Depression, Education, and Quality of Life in Women With Endometriosis

Ria N Gajar

Depression, Education, and Quality of Life in Women With Endometriosis

Ria N Gajar

Design This cross-sectional study examined the association between depressive symptoms and physical HRQoL among U.S. women with endometriosis. Analyses followed NHANES analytic guidelines and accounted for the survey’s stratified, multistage probability sample. Variable definitions and levels of measurement are summarized in Appendix A. Data Source Data were obtained from the 2005–2006 NHANES, a nationally representative survey conducted by the Centers for Disease Control and Prevention (CDC, 2023). NHANES integrates household interviews with physical examinations conducted in mobile examination centers (MECs). This study used interview and MEC data, applying MEC examination weights (WTMEC2YR), masked variance strata, and masked primary sampling units (PSUs) to produce design-adjusted, nationally representative estimates. Participants Eligible participants were women ages 20–54 years who self-reported a physician diagnosis of endometriosis (RHQ360). This age range corresponded to NHANES skip 35 patterns for endometriosis questions and for the educational attainment (DMDEDUC2) item. Participants were included in the analytic sample if they had complete data on depressive symptoms, physically unhealthy days, and all covariates. The final analytic sample consisted of N = 4,139 unweighted cases, representing approximately 186.6 million U.S. women when weighted. Variables and Measures Independent Variable Depressive symptoms were assessed using the Patient Health Questionnaire-2 (PHQ-2), which includes two items assessing depressed mood and anhedonia. Consistent with validated screening practice, participants endorsing at least one item were classified as having depressive symptoms (PHQ-2 ≥ 1). Dependent Variable (Physical HRQoL) Physical HRQoL was operationalized using the number of physically unhealthy days in the past 30 days (HSQ470). Following NHANES HRQoL conventions and to address the variable’s skewed distribution, responses were dichotomized to reflect frequent physical distress: • 0 = ≤13 physically unhealthy days • 1 = ≥14 physically unhealthy days The ≥14-day threshold is widely used in population studies as a marker of frequent physical distress (Centers for Disease Control and Prevention [CDC], 2000). 36 Covariates Models adjusted for demographic and socioeconomic factors commonly associated with HRQoL, including: • Age at screening (RIDAGEYR; continuous) • Family income-to-poverty ratio (INDFMPIR; continuous) • Education level (DMDEDUC2; categorical) • Marital status (DMDMARTL; categorical, collapsed to marital3 for analysis) • Household size (DMDHHSIZ; continuous) All covariates were coded using NHANES-standard categories and values to ensure consistency with prior NHANES-based studies. Measurement Rationale The PHQ-2 is a brief, validated screener with strong psychometric properties in population-based samples and good sensitivity for identifying depressive symptoms (Kroenke et al., 2003; Löwe et al., 2010). The ≥14-day threshold for physically unhealthy days is an established indicator of frequent physical distress and facilitates interpretation of logistic regression models in complex survey data (CDC, 2000). Dichotomizing HRQoL variables is consistent with prior NHANES analyses and helps address non- normal distributions (Kemp et al., 2024). Use of MEC examination weights, masked variance strata, and PSUs ensured that estimates were nationally representative and accounted for NHANES’s multistage sampling design, in accordance with CDC recommendations. 37 Data Analysis All analyses were conducted in SPSS Version 29 using the Complex Samples module to account for NHANES’ multistage, stratified probability sampling design. MEC examination weights (WTMEC2YR), masked variance strata (SDMVSTRA), and primary sampling units (SDMVPSU) were applied so that estimates reflected nationally representative inference rather than simple random sampling. A complete-case analytic approach was used for all models. Weighted descriptive statistics (proportions, means, and 95% confidence intervals) were used to characterize the analytic sample. A complex samples logistic regression model estimated the association between depressive symptoms and a dichotomous indicator of physically unhealthy days in the past 30 days (≤13 vs. ≥14 days; phys_unhealthy14). Depressive symptoms (PHQ-2 ≥ 1) served as the primary independent variable. Covariates selected a priori for epidemiologic relevance included age, family income-to-poverty ratio (PIR), education level, marital status, and household size. Model significance and individual parameters were evaluated using design- adjusted Wald F-statistics with α = .05, and results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Model validity was assessed through review of SPSS output for warnings, examination of multicollinearity, evaluation of design effects, and consideration of design-based degrees of freedom. 38 Missing Data A complete-case approach was used, consistent with NHANES analytic guidance, to preserve the integrity of sampling weights and variance estimation in the stratified, multistage design (Kemp et al., 2024). Participants missing data on depressive symptoms, physically unhealthy days, or covariates were excluded from the analytic sample. Multiple imputation was not used because of methodological challenges associated with integrating imputation procedures into complex survey designs.

