 (1.23–1.30) \nElevated in \nsecondary \noutcomes \n(HR not \nspecified) \nLarge sample \n(>166,000); HF \nmentioned but \nnot primary \nendpoint \n[14] \n \nNurses' \nHealth \nStudy II \n(prospecti\nve cohort) \nMyocardial \ninfarction, \ncomposite \ncoronary \nheart disease \nMI: RR 1.52 (1.17 –\n1.98) Composite \nCHD: RR 1.62 (1.39–\n1.89) \nNot \nspecifically \nreported \nLaparoscopicall\ny confirmed \ncases; \nindependent of \ntraditional risk \nfactors \n[11], \n[15] \nMeta-\nAnalyses \n& \nSystemat\nic \nReviews \nRecent \nmeta-\nanalysis (7 \nstudies, \n~1.4 \nmillion) \nCerebrovascu\nlar disease, \nIHD, MACE, \narrhythmias, \nHF \nCerebrovascular: \nHR 1.19 (1.13–1.24) \nIHD: HR 1.35 (1.32 –\n1.39) MACE: HR \n1.15 (1.13 –1.19) \nArrhythmias: HR \n1.21 (1.17–1.25) \nHF: HR 0.96 \n(0.66–1.37) \n– not \nsignificant \nStrongest \nsignals for IHD, \nstroke, \narrhythmias; \nHF association \nweak / \nunderpowered \n[9], \n[16] \n \n2023 \nreview (6 \ncohorts) \nIschemic \nheart disease, \ncerebrovascu\nlar disease \nIHD: HR 1.50 (1.37 –\n1.65) \nCerebrovascular: \nHR 1.17 (1.07–1.29) \nNot \nspecifically \nreported \nLow \nheterogeneity; \nconsistent with \natherosclerotic \nfocus \n[10] \n \nOther \npooled \nanalyses \nIHD, stroke, \ncomposite \nCVD \nIHD: OR 1.36 (1.32 –\n1.40) Stroke: OR \n1.18 (1.13 –1.22) \nComposite CVD: OR \n1.16 (1.12–1.20) \nHF data \nsparse \nConfirms \nmodest \nelevations; \nlimited HF -\nspecific power \n[18] \nSubgrou\np & \nConfoun\nding \nFactors \nHysterect\nomy / \noophorect\nomy \nAmplifies risk \nvia \npremature \nestrogen \ndecline \nHigher CHD risk in \nsurgical subgroups: \nHR 1.51 (1.34–1.71) \nContributes \nto overall \nCVD \nincrease \nCommon in \nendometriosis; \npartial \nattenuation \nwhen adjusted; \nmajor \nconfounder \n[15], \n[16], \n[19] \n \nAge & \nfollow-up \nduration \nStronger \nrisks in \nyounger \nwomen or \nlonger follow-\nup \nNot quantified \nseparately \nLonger \nfollow-up \nstrengthen\ns HF signal \nRisks appear to \nincrease over \ntime \n[13], \n[15] \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n13 \n \nMendelian \nrandomiza\ntion \nstudies \nLimited \ncausality for \nsome \nendpoints \nNo strong causal \nlink to coronary \nheart disease \nNot \nspecifically \nreported \nSuggests \nresidual \nconfounding; \ncausality not \nfully \nestablished \n[20] \nWhere: AMI - Acute Myocardial Infarction; IHD - Ischemic Heart Disease; CHD - Coronary Heart Disease; HR - Hazard Ratio; CI - Confidence Interval; \nOR - Odds Ratio; CVD - Cardiovascular Disease; RR - Relative Risk (or Risk Ratio); HF - Heart Failure; MACE - Major Adverse Cardiovascular Events \n2.4. Subgroup Analyses and Confounding Factors  \nSubgroup and sensitivity analyses reveal important modifiers. Hysterectomy and/or oophorectomy, common in \nendometriosis management, amplify CVD risks through premature estrogen decline. In one cohort, adjustment for these \nprocedures partially attenuated associations, with higher CHD risk in surgical subgroups (HR 1.51; 95% CI 1.34 to 1.71) \n[15]. Meta-analyses note that treatment -related factors (e.g., early oophorectomy) may confound estimates, as many \nstudies lack full adjustment [16,19]. \nAge at diagnosis and follow -up duration also influence findings; risks appear stronger in younger women or longer -\nterm cohorts [13,15]. Conflicting results from Mendelian randomization studies suggest limited causality for some \nendpoints (e.g., no strong l ink to coronary heart disease), underscoring potential residual confounding [20]. Overall, \nwhile epidemiological evidence supports endometriosis as a contributor to CVD burden, HF-specific data remain modest \nand inconsistent, emphasizing the need for targeted prospective studies. \n3. Chronic Inflammation as a Core Mechanism \n3.1. Overview  \nChronic inflammation constitutes a central pathophysiological feature of endometriosis, extending beyond local \nperitoneal involvement to contribute to systemic effects that may predispose affected women to cardiovascular \ncomplications, including heart failure. This section examines the inflammatory milieu in endometriosis, focusing on key \npro-inflammatory mediators, their spillover from peritoneal sources into circulation, associated biomarkers of systemic \nactivation, and the pathways through which sustaine d inflammation promotes endothelial injury, atherosclerosis, and \nadverse cardiac remodeling. Evidence from biomarker studies and mechanistic reviews illustrates how these processes \nparallel those in established inflammatory conditions linked to increased heart failure risk, underscoring inflammation \nas a plausible bridge between endometriosis and cardiac vulnerability. \n3.2. Pathophysiology of Systemic Inflammation in Endometriosis  \nEndometriosis is characterized by a pro -inflammatory peritoneal microenvironment, with ectopic endometrial tissue \neliciting recruitment and activation of immune cells that release elevated levels of pro-inflammatory cytokines [21]. Key \nmediators include in terleukin-6 (IL -6), tumor necrosis factor -α (TNF -α), and interleukin -1β (IL -1β) which are \nconsistently higher in peritoneal fluid of affected women compared to controls which contribute to local tissue \nremodeling and pain [22]. These cytokines produced by macrophages, endometriotic stromal cells and mesothelial cells \npromote a self-sustaining inflammatory cycle through autocrine and paracrine signaling. \nSystemic spillover occurs as peritoneal cytokines and inflammatory mediators enter the circulation, leading to low -\ngrade chronic inflammation detectable in serum [23]. Studies demonstrate elevated circulating IL -6, TNF-α, and IL-1β \nin women with endometriosis, particularly in advanced stages, correlating with disease severity and symptom burden \n[24]. This transition from localized to systemic inflammation is facilitated by increased vascular permeability in \nendometriotic lesions and peritoneal mesothelial activation, allowing diffusion of soluble factors into the bloodstream \n[25]. Consequently, affected women exhibit persistent immune activation that may extend beyond gynecological \nconfines. \n3.3. Inflammation-Driven Endothelial Dysfunction and Atherosclerosis  \nChronic inflammation in endometriosis induces endothelial dysfunction, a critical early step in atherogenesis, through \ncytokine-mediated impairment of nitric oxide bioavailability and increased oxidative stress [21,26]. Pro-inflammatory \nmediators such as IL-6 and TNF-α promote expression of adhesion molecules on endothelial cells, facilitating leukocyte \nrecruitment and plaque initiation [23]. Non-invasive assessments reveal reduced reactive hyperemia index (indicating \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n14 \nendothelial impairment) and elevated advanced glycation end -products in skin (reflecting arterial stiffness) among \nwomen with endometriosis compared to controls [24]. \nThese vascular changes align with accelerated atherosclerosis progression, as systemic inflammation fosters lipid \noxidation, foam cell formation, and plaque instability [22]. Observational data link endometriosis -associated \ninflammation to higher prevalence of subclinical atherosclerotic markers, including increased intima -media thickness \nand coronary artery calcification in some cohorts [27]. The interplay between persistent cytokine elevation and \nendothelial injury thus provides a mechanistic basis for th e modest but reproducible cardiovascular risk elevations \nobserved epidemiologically. \nThe interconnected mechanisms underlying the endometriosis -cardiovascular disease link are illustrated in Figure 1 \nwhich is a schematic diagram highlighting inflammation, oxidative stress and endothelial pathways \n \nFigure 1 Schematic Diagram of Pathophysiological Links Between Endometriosis and CVD [53] \n3.4. Links to Cardiac Remodeling and Heart Failure Pathways  \nSustained systemic inflammation contributes to cardiac remodeling through cytokine effects on cardiomyocytes and \nfibroblasts thereby promoting fibrosis, hypertrophy and diastolic dysfunction which are hallmarks of heart failure with \npreserved ejection frac tion (HFpEF) which predominates in women [28]. Elevated IL -6 and TNF -α activate signaling \npathways (e.g., NF -κB, JAK/STAT) that drive myocardial inflammation and extracellular matrix deposition, impairing \nventricular compliance [29]. Biomarker studies in endometriosis cohorts show increased C-reactive protein (CRP) and \noxidative stress markers, which correlate with endothelial dysfunction and predict adverse cardiac outcomes in broader \ninflammatory contexts [30]. \nParallels exist with other chronic inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel \ndisease, where similar cytokine profiles (IL -6, TNF-α) confer elevated heart failure risk via myocardial inflammation \nand remodeling [31]. In end ometriosis, the chronicity of inflammation may amplify these effects, particularly in the \npresence of comorbidities or surgical interventions that exacerbate systemic burden [32]. While direct cardiac \ninvolvement remains understudied, these overlapping pat hways position inflammation as a plausible contributor to \nheart failure susceptibility in endometriosis. \n \n\n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n15 \n4. Estrogen Dysregulation and Its Cardiovascular Implications \n4.1. Overview  \nEstrogen plays a pivotal yet complex role in endometriosis, where local overproduction and systemic dysregulation \ncontribute to disease persistence and potentially broader health sequelae. This section explores the hormonal landscape \nof endometriosis, emph asizing excessive local estrogen synthesis in ectopic lesions, progesterone resistance and the \ndualistic cardiovascular effects of estrogen which is protective under physiological conditions but potentially \ndetrimental when dysregulated or suppressed. Evid ence from clinical and mechanistic studies highlights how these \nalterations influence vascular tone, lipid metabolism, and cardiac electrophysiology, alongside the cardiovascular \nconsequences of therapeutic interventions that modulate estrogen levels. \n4.2. Estrogen Excess and Progesterone Resistance in Endometriotic Lesions  \nEndometriotic lesions exhibit autonomous estrogen production through upregulated aromatase expression, leading to \nelevated local estradiol concentrations that sustain tissue proliferation and inflammation independent