Endometriosis, Anxiety, Allergic Rhinoconjunctivitis, and Asthma: A Population-Based Study

We conducted a cross-sectional study using the Healthcare Cost and Utilization Project (HCUP) databases from 2007 to 2014, focusing on adult women who sought care at participating hospitals during this period. HCUP databases represent a stratified 20% sample of all admissions to US community hospitals, allowing for national estimates of hospitalizations. The database includes data from roughly one thousand hospitals nationwide, encompassing more than 7 million patient records annually. Rehabilitation and long-term acute care hospitals are excluded, while emergency department discharges are captured separately in the Nationwide Emergency Department Sample. Diagnoses are made and recorded by treating physicians at discharge using ICD-9 codes; however, the database does not specify the principal cause of hospitalization. Also, these codes reflect administratively documented diagnoses at hospital discharge and do not provide information on diagnostic method, surgical confirmation or the time relationships between diagnoses. The extraction of relevant variables was based on ICD-9 codes. We applied 477.x for allergic rhinitis; 617.x for endometriosis; 493.xx for asthma; 372.05 and 372.14 for allergic conjunctivitis; 642.0–642.4, 642.10–642.14, 642.20–642.24, 401.0, 401.1, 401.9 for chronic hypertension; 250.x for diabetes mellitus; 278.00, 278.01, 278.02, 278.03, 278, 278.0 for obesity; 440.x for atherosclerosis; 272.x) for dyslipidemia; 300.0x, 300.2x, 300.3x, 309.8x for anxiety disorders; 691.8 for atopic dermatitis; and 305.1 for smoking. Patients with cancer (150.x-165.x, 170.x-176.x, 179.x-184.x, 188.x, 189.x) were excluded. We combined allergic rhinitis and allergic conjunctivitis diagnoses into a single variable representing allergic rhinoconjunctivitis. We conducted the analyses using SPSS version 27 and SAS version 9.4. The prevalence of endometriosis, anxiety, allergic rhinoconjunctivitis, and asthma was assessed within the study population. Age was categorized into three groups: 18–24 years, 25–34 years, and ≥35 years. The chi-square test was used to compare the proportions of categorical variables. Multivariable logistic regression analyses were performed to assess the associations between endometriosis, anxiety, allergic rhinoconjunctivitis, and asthma. The models were adjusted for age, race, insurance type, smoking status, hypertension, obesity, diabetes mellitus, dyslipidemia, and atherosclerosis. Women without endometriosis and anxiety served as the reference group. Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. A p value of <0.05 was considered statistically significant. Given the number of comparisons and model terms examined, we predefined the primary analyses as the association between endometriosis and asthma. All additional subgroup and comorbidity analyses were considered exploratory.