Results

Sample Characteristics The analytic sample included N = 4,139 unweighted cases, representing an estimated 186.6 million women in the U.S. civilian, non-institutionalized population. The mean age was 46.25 years (SE = 0.78). The average family income-to-poverty ratio (PIR) was 3.13 (SE = 0.08), indicating that participants lived at just over three times the federal poverty threshold. Most women had at least some college education, and the mean household size was 2.92 persons. Approximately 27.6% of women screened positive for depressive symptoms (PHQ-2 ≥ 1). With respect to physical HRQoL, about 9.7% of women reported ≥14 physically unhealthy days in the past 30 days, whereas 90.3% reported ≤13 physically unhealthy days. Weighted sample characteristics are summarized in Table 1. NHANES sampling weights generate population-level estimates; however, these values should be interpreted as representations rather than literal population counts. 39 Table 1 Sample Characteristics of U.S. Women With Endometriosis (Physical HRQoL Analysis, NHANES 2005–2006) Variable Weighted value SE / % Continuous variables Age (years) 46.25 SE = 0.78 Family income-to-poverty ratio (PIR) 3.13 SE = 0.08 Household size (persons) 2.92 — Mental health indicator PHQ-2 ≥ 1 (depressive symptoms) 27.6% — Physically unhealthy days (past 30 days) ≤13 physically unhealthy days 90.3% — ≥14 physically unhealthy days 9.7% — Education level (DMDEDUC2) Less than high school 5.9% — High school graduate 10.9% — Some college 24.8% — Associate degree 31.7% — College graduate or higher 26.7% — Marital status (marital3) Married/partnered 66.9% — Previously married 18.6% — Never married 14.5% — Note. Weighted estimates reflect the NHANES 2005–2006 complex multistage survey design using MEC examination weights (WTMEC2YR). Unweighted N = 4,139. Weighted estimates represent the U.S. civilian, non-institutionalized population of women with endometriosis and should be interpreted as population-level representations rather than literal population counts. Physically unhealthy days refer to the number of days in the past 30 days during which physical health was reported as not good. Association Between Depressive Symptoms and Physically Unhealthy Days A complex samples logistic regression model was conducted to examine the association between depressive symptoms and physical health–related quality of life, 40 operationalized as reporting ≥14 physically unhealthy days in the past 30 days, adjusting for age, family income-to-poverty ratio (PIR), education, marital status, and household size. The overall model was statistically significant, Wald F(10, 6) = 32.07, p < .001, and demonstrated modest explanatory power (Nagelkerke R² = .154). Women who screened positive for depressive symptoms had 78% lower odds of reporting ≤13 physically unhealthy days (OR = 0.22, 95% CI [0.16, 0.32], p < .001), indicating worse physical HRQoL. Age and family income-to-poverty ratio (PIR) were also significant predictors. Each additional year of age was associated with a 2% decrease in the odds of reporting ≤13 physically unhealthy days (OR = 0.98, 95% CI [0.97, 0.99], p < .001). In contrast, each unit increase in PIR was associated with a 13% increase in the odds of reporting ≤13 physically unhealthy days (OR = 1.13, 95% CI [1.05, 1.21], p = .002), indicating better physical HRQoL. Education showed a borderline omnibus association (Wald F(4, 12) = 3.21, p = .052). Compared with college graduates, women with less than a high school education had 40% lower odds of reporting ≤13 physically unhealthy days (OR = 0.60, 95% CI [0.39, 0.91]), and women with an associate degree had 41% lower odds (OR = 0.59, 95% CI [0.38, 0.93]). Marital status was not significantly associated with physically unhealthy days (Wald F(2, 14) = 0.21, p = .817). Household size was also not significantly associated, with each additional household member associated with a 6% increase in the odds of reporting ≤13 physically unhealthy days (OR = 1.06, 95% CI [0.92, 1.23], p = .398). 41 Table 2 Complex Samples Logistic Regression Predicting ≥14 Physically Unhealthy Days Among U.S. Women With Endometriosis (NHANES 2005–2006) Predictor Wald F df1 df2 p OR (ExpB) 95% CI for OR Depressive symptoms (PHQ-2 ≥1) 84.36 1 15 < .001 0.22 0.16–0.32 Age (years) 27.49 1 15 < .001 0.98 0.97–0.99 Family income-to-poverty ratio (PIR) 13.31 1 15 .002 1.13 1.05–1.21 Education level (DMDEDUC2)ᵃ 3.21 4 12 .052 — — • Less than HS vs College+ — — — — 0.60 0.39–0.91 • HS vs College+ — — — — 0.85 0.49–1.46 • Some college vs College+ — — — — 0.69 0.43–1.12 • AA/Associate vs College+ — — — — 0.59 0.38–0.93 Marital status (marital3)ᵇ 0.21 2 14 .817 — — • Married/partnered vs Never married — — — — 1.08 0.69–1.71 • Previously married vs Never married — — — — 0.94 0.55–1.61 Household size 0.76 1 15 .398 1.06 0.92–1.23 Model fit: Wald F(10, 6) = 32.07, p < .001; Pseudo-R²: Cox & Snell = .072; Nagelkerke = .154; McFadden = .118; Weighted N: ≈ 186.6 million U.S. women Note. Reference groups: education = college graduate+; marital status = never married; depressive symptoms = no symptoms. The logistic model was parameterized for the odds of reporting ≤13 physically unhealthy days; therefore, odds ratios < 1 indicate higher odds of reporting ≥14 physically unhealthy days (i.e., worse physical HRQoL). ᵃ Education omnibus test used Exp(B) contrasts to illustrate directional patterns. ᵇ Marital status omnibus test was not significant (p = .817). Bold indicates p < .05. 42