of ovarian \ncycling [34]. This intracrine estrogen synthesis, coupled with reduced inactivation pathways, creates a hyperestrogenic \nmilieu within implants, perpetuating the disease process [35]. Progesterone resistance further exacerbates this \nimbalance, as endometriotic tissue demonstrates dimi nished responsiveness to progesterone's antiproliferative and \nanti-inflammatory actions, often due to altered receptor isoforms or signaling defects [34,36]. \nThese hormonal perturbations extend systemically in some patients, with evidence of altered circulating estrogen \nmetabolites and impaired luteal phase progesterone support [35]. The resulting imbalance favors pro -inflammatory \ncytokine release and oxidative  stress, which may indirectly influence distant tissues, including the vasculature [37]. \nSuch dysregulation underscores why endometriosis manifests as a hormone -dependent disorder with potential \nextrapelvic ramifications. \n4.3. Dual Role of Estrogen in Cardiovascular Protection and Dysregulation  \nEstrogen exerts well -documented protective effects on the cardiovascular system under physiological conditions, \nincluding promotion of vasodilation via endothelial nitric oxide synthase activation, inhibition of smooth muscle \nproliferation, and favorable m odulation of lipid profiles [35]. In premenopausal women, these actions contribute to \nlower atherosclerosis risk compared to age -matched men [38]. However, in endometriosis, chronic local estrogen \nexcess and associated inflammation may override these benefits, potentially promoting endothelial dysfunction through \nheightened oxidative stress and pro-thrombotic tendencies [34]. \nDysregulated estrogen signaling such as altered receptor expression or metabolite profiles can shift toward adverse \nvascular effects, including increased arterial stiffness and impaired flow -mediated dilation observed in some \nendometriosis cohorts [35]. These changes parallel mechanisms in other hyperestrogenic states where excess estrogen \ncontributes to inflammation -driven vascular injury [37]. The net cardiovascular impact thus depends on the balance \nbetween protective systemic effects and localized pathological overdrive. \nTable 2 contrasts the physiological protective effects of estrogen with its actions in endometriosis and the resulting \ncardiovascular consequences. \nTable 2 Comparison of Estrogen Dysregulation Pathways and Cardiovascular Implications in Endometriosis \nContext Estrogen Level \n/ Action \nVascular \nEffect \nLipid \nProfile \nEffect \nCardiac Effect Clinical \nImplication in \nEndometriosi\ns \nReferenc\ne \nPhysiological \n(premenopausal\n) \nNormal \ncirculating \nlevels \nVasodilation \n(eNOS \nactivation), \nanti-\natherogenic \nFavorable \n(↑HDL, \n↓LDL) \nProtective \nagainst \nremodeling \nNormal \nprotection lost \nin some \npatients \n[35], [38] \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n16 \nLocal in \nendometriotic \nlesions \nExcessive \nintracrine \nproduction \n(aromatase ↑) \nPro-\ninflammator\ny, oxidative \nstress \nNot directly \naffected \nIndirect via \ninflammation \nSustains local \ndisease and \nsystemic \nspillover \n[34], [35] \nSystemic \ndysregulation \nErratic / altered \nmetabolites \nEndothelial \ndysfunction, \n↑ stiffness \nPotentially \natherogenic \nArrhythmogeni\nc potential \nParadoxical \nloss of \nprotection \n[34], [43] \nPost-GnRH \nagonist / \nsurgical \nmenopause \nSuppression \n(hypoestrogenic\n) \nLoss of \nvasodilation, \n↑ stiffness \nDyslipidemi\na (↑LDL, \n↓HDL) \nIncreased \ncardiac strain \nAmplifies CVD \nrisk \n[33], [36] \nWhere: eNOS - Endothelial Nitric Oxide Synthase; LDL - Low-Density Lipoprotein; GnRH - Gonadotropin-Releasing Hormone;‘↑’ – Increase; HDL - \nHigh-Density Lipoprotein; ‘↓’ – decrease; HFpEF - Heart Failure with Preserved Ejection Fraction \nThe effects of estrogen in endometriosis is protective under normal conditions but potentially detrimental when \ndysregulated, this is depicted in Figure 2 which is a schematic overview of mechanisms linking endometriosis to \ncardiovascular disease \n \nFigure 2 Mechanisms linking endometriosis with cardiovascular disease [23]. \n4.4. Effects of Treatments Altering Estrogen Levels and Cardiovascular Risk  \nTherapeutic suppression of estrogen via gonadotropin -releasing hormone (GnRH) agonists or antagonists induces a \nhypoestrogenic state to regress lesions, but this comes with metabolic and cardiovascular trade -offs [36]. GnRH \ntherapies suppress ovarian estro gen production, leading to adverse changes such as dyslipidemia, insulin resistance, \nand increased arterial stiffness, which elevate risks for atherosclerosis and ischemic events in prolonged use [39]. \nObservational data indicate heightened cardiovascular vulnerability in patients receiving long -term GnRH analogues, \nparticularly through estrogen withdrawal effects on endothelial function and lipid metabolism [37]. \nAdd-back hormone regimens (low-dose estrogen/progestin) aim to mitigate hypoestrogenic sequelae like bone loss and \nvasomotor symptoms, yet their impact on cardiovascular risk remains incompletely defined [33]. Surgical interventions, \nsuch as oophorectomy, accelerate estrogen decline and