Of the 12,814,970 patients hospitalized between 2007 and 2014, 1,042,015 had asthma, 50,867 had allergic rhinoconjunctivitis, 831,239 had anxiety without endometriosis, 85,990 had endometriosis without anxiety, and 8,880 had both anxiety and endometriosis. During the study period (2007–2014), the prevalence of asthma and anxiety disorders increased, whereas the prevalence of endometriosis slightly declined and allergic rhinoconjunctivitis remained relatively stable and low. Asthma rose steadily from 7.0% to 8.8%, while anxiety disorders showed a more marked increase from 3.8% to 10.4%. In contrast, the prevalence of endometriosis decreased modestly from 0.8% to 0.6% ( Fig. 1 ). The characteristics of women with asthma, allergic rhinoconjunctivitis, anxiety, and endometriosis are shown in Tables 1 and 2 . Women with allergic rhinoconjunctivitis were more likely to be older, white, and privately insured. They also had higher rates of comorbid conditions such as obesity, anxiety, and depression. Similarly, women with asthma were more often aged ≥35 years, had higher rates of Medicaid use, and showed significantly greater prevalence of comorbidities, including obesity, hypertension, and mental health disorders. Compared to those without anxiety or endometriosis, patients with anxiety (with or without endometriosis) were more likely to be older and white. These patients had higher rates of smoking, obesity, hypertension, dyslipidemia, diabetes mellitus, atherosclerosis, depression, and asthma. Similar patterns were observed among patients with endometriosis without anxiety. Table 3 presents the associations between anxiety, endometriosis, and the odds of asthma and allergic rhinoconjunctivitis among hospitalized patients aged 18–49 and 18–34 years, after adjusting for age categories, race, insurance, smoking, hypertension, obesity, diabetes mellitus, dyslipidemia, and atopic dermatitis. For patients aged 18–49 years, anxiety without endometriosis was associated with increased odds of asthma (OR 1.81, 95% CI 1.80–1.82) and allergic rhinoconjunctivitis (OR 2.02, 95% CI 1.97–2.07). Endometriosis without anxiety was also associated with asthma (OR 1.19, 95% CI 1.16–1.22) and allergic rhinoconjunctivitis (OR 1.54, 95% CI 1.41–1.68). The combination of both anxiety and endometriosis showed the highest odds of asthma (OR 2.07, 95% CI 1.94–2.20) and allergic rhinoconjunctivitis (OR 2.78, 95% CI 2.30–3.36). Among patients aged 18–34 years, the associations were even stronger: anxiety without endometriosis was associated with asthma (OR 2.20, 95% CI 2.18–2.22) and allergic rhinoconjunctivitis (OR 2.54, 95% CI 2.43–2.66). Endometriosis without anxiety showed an OR of 1.64 (95% CI 1.57–1.71) for asthma and 1.80 (95% CI 1.51–2.14) for allergic rhinoconjunctivitis. The combination of both conditions resulted in the highest odds: asthma (OR 2.57, 95% CI 2.35–2.81) and allergic rhinoconjunctivitis (OR 3.45, 95% CI 2.55–4.66). Trends in the prevalence of asthma, allergic rhinoconjunctivitis, endometriosis, and anxiety disorders among hospitalized patients from 2007 to 2014. Characteristics of women (aged 18–49 years) with and without allergic rhinoconjunctivitis and asthma Hospitalized women (age 18–49) with and without anxiety and endometriosis Adjusted associations between anxiety, endometriosis, rhinoconjunctivitis, and asthma hospitalized patients aged 18–49 and 18–34 1 Adjusted for age categories, race, insurance, smoking, hypertension, obesity, diabetes mellitus, dyslipidemia, rhinoconjunctivitis, and atopic dermatitis. 2 Adjusted for age categories, race, insurance, smoking, hypertension, obesity, diabetes mellitus, dyslipidemia, asthma, and atopic dermatitis.

Our study found a strong association between endometriosis and anxiety with allergic rhinoconjunctivitis and asthma, particularly in patients under the age of 35. The combination of endometriosis and anxiety further amplified the relationship with asthma. Also, our findings support the hypothesis that endometriosis, as a systemic inflammatory condition, may contribute to endothelial dysfunction.