Discussion

The purpose of this study was to examine the association between depressive symptoms and physical health–related quality of life (HRQoL) among U.S. women with endometriosis using nationally representative NHANES 2005–2006 data. Physical HRQoL was operationalized as reporting ≥14 physically unhealthy days in the past 30 days, a marker of substantial and frequent physical distress. Findings from the complex samples logistic regression model indicated that depressive symptoms were strongly and independently associated with poor physical HRQoL, even after adjusting for age, family income-to-poverty ratio (PIR), education, marital status, and household size. Women who screened positive for depressive symptoms had 78% lower odds of reporting ≤13 physically unhealthy days (OR = 0.22, 95% CI [0.16, 0.32], p < .001), corresponding to markedly higher odds of reporting ≥14 physically unhealthy days, a marker of worse physical HRQoL. This magnitude of association is clinically meaningful and aligns with existing research demonstrating that depression is closely linked to greater somatic symptom burden, heightened pain perception, and functional limitations among individuals with chronic health conditions, including endometriosis (Cofini et al., 2024; Rees et al., 2022). Within the context of endometriosis—where pelvic pain, fatigue, and reduced physical functioning are already common—depressive symptoms may intensify the reported severity and frequency of physically unhealthy days. Consistent with Engel’s biopsychosocial model, the findings indicate the importance of social and structural determinants in physical health–related quality of life. Each additional year of age was associated with a 2% increase in the odds of frequent 43 physically unhealthy days, and lower family income-to-poverty ratio (PIR) was associated with higher odds of frequent physically unhealthy days. These patterns are consistent with the role of life-course processes and socioeconomic constraints in physical health outcomes among women with endometriosis. Education and household size were not statistically significant predictors, and marital status demonstrated a complex pattern that may reflect heterogeneity in the quality and nature of intimate relationships and household roles. These results indicate that global indicators such as marital status and household size may not fully capture dimensions of social support, caregiving, and role strain in this population. Although the model explained a modest proportion of variance (Nagelkerke R² = .154), the direction and magnitude of the associations are theoretically coherent and consistent with prior literature on depression and HRQoL. At the same time, interpretation should be tempered by the relatively low prevalence of ≥14 physically unhealthy days (about 10%), which may limit precision for some categorical contrasts and contribute to modest overall model fit. Taken together, these considerations indicate that the observed associations likely reflect underlying relationships but should be interpreted as conservative, preliminary estimates pending replication with larger samples, alternative model specifications, or pooled NHANES cycles. Interpretation of Results Taken together, the results indicate that depressive symptoms are an important correlate of physical HRQoL among women with endometriosis at the population level. The odds ratio of 0.22 indicates that women with depressive symptoms had 78% lower 44 odds of reporting ≤13 physically unhealthy days, corresponding to higher odds of crossing a clinically meaningful threshold of frequent physical distress (≥14 physically unhealthy days). The significant associations between age, PIR, and the outcome further support a biopsychosocial interpretation of the findings. Older women may face cumulative health challenges, comorbid conditions, or longer durations of endometriosis symptoms, all of which may contribute to more frequent physically unhealthy days. Lower PIR likely reflects limited access to high-quality care, delayed diagnosis, barriers to specialized endometriosis treatment, and greater day-to-day stressors, which together may exacerbate both symptom burden and the experience of physical distress (Sommer et al., 2024). The non-significant associations for education and household size suggest that not all sociodemographic indicators function in the same way for physical HRQoL in this population. Education may exert more influence on health literacy, advocacy, or long- term disease management than on the frequency of physically unhealthy days captured over a 30-day period. Similarly, household size may not differentiate between supportive, neutral, or stressful household environments. Future work that incorporates direct measures of social support, caregiving responsibilities, and relationship quality may provide a more precise understanding of how the social environment shapes physical HRQoL for women with endometriosis. Overall, the findings support Engel’s biopsychosocial model by demonstrating that depressive symptoms (psychological), age and cumulative health burden (biological), and PIR (social) jointly contribute to physical HRQoL among women with 45 endometriosis. The study adds population-based evidence to a literature that has largely relied on clinic-based samples and underscores the importance of integrating mental health and selected social factors into models of endometriosis care and research.