associate with amplified CVD risk in endometriosis patients \n\n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n17 \n[34]. These findings emphasize the need for individualized hormonal management that weighs gynecological benefits \nagainst potential long-term vascular consequences. \n5. Cardiometabolic Overlap: Metabolic Syndrome, Insulin Resistance, and Dyslipidemia \n5.1. Overview  \nCardiometabolic disturbances represent an important intersection between endometriosis and cardiovascular \nvulnerability, with shared pathways involving chronic inflammation, hormonal imbalance, and metabolic dysregulation \npotentially contributing to insulin resistance, dyslipidemia, central adiposity, and components of metabolic syndrome. \nThis section reviews epidemiological associations between endometriosis and metabolic syndrome or its elements, \nmechanistic links through inflammation -driven insulin resis tance and lipid alterations, and implications for heart \nfailure—particularly the preserved ejection fraction phenotype prevalent in women—where metabolic stress amplifies \ndiastolic dysfunction and cardiac strain. \n5.2. Association with Metabolic Syndrome Components  \nWomen with endometriosis exhibit a higher prevalence of metabolic syndrome compared to unaffected controls, as \nevidenced by population-based and cross-sectional studies. In one large cohort, the adjusted odds ratio for metabolic \nsyndrome was 1.99 (95% CI 1.20 to 3.30), driven primarily by increased central obesity (high waist circumference) and \nlow HDL-cholesterol [40]. Similar findings from NHANES-derived analyses report adjusted odds of metabolic syndrome \nranging from 1.55 (95% CI 1.01 to 2.35) to higher in specific subgroups, though associations may attenuate after \naccounting for surgical history such as hysterectomy [41]. \nDyslipidemia emerges consistently, with endometriosis linked to atherogenic profiles including elevated triglycerides \nand reduced HDL [42]. Cross-sectional data indicate endometriosis patients have higher odds of low HDL (adjusted OR \n2.07; 95% CI 1.02 to 4.20) and central adiposity, independent of age and lifestyle factors [40]. These components cluster \nto form metabolic syndrome in a subset of patients, potentially exacerbating systemic inflammation and cardiovascular \nrisk beyond gynecological manifestations. \n5.3. Insulin Resistance Mechanisms: Inflammation and Estrogen Interplay  \nInsulin resistance in endometriosis arises from chronic low -grade inflammation, where elevated cytokines (e.g., IL -6, \nTNF-α) impair insulin signaling in adipose and muscle tissue, promoting glucose intolerance and hyperinsulinemia [42]. \nEstrogen dysregulat ion amplifies this process: local excess in lesions sustains inflammatory cycles, while systemic \nfluctuations may contribute to adipose tissue dysfunction and oxidative stress, further driving resistance [43]. \nMechanistic studies highlight how inflammation  disrupts glucose uptake and lipid handling, creating a feedback loop \nwith progesterone resistance that favors metabolic derangements. \nCross-sectional evidence supports these pathways, with endometriosis cohorts showing altered insulin sensitivity \nmarkers correlated with disease severity [41]. Such resistance aligns with broader cardiometabolic phenotypes, where \npersistent metabolic stress fosters endothelial dysfunction and vascular stiffness—precursors to cardiac strain. \n5.4. Links to Heart Failure and Cardiometabolic Indices  \nThe cardiometabolic index (CMI), integrating triglycerides-to-HDL ratio and waist-to-height ratio, serves as a surrogate \nfor metabolic dysfunction and visceral adiposity. Recent NHANES analyses demonstrate positive associations between \nhigher CMI and endom etriosis prevalence, with fully adjusted odds ratios of 1.21 to 1.78 for the highest vs. lowest \nquartiles, and linear increases beyond CMI thresholds (~0.67) yielding ~20% risk elevation per unit increment [37,38]. \nThese findings suggest CMI as a potential screening tool for metabolic burden in endometriosis. \nIn the context of heart failure, particularly HFpEF, cardiometabolic overlap predisposes women through inflammation, \ninsulin resistance, and dyslipidemia -driven myocardial remodeling and diastolic impairment [44]. Endometriosis -\nrelated metabolic changes may contribute to this phenotype by amplifying systemic stress, though direct longitudinal \ndata remain limited. Addressing these overlaps through lifestyle or targeted interventions could mitigate progression \nto cardiac complications. \nTable 3 summarizes the cardiometabolic abnormalities most frequently reported in women with endometriosis and \ntheir proposed mechanistic contributions to heart failure development. \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n18 \nTable 3 Cardiometabolic Features in Endometriosis and Their Link to Heart Failure Risk \nCardiometabolic \nFeature \nPrevalence / \nAssociation in \nEndometriosis \nKey \nSupporting \nData \nProposed Mechanism \nLinking to HF \nStrength \nof \nEvidence \nReference \nMetabolic \nsyndrome \nHigher prevalence (OR \n1.55–1.99) \nAdjusted OR \n1.99 (1.20 –\n3.30) \nInflammation + insulin \nresistance → myocardial \nstrain \nModerate [40], [41] \nInsulin resistance Increased markers Correlated \nwith disease \nseverity \nLipotoxicity + \ninflammation → diastolic \ndysfunction \nModerate [42], [43] \nDyslipidemia (low \nHDL, high TG) \nHigher odds of low HDL \n(OR 2.07) \nConsistent \nacross \ncohorts \nAtherogenic profile → \nendothelial/myocardial \nstress \nStrong [40], [42] \nCentral adiposity \n/ elevated CMI \nPositive association with \nCMI \nAdjusted OR \n1.21–1.78 \n(highest vs \nlowest \nquartile) \nVisceral fat → systemic \ninflammation → HFpEF \nEmerging [37], [38], \n[39] \nHFpEF \npredisposition \nIndirect via \nmetabolic/inflammatory \noverlap \nParallels in \nwomen with \nMetS \nDiastolic dysfunction \nfrom metabolic stress \nIndirect / \nplausible \n[44] \nWhere: CMI — Cardiometabolic Index; OR — Odds Ratio;HDL — High-Density Lipoprotein; TG — Triglycerides; HF — Heart Failure; MetS — \nMetabolic Syndrome; HFpEF — Heart Failure with Preserved Ejection Fraction;‘→’ – which leads to… \n6.  Integrated Mechanisms and Emerging Hypotheses \n6.1. Overview  \nThe pathways linking endometriosis to heart failure risk converge through intertwined processes of chronic \ninflammation, estrogen dysregulation and cardiometabolic alterations creating potential feedback loops that amplify \nsystemic effects. This section in tegrates evidence from preceding discussions, examining how these elements interact \nto promote endothelial injury, metabolic stress, and cardiac remodeling. It also addresses emerging hypotheses on \ndirect myocardial involvement and persistent gaps in HF -specific mechanistic data with implications for future \nbiomarker development and risk stratification. \n6.2. Synthesis of Inflammation, Estrogen Dysregulation and Cardiometabolic Factors  \nChronic inflammation in endometriosis, marked by elevated IL -6, TNF -α and IL -1β intersects with estrogen \noverproduction in ectopic lesions to sustain a pro -inflammatory state that extends systemically [45]. Local estrogen \nexcess drives cytokine release and oxidative stress, while systemic fluctuations may enhance vascular inflammation and \nimpair endothelial function, forming a self -reinforcing cycle [45,50]. This interplay parallels cardiometabolic \ndisturbances, where inflammation -induced insulin resistance  and dyslipidemia (e.g., low HDL, high triglycerides) \nfurther exacerbate oxidative damage and atherogenesis [46,47]. \nCardiometabolic index elevations in endometriosis cohorts reflect this overlap, with higher CMI associating with \nincreased disease odds through visceral adiposity and lipid dysregulation that amplify inflammatory signaling [46]. \nEstrogen's dual role which are protective via nitric oxide pathways under normal conditions but pro -inflammatory \nwhen dysregulated contributes to arterial stiffness and plaque instability, particularly when compounded by metabolic \nfactors [45,48]. These integrated mechanisms suggest  a vicious cycle whereby inflammation sustains estrogen \nimbalance, metabolic stress perpetuates cytokine production, and the resulting endothelial/myocardial strain \nheightens HF vulnerability. \n6.3. Potential Direct Cardiac Involvement and Vicious Cycles  \nEmerging evidence points to direct effects on cardiac tissue, as sustained cytokines and oxidative stress from \nendometriosis may promote myocardial inflammation, fibrosis, and diastolic dysfunction characteristic of HFpEF \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n19 \n[49,51]. Estrogen signaling alterations could influence cardiomyocyte function and extracellular matrix remodeling, \nwhile metabolic overload from insulin resistance adds lipotoxic stress to the myocardium [52]. Animal models and \nlimited human data support these pathways, though causality remains inferred from parallels in other inflammatory \nconditions [50]. \nSuch vicious cycles where inflammation drives estrogen dysregulation which in turn worsens metabolic profiles and \nendothelial injury may explain amplified risks in subgroups with surgical estrogen depletion or prolonged disease \nduration [48]. However, heterogeneity in observational data underscores that these interactions are likely modulated \nby genetic, lifestyle, and treatment factors. \n6.4. Gaps and Future Directions  \nDespite converging evidence, HF -specific longitudinal studies are scarce, with most data derived from broader CVD \nendpoints or cross -sectional associations [49]. Direct mechanistic investigations, including cardiac imaging in \nendometriosis cohorts or targe ted animal models of lesion -induced inflammation, are needed to clarify myocardial \ninvolvement [45]. Biomarker panels integrating CRP, IL -6, estrogen metabolites, and CMI could aid risk stratification, \npotentially identifying high-risk patients for early intervention [46,47]. \nProspective cohorts with serial assessments of inflammatory, hormonal and metabolic markers would strengthen \ncausal inference and guide multidisciplinary management. Targeted therapies addressing shared pathways such as anti-\ninflammatory agents or optimize d hormonal modulation represent promising avenues to mitigate progression to \ncardiac complications. \n7. Conclusion  \nEndometriosis which is long viewed primarily as a gynecological condition