This study demonstrates an increasing prevalence of ICD-coded diagnoses of anxiety and asthma over the study period, while the prevalence of endometriosis among hospitalized women declined. Moreover, both anxiety and endometriosis were associated with a higher prevalence of asthma and allergic rhinoconjunctivitis, with stronger associations among patients under the age of 35. Although the HCUP database does not provide clinical narrative or treatment details, it captures reliable prevalence data that enabled us to identify these epidemiologic associations. Figure 2 illustrates the possible relationships between endometriosis, anxiety, asthma, and allergic rhinoconjunctivitis. Associations between asthma, endometriosis, and anxiety. The observed increase in asthma prevalence in this study reflects inpatient discharge-coded data and may be influenced by changes in coding practices, comorbidity documentation, and care pathways over time rather than true population-level prevalence. However, similar upward trends in asthma prevalence have been reported in other regions, including British Columbia [ 16 ], the USA [ 17 ], and southern Brazil. In Brazil, physician-diagnosed and lifetime asthma rose by over 30%, with higher rates consistently observed among women and individuals with lower income [ 18 ]. Rising obesity, air pollution, and occupational exposures may contribute to increasing asthma prevalence in the USA, as reported in a previous study covering 2000–2009 [ 17 ]. The lasting effects of the 2008 financial crisis, job and financial stress, increased social media use, and growing social isolation, especially among young and unmarried adults were cited as possible reasons for the increase in anxiety during this period [ 19 ]. A meta-analysis [ 20 ] of 19 case-controlled studies ( n = 106,813) found significantly higher anxiety in individuals with asthma. Compared to controls, the odds were nearly doubled. Our findings align with these results, showing a strong association between anxiety and asthma, particularly among individuals aged 18–34 years (OR 2.20, 95% CI 2.18–2.22). Growing evidence suggests that inflammation is a key biological mechanism through which psychological stress exerts its effects on health [ 10 ]. Neuroimaging studies indicate that changes in brain structure and function may contribute to the link between asthma and internalizing disorders. Patients with asthma show altered connectivity in emotion-related brain regions, and increased activity in the anterior insula has been associated with greater inflammation. Stress appears to influence these processes as individuals with lower chronic stress display distinct metabolic patterns in emotion-processing areas and higher airway inflammation after stress, along with poorer asthma control and more severe anxiety and depression [ 21 ]. In our study, endometriosis was independently associated with increased odds of asthma, with a stronger association observed among younger individuals aged 18–34 years. These findings are consistent with recent meta-analytic evidence [ 22 ], which reported a significant association between asthma and endometriosis (OR 1.79, 95% CI 1.51–2.11), and further supports the biological plausibility of a link between asthma and endometriosis. Moreover, the co-occurrence of anxiety and endometriosis was associated with the highest odds of asthma, suggesting a potential synergistic effect. This highlights the importance of considering comorbid mental and gynecological conditions in the assessment and management of asthma, particularly in younger adults. Similar to our findings for allergic rhinoconjunctivitis, Yoshii et al. [ 23 ] reported that type 1 allergic diseases were linked to an increased risk of endometriosis. Endothelial function can be assessed using flow-mediated dilation (FMD) [ 24 ], which refers to the widening of an artery in response to increased blood flow. A study demonstrated that patients with asthma have reduced FMD levels compared to healthy controls [ 24 ]. Asthma is associated with increased microvascular permeability and decreased vascular reactivity [ 25 ]. Chronic rhinosinusitis is also shown to be in association with reduced FMD [ 26 ]. However, the link between allergic rhinoconjunctivitis and endothelial function is unclear, warranting further research. Endometriosis has been associated with conditions like atherosclerosis [ 6 ], Raynaud’s phenomenon [ 5 ], migraine [ 5 ], preeclampsia, and asthma which are linked to endothelial dysfunction [ 23 , 27 – 32 ] (online suppl. Fig. 1; for all online suppl. material, see https://doi.org/10.1159/000551682 ). Endothelial dysfunction contributes to smooth muscle dysfunction [ 33 ]. Inflammation, characteristic of endometriosis [ 8 ], may disrupt endothelial function and exacerbate smooth muscle dysregulation. Improved endothelial function after surgical treatment of endometriosis supports the role of endothelial dysfunction. A 2-year follow-up study showed surgical treatment of endometriosis improves endothelial function [ 34 ]. These findings suggest that endothelial dysfunction may represent a potential shared mechanism linking endometriosis and asthma. We recommend that clinicians maintain clinical awareness of potential inflammatory and psychological comorbidities when managing these conditions. Clinicians should also be aware of psychological comorbidities, such as anxiety, which appear to be more prominent among patients with endometriosis, particularly during periods of heightened societal stress [ 35 ]. The HCUP NIS databases compile data from over a thousand hospitals across the USA, covering several million patients each year. However, our study lacks key clinical details, including disease severity, reasons for admission, and specific treatments received. This limits our ability to determine whether the observed associations are coincidental, related to the admission, or whether management of one condition influenced the course of others. Additionally, since our dataset reflects prevalence rather than true incidence, these limitations may affect the interpretation of our findings. The database does not provide information on diagnostic method so surgical or clinical confirmation cannot be assumed. In addition, although endothelial dysfunction is a potential mechanism, the administrative nature of the HCUP NIS database precludes evaluation of endothelial function. Therefore, this hypothesis remains speculative and requires confirmation in studies with detailed clinical data. Given the multiple comparisons performed, there is an increased risk of type I error (false-positive findings). Therefore, results from secondary and exploratory analyses should be interpreted with caution. Future studies should clarify the temporal and causal relationships between endometriosis, anxiety, asthma, and allergic rhinoconjunctivitis. Prospective longitudinal cohorts are needed to document the sequence of disease onset and to determine whether patients with multiple co-existing conditions experience worse outcomes than those with a single condition, potentially reflecting systemic inflammatory or endothelial dysfunction. Prospective follow-up could distinguish endometriosis-related anxiety (e.g., pain or fertility driven) from generic anxiety by comparing anxiety levels in patients with effective treatment and resolution (including fertility concerns) versus those without resolution. Prospective cohort studies, including randomized controlled trials where appropriate, could assess whether targeted treatment of one condition (e.g., endometriosis or anxiety) influences the severity or control of respiratory and allergic disease, compared with standard care. Such studies would help determine whether recognizing and treating multiple co-existing pathologies improves outcomes of the primary presenting condition. These findings could inform risk stratification, support individualized management, and highlight the value of multidisciplinary collaboration between gynecology, pulmonology, allergy/immunology, and mental health specialties.