Limitations

Several limitations should be considered when interpreting these findings. First, the cross-sectional design precludes causal inference. It is not possible to determine whether depressive symptoms lead to more physically unhealthy days, whether frequent physical distress contributes to the development or persistence of depressive symptoms, or whether the relationship is bidirectional. Longitudinal studies are needed to clarify temporal ordering. Second, all key measures—including depressive symptoms, physically unhealthy days, and endometriosis diagnosis—were based on self-report. Self-report may be subject to recall bias, underreporting, or overreporting. Self-reported endometriosis may also reflect differential access to gynecologic evaluation and diagnostic services, which could introduce selection bias related to socioeconomic status or healthcare access. Third, the analysis relied on a complete-case approach, which may introduce bias if participants with missing data differ systematically from those with complete data. Although complete-case analysis is consistent with NHANES analytic guidance and preserves the integrity of complex survey weighting, it may underestimate variability or exclude participants with more severe disease or greater social vulnerability (Kemp et al., 2024). 46 Fourth, because only about 1 in 10 women reported ≥14 physically unhealthy days, some combinations of predictors were relatively sparse, which may reduce the precision of estimates for certain categories. This is reflected in modest model fit indices and wide confidence intervals for some parameters. Fifth, the analysis was restricted to one NHANES cycle (2005–2006) and to U.S. women ages 20–54 years, which may limit generalizability to other age groups, time periods, or countries with different healthcare systems and social contexts. Additionally, NHANES discontinued the endometriosis diagnostic item (RHQ360) after 2005–2006, preventing replication of physical HRQoL analyses using more recent cycles and limiting the ability to examine long-term trends. Implications Despite these limitations, the findings have important implications for clinical practice and public health. The strong association between depressive symptoms and frequent physically unhealthy days suggests that mental health assessment should be a routine component of endometriosis care. Incorporating brief depression screening tools, such as the PHQ-2 or PHQ-9, into gynecologic and primary care encounters could facilitate early identification of women who may benefit from further evaluation, counseling, or treatment for depression. The results also highlight the need for integrated, multidisciplinary care models that address both the physical and psychological dimensions of endometriosis. Collaborative care approaches that include gynecologists, primary care clinicians, pain 47 specialists, mental health providers, and social workers may be particularly well suited to address the interconnected biopsychosocial drivers of physical HRQoL in this population. From a public health perspective, the protective association of higher PIR suggests that strategies to improve access to high-quality, comprehensive care for women with lower income may help mitigate the physical health burden of endometriosis. Policies that reduce financial barriers to specialty care, mental health services, and pain management, as well as efforts to improve diagnostic timeliness and patient education, may support more equitable outcomes. The findings further support the use of HRQoL indicators, such as physically unhealthy days, as surveillance measures to monitor the burden of endometriosis and evaluate the impact of policy and programmatic interventions. Recommendations for Future Research Future research should prioritize longitudinal designs to clarify the temporal relationships among depressive symptoms, physically unhealthy days, and other endometriosis-related outcomes. Prospective studies could determine whether changes in depressive symptoms predict subsequent changes in physical HRQoL or whether integrated interventions targeting depression lead to measurable improvements in physical functioning. More nuanced measurement of social determinants and interpersonal contexts is also warranted. Including variables such as social support, caregiving burden, discrimination, employment conditions, and health insurance coverage may provide a more comprehensive understanding of how social environments shape physical HRQoL 48 in this population. Testing potential moderators—such as income, social support, race and ethnicity, symptom severity, and access to specialty care—may also clarify which subgroups are most vulnerable to poor physical HRQoL and for whom interventions may be most effective. Methodologically, future studies may benefit from pooling multiple NHANES cycles to increase sample size, reduce sparse data issues, and improve the stability of complex survey regression estimates. Where feasible, the use of alternative modeling strategies that accommodate rare outcomes or separation (e.g., penalized regression methods) may further strengthen inference. Finally, intervention studies that evaluate integrated, biopsychosocial approaches to endometriosis care could help translate the present findings into practical strategies for reducing both depressive symptoms and physical health burden.