increasingly emerges as a contributor to \nsystemic health risks, including modest but clinically meaningful elevations in cardiovascular disease burden and in \nparticular heart failure susceptibility. The mechanistic threads such as chronic low -grade inflammation with cytokine \nspillover, estrogen dysregulation favoring pro -inflammatory and vascular effects and cardiometabolic overlap \nmanifesting as insulin resistance, dyslipidemia and m etabolic syndrome components interweave to create pathways \nthat promote endothelial dysfunction, atherosclerosis, myocardial remodeling and diastolic impairment especially in \nthe context of heart failure with preserved ejection fraction. These shared proce sses, often amplified by surgical \ninterventions or prolonged disease duration explain why affected women may face heightened long -term cardiac \nvulnerability despite the generally modest hazard ratios reported in epidemiological syntheses. \nRecognizing endometriosis as an underrecognized risk factor for heart failure carries important clinical implications. \nRoutine cardiovascular risk assessment encompassing blood pressure, lipid profiles, glucose tolerance, inflammatory \nmarkers and cardiomet abolic indices should be considered in women with confirmed or suspected endometriosis \nparticularly those with advanced disease, early surgical menopause or additional traditional risk factors. \nMultidisciplinary collaboration between gynecologists, cardiol ogists and endocrinologists would facilitate timely \nidentification and mitigation of modifiable elements, potentially through lifestyle optimization, judicious hormonal \nmanagement or targeted anti-inflammatory strategies. \nSubstantial gaps persist, especially in prospective longitudinal data tracking heart failure incidence, direct myocardial \neffects and intervention efficacy. Addressing these through dedicated cohorts, advanced imaging and mechanistic \nstudies remains essent ial to refine risk stratification and inform preventive approaches. Ultimately, broadening the \nclinical lens on endometriosis beyond pelvic symptoms may improve long -term outcomes for millions of women \nworldwide. \nCompliance with ethical standards \nAcknowledgements \nThe authors recognize the hard work of all the scholars and colleagues who together wrote and refined this review \npaper. The team carried out this work with their intellectual and academic efforts, without any aid or funding from \noutside sources like individuals, institutions, or organizations. \n \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n20 \nDisclosure of conflict of interest \nThe authors confirm they have no financial interests or personal connections that might have affected the research \nshared in this paper. \nReferences \n[1] Parasar P, Ozcan P, Terry KL. Endometriosis: Epidemiology, Diagnosis and Clinical Management. Current \nObstetrics and Gynecology Reports. 2017;6(1):34-41. doi:10.1007/s13669-017-0195-1. \n[2] Harder C, Velho RV, Brandes I, Sehouli J, Mechsner S. Assessing the true prevalence of endometriosis: A narrative \nreview of literature data. International Journal of Gynecology & Obstetrics. 2024;167(3):883 -900. \ndoi:10.1002/ijgo.15845. \n[3] Moradi Y, Shams -Beyranvand M, Khateri S, Gharahjeh S, Tehrani S, Varse F, et al. A systematic review on the \nprevalence of endometriosis in women. Indian Journal of Medical Research. 2021;154(3):446 -454. \ndoi:10.4103/ijmr.IJMR_406_20. \n[4] World Health Organization. Endometriosis fact sheet. 2025. Available from: https://www.who.int/news-\nroom/fact-sheets/detail/endometriosis. \n[5] De Corte P, Klinghardt M, von Stockum S, Heinemann K. Time to diagnose endometriosis: current status, \nchallenges and regional characteristics - a systematic literature review. BJOG: An International Journal of \nObstetrics & Gynaecology. 2025;132(2):118-130. doi:10.1111/1471-0528.17973. \n[6] Regitz-Zagrosek V. Sex and Gender Differences in Heart Failure. International Journal of Heart Failure. \n2020;2(3):157-169. doi:10.36628/ijhf.2020.0010. \n[7] Sotomi Y, Hikoso S, Nakatani D, Mizuno H, Okada K, Dohi T, et al. Sex differences in heart failure with preserved \nejection fraction. Journal of the American Heart Association. 2021;10(5):e018574. \ndoi:10.1161/JAHA.120.018574. \n[8] Ferreira C, Trindade F, Ferreira R, Neves JS, Leite -Moreira A, Amado F, et al. Sexual dimorphism in cardiac \nremodeling: the molecular mechanisms ruled by sex hormones in the heart. Journal of Molecular Medicine. \n2022;100(2):245-267. doi:10.1007/s00109-021-02163-2. \n[9] Saad M, Ansari I, Ibrahim ZS, Batool RM, Ahsan SI, Arshad MS, et al. Increased risk of cardiovascular disease in \nwomen with endometriosis: A systematic review and meta -analysis. European Journal of Obstetrics & \nGynecology and Reproductive Biology. 2025;312:114081. doi:10.1016/j.ejogrb.2025.114081. \n[10] do Couto CP, Policiano C, Pinto FJ, Brito D, Caldeira D. Endometriosis and cardiovascular disease: A systematic \nreview and meta-analysis. Maturitas. 2023;171:45-52. doi:10.1016/j.maturitas.2023.03.004. \n[11] Mu F, Rich-Edwards J, Rimm EB, Spiegelman D, Missmer SA. Endometriosis and Risk of Coronary Heart Disease. \nCirculation: Cardiovascular Quality and Outcomes. 2016;9(3):257 -264. \ndoi:10.1161/CIRCOUTCOMES.115.002224. \n[12] Havers-Borgersen E, Hartwell D, Ekelund C, Butt JH, Østergaard L, Holgersson C, et al. Endometriosis and long -\nterm cardiovascular risk: a nationwide Danish study. European Heart Journal. 2024;45(44):4734 -4743. \ndoi:10.1093/eurheartj/ehae563. \n[13] Chen DY, Li CY, Hsieh MJ, Chen CC, Hsieh IC, Chen TH, et al. Predictors of subsequent myocardial infarction, stroke, \nand death in stable post -myocardial infarction patients: A nationwide cohort study. European Heart Journal: \nAcute Cardiovascular Care. 2019;8(7):634-642. doi:10.1177/2048872618803704. \n[14] Blom JN, Gotlib Conn L, Maclagan LC, Austin PC, Chu A, Tu JV. Endometriosis and cardiovascular disease: a \npopulation-based cohort study. CMAJ Open. 2023;11(2):E227-E236. doi:10.9778/cmajo.20220141. \n[15] Okoth K, Chandan JS, Marshall T, Thangaratinam S, Thomas GN, Nirantharakumar K, et al. Association between \nthe reproductive health of young women and cardiovascular disease in later life: umbrella review. BMJ. \n2020;371:m3963. doi:10.1136/bmj.m3963. \n[16] Bulun SE, Gurates B, Fang Z, Tamura M, Sebastian S, Zhou J, et al. Mechanisms of excessive estrogen formation in \nendometriosis. Journal of Reproductive Immunology. 2002;55(1-2):21-33. doi:10.1016/s0165-0378(01)00099-\n3. \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n21 \n[17] Cucinella L, Odone A, Nappi RE. Reproductive History and Cardio -Metabolic Risk in the Postmenopausal Age. \nSeminars in Reproductive Medicine. 2025;43(2):73-84. doi:10.1055/s-0045-1811965. \n[18] Cavadias I, Polymeropoulou C, Vlachou E, Valsamakis G, Mastorakos G, Siristatidis C, et al. Risk of cardiovascular \ndisease and mortality among women with endometriosis: A systematic review and meta -analysis. Acta \nObstetricia et Gynecologica Scandinavica. 2026;105(2):225-237. doi:10.1111/aogs.14999. \n[19] Okoli U, Akingbade O, Okoli C, Okoli C. Endometriosis and Risk of Cardiovascular Disease: Systematic Review and \nMeta-Analysis. Journal of Women's Health. 2023;32(10):1065-1076. doi:10.1089/jwh.2023.0091. \n[20] Holmes MV, Ala -Korpela M, Smith GD. Mendelian randomization in cardiometabolic disease: challenges in \nevaluating causality. Nature Reviews Cardiology. 2017;14(10):577-590. doi:10.1038/nrcardio.2017.78. \n[21] Tan J, Taskin O, Iews M, Lee AJ, Kan A, Rowe T, et al. Atherosclerotic cardiovascular disease in women with \nendometriosis: a systematic review of risk factors and prospects for early surveillance. Reproductive \nBioMedicine Online. 2019;39(6):1007-1016. doi:10.1016/j.rbmo.2019.08.004. \n[22] Parsa S, Noroozpoor R, Dehghanbanadaki H, Khateri S, Moradi Y. Endometriosis and risk of cardiovascular \ndisease: a systematic review and meta -analysis. BMC Public Health. 2025;25(1):245. doi:10.1186/s12889 -025-\n21486-0. \n[23] Szpila G, Szczotka J, Suchodolski A, Szulik M. Endometriosis and Cardiovascular Disease: Exploring \nPathophysiological Interconnections and Risk Mechanisms. Diagnostics. 2025;15(12):1458. \ndoi:10.3390/diagnostics15121458. \n[24] Smyk JM, Danielecka Z, Kotowska M, Zawadka M, Andruszkiewicz P, Grąt M, et al. Cardiovascular risks and \nendothelial dysfunction in reproductive -age women with endometriosis. Scientific Reports. 2024;14(1):24127. \ndoi:10.1038/s41598-024-73841-7. \n[25] Bourdon M, Santulli P, Jeljeli M, Vannuccini S, Marcellin L, Doridot L, et al. Immunological changes associated with \nadenomyosis: a systematic review. Human Reproduction Update. 2021;27(1):108 -129. \ndoi:10.1093/humupd/dmaa050. \n[26] Gibson DA, Simitsidellis I, Collins F, Saunders PT. Endometrial intracrinology: oestrogens, androgens and \nendometrial disorders. International Journal of Molecular Sciences. 2018;19(10):3276. \ndoi:10.3390/ijms19103276. \n[27] Taskin O, Rikhraj K, Tan J, Sedlak T, Rowe TC, Bedaiwy MA. Link between endometriosis, atherosclerotic \ncardiovascular disease, and the health of women midlife. Journal of Minimally Invasive Gynecology. \n2019;26(5):781-784. doi:10.1016/j.jmig.2019.02.016. \n[28] Sotomi Y, Hikoso S, Nakatani D, Mizuno H, Okada K, Dohi T, et al. Sex differences in heart failure with preserved \nejection fraction. Journal of the American Heart Association. 2021;10(5):e018574. \ndoi:10.1161/JAHA.120.018574. \n[29] Kaur G, Lau E. Sex differences in heart failure with preserved ejection fraction: From traditional risk factors to \nsex-specific risk factors. Women's Health. 2022;18:17455057221140209. doi:10.1177/17455057221140209. \n[30] Gleason JL, Thoma ME, Zukerman Willinger N, Shenassa ED. Endometriosis and uterine fibroids and their \nassociations with elevated C -reactive protein and leukocyte telomere length among a representative sample of \nUS women: data from the National Health and N utrition Examination Survey, 1999 –2002. Journal of Women's \nHealth. 2022;31(7):1020-1028. doi:10.1089/jwh.2021.0325. \n[31] Larrosa Pardo F, Bondesson E, Schelin ME, Jöud A. A diagnosis of rheumatoid arthritis, endometriosis or IBD is \nassociated with later onset of fibromyalgia and chronic widespread pain. European Journal of Pain. \n2019;23(8):1563-1573. doi:10.1002/ejp.1432. \n[32] Muruet W, Rudd A, Wolfe CDA, Douiri A. Long-term survival after intravenous thrombolysis for ischemic stroke: \na propensity score -matched cohort with up to 10 -year follow -up. Stroke. 2018;49(3):607 -613. \ndoi:10.1161/STROKEAHA.117.019889. \n[33] Taylor HS, Giudice LC, Lessey BA, Horne AW, Diamond MP, Kiesel L, et al. Treatment of Endometriosis-Associated \nPain with Elagolix, an Oral GnRH Antagonist. The New England Journal of Medicine. 2017;377(1):28 -40. \ndoi:10.1056/NEJMoa1700089. \n[34] Chantalat E, Valera MC, Vaysse C, Noirrit E, Rusidze M, Weyl A, et al. Estrogen receptors and endometriosis. \nInternational Journal of Molecular Sciences. 2020;21(8):2815. doi:10.3390/ijms21082815. \n\nInternational Journal of Biological and Pharmaceutical Sciences Archive, 2026, 11(02), 009-022 \n \n22 \n[35] Kinugasa S, Shinohara K, Wakatsuki A. Increased asymmetric dimethylarginine and enhanced inflammation are \nassociated with impaired vascular reactivity in women with endometriosis. Atherosclerosis. 2011;219(2):784 -\n788. doi:10.1016/j.atherosclerosis.2011.08.004. \n[36] Etezadi A, Marashi SM, Nazari L, Sina M, Nasab FS, Amirlatifi S, et al. Effects of GnRH agonists and antagonists on \ncardiovascular and metabolic systems in adults: Mechanistic pathways and risk management. Biomedicine & \nPharmacotherapy. 2025;193:118860. doi:10.1016/j.biopha.2025.117054. \n[37] Wang J, Wang X, Li Y, et al. Association between cardiometabolic Index (CMI) and endometriosis: a cross-sectional \nstudy on NHANES. Lipids in Health and Disease. 2024;23(1):311. doi:10.1186/s12944-024-02311-7. \n[38] Hou J, Chen W, Wang R, Huang X, Cao X, Wang X. Relationship between Cardiometabolic index and endometriosis \nin a US nationally representative sample: results from NHANES 1999 -2006. Frontiers in Endocrinology. \n2024;15:1450965. doi:10.3389/fendo.2024.1450965. \n[39] Lv Y, Tang Z, Su L, Tian X. Inverse association between cardiometabolic index and endometriosis in women of \nreproductive age: A cross -sectional, population -based study. Journal of International Medical Research. \n2026;54(2):03000605261422932. doi:10.1177/03000605261422932. \n[40] Saei Ghare Naz M, Noroozzadeh M, Ardebili SN, Mousavi M, Azizi F, Ramezani Tehrani F. Cardio -Metabolic Risk \nProfile of Women With Endometriosis: A Population -Based Study. Endocrinology, Diabetes & Metabolism. \n2024;7(6):e70008. doi:10.1002/edm2.70008. \n[41] Li B, Zhang Y, Zhang L, Zhang L. Association between endometriosis and metabolic syndrome: a cross -sectional \nstudy based on the National Health and Nutrition Examination Survey data. Gynecological Endocrinology. \n2023;39(1):2254844. doi:10.1080/09513590.2023.2254844. \n[42] SenthilKumar G, Katunaric B, Bordas -Murphy H, Sarvaideo J, Freed JK. Estrogen and the vascular endothelium: \nthe unanswered questions. Endocrinology. 2023;164(6):bqad079. doi:10.1210/endocr/bqad079. \n[43] Greygoose E, Metharom P, Kula H, Seckin TK, Seckin TA, Ayhan A, et al. The Estrogen –Immune interface in \nendometriosis. Cells. 2025;14(1):58. doi:10.3390/cells14010058. \n[44] Gorica E, Geiger MA, Di Venanzio L, Atzemian N, Kleeberger JA, Grigorian D, et al. Cardiometabolic heart failure \nwith preserved ejection fraction: from molecular signatures to personalized treatment. Cardiovascular \nDiabetology. 2025;24(1):265. doi:10.1186/s12933-025-02650-9. \n[45] Amidifar S, Jafari D, Mansourabadi AH, Sadaghian S, Esmaeilzadeh A. Immunopathology of endometriosis, \nmolecular approaches. American Journal of Reproductive Immunology. 2025;93(3):e70056. \ndoi:10.1111/aji.70056. \n[46] Zhang J, Zhang Q, Chu T, Chen X, Zhou H, Xu D, Dong C, Wu Y. Association between visceral adiposity index and \nendometriosis: a population -based study. Frontiers in Nutrition. 2025;12:1602288. \ndoi:10.3389/fnut.2025.1602288. \n[47] Liu L, Su G, Rao J, Peng J, Lin X, Huang Y, et al. Association between atherogenic index of plasma and \nendometriosis: evidence from NHANES 1999 –2006. International Journal of Women's Health. 2025;17:2175 -\n2184. doi:10.2147/IJWH.S512345. \n[48] Monteiro R, Teixeira D, Calhau C. Estrogen signaling in metabolic inflammation. Mediators of Inflammation. \n2014;2014:615917. doi:10.1155/2014/615917. \n[49] Paulus WJ, Zile MR. From systemic inflammation to myocardial fibrosis: the heart failure with preserved ejection \nfraction paradigm revisited. Circulation Research. 2021;128(10):1451 -1467. \ndoi:10.1161/CIRCRESAHA.121.318082. \n[50] Steiner BM, Berry DC. The regulation of adipose tissue health by estrogens. Frontiers in Endocrinology. \n2022;13:889923. doi:10.3389/fendo.2022.889923. \n[51] Marchandot B, Curtiaud A, Matsushita K, Trimaille A, Host A, Faller E, et al. Endometriosis and cardiovascular \ndisease. European Heart Journal Open. 2022;2(1):oeac001. doi:10.1093/ehjopen/oeac001. \n[52] Petraglia F, Vannuccini S, Donati C, Jeljeli M, Bourdon M, Chapron C. Endometriosis and comorbidities: molecular \nmechanisms and clinical implications. Trends in Molecular Medicine. 2025. doi:10.1016/j.molmed.2025.09.002. \n[53] Marchandot B, Curtiaud A, Matsushita K, Trimaille A, Host A, Faller E, Garbin O, Akladios C, Jesel L, Morel O. \nEndometriosis and cardiovascular disease. European heart journal open. 2022;2(1):oeac001.  \ndoi:10.1093/ehjopen/oeac001","source_license":"CC0","license_restricted":false}