Endometriosis is a chronic, estrogen-dependent condition characterized by the ectopic presence of endometrial-like tissue outside the uterine cavity [ 1 ]. It affects approximately 196 million women in the world [ 2 ]. The clinical presentation is heterogeneous and may include chronic pelvic pain, infertility [ 3 ], and psychological comorbidities such as anxiety and depression [ 4 ]. Several studies have linked endometriosis to comorbid conditions such as Raynaud’s phenomenon [ 5 ], atherosclerosis [ 6 ], and an increased risk of venous thromboembolism at a younger age [ 7 ]. There is increasing evidence that endometriosis is a chronic inflammatory disease involving both local and systemic processes. Studies have reported elevated levels of proinflammatory mediators such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in the peritoneal fluid and blood of affected women. These immune changes may contribute to the implantation and persistence of endometrial tissue outside the uterus, although it remains uncertain whether inflammation is a cause or a result of the disease. TNF-α, in particular, has been suggested as a potential biomarker for endometriosis in peripheral blood, endometrial tissue, and menstrual effluent [ 8 , 9 ]. Anxiety is a known contributor to the onset and progression of several widespread and high-cost chronic conditions, including cardiovascular disease and chronic pain syndromes [ 10 ]. It affects an estimated 374 million individuals globally, corresponding to approximately 4,802 cases per 100,000 populations [ 11 ]. Asthma is a heterogeneous respiratory disorder affecting over 300 million individuals worldwide. It is characterized by variable airflow limitation and airway hyperresponsiveness, leading to episodic, reversible bronchoconstriction [ 11 ]. This phenomenon is typically triggered by environmental factors such as allergens, reflecting an exaggerated airway-narrowing reaction. Emerging evidence also points to inflammation-independent mechanisms in disease development. Systemic inflammation may link these disorders to asthma. It is marked by elevated inflammatory markers such as CRP, IL-6, IL-1β, TNF-α, and leptin. Increased IL-6 and CRP are associated with reduced lung function and neutrophilic airway inflammation in severe asthma [ 12 , 13 ]. TNF-α also enhances eosinophil survival [ 14 ]. Allergic rhinoconjunctivitis, triggered by an IgE-mediated immune response to allergen exposure, is frequently associated with asthma [ 15 ]. Despite growing evidence linking endometriosis, anxiety, and asthma through shared inflammatory and immunological pathways, studies exploring their interrelationship remain limited [ 12 ]. The aim of our study was to evaluate association between endometriosis, anxiety, and asthma.

Togas Tulandi was a member of the journal’s Editorial Board at the time of submission.

Access to the HCUP NIS databases was supported by the Academic Enrichment Fund of the Obstetrics and Gynecology Department of the McGill University Health Center.

Ethical approval was not required for this study in accordance with local and national regulations, as specified by the Tri-Council Policy Statement (2010). The MUHC REB Full Board waived the requirement for informed consent as the study used only anonymous, publicly available data.

H. Nassiri Kigloo designed the study, extracted and managed data from the HCUP dataset, and performed statistical analysis under the supervision of E. Suarthana. H. Nassiri Kigloo drafted the manuscript. T.C. Montreuil, E. Suarthana, and T. Tulandi provided input for the study design and critically reviewed the manuscript and analysis.