Conclusion

In summary, I found that depressive symptoms were strongly associated with poor physical health–related quality of life among U.S. women with endometriosis, as reflected by frequent physically unhealthy days. Even after adjusting for age, socioeconomic status, education, marital status, and household size, women with depressive symptoms had markedly higher odds of reporting ≥14 physically unhealthy days, corresponding to a 78% reduction in the odds of reporting ≤13 physically unhealthy days. Older age and lower PIR further contributed to elevated physical health burden, underscoring the interconnected biological, psychological, and social influences highlighted in the biopsychosocial framework. 49 These findings emphasize the importance of integrating depression screening, psychosocial assessment, and supportive care into the routine management of endometriosis. Although methodological limitations and modest model fit temper interpretation, the results provide meaningful, population-based evidence that depressive symptoms are a central component of the physical health experience for women living with endometriosis. This work strengthens our knowledge of how psychological and social factors shape physical HRQoL and reinforces the need for holistic, multidisciplinary approaches to care. 50

References

Abstract

Endometriosis is a chronic gynecologic condition associated with substantial psychological burden. Although depressive symptoms are known to affect mental health– related quality of life (HRQoL), it remains unclear whether educational attainment modifies this relationship. Guided by Engel’s biopsychosocial model, this cross-sectional study used 2005–2006 National Health and Nutrition Examination Survey (NHANES) data to examine whether education moderated the association between depressive symptoms and mental HRQoL, operationalized as frequent mentally unhealthy days, among U.S. women with endometriosis. The analytic sample included N = 4,131 unweighted cases, representing approximately 186.4 million women when weighted. Complex samples logistic regression estimated a main-effects model and a moderation model including a depression-by-education interaction term. Women with depressive symptoms had approximately 829% higher odds (about nine times the odds) of reporting ≥14 mentally unhealthy days compared with women without depressive symptoms (main-effects OR = 9.29, 95% CI [7.63, 11.31], p < .001). This association remained strong in the moderation model, with depressive symptoms associated with approximately 661% higher odds (about seven times the odds) of frequent mentally unhealthy days (OR = 7.61, 95% CI [4.42, 13.10], p < .001). Educational attainment did not significantly moderate this association (interaction OR = 0.94, 95% CI [0.80, 1.11], p = .462). Overall, the findings indicate that depressive symptoms are strongly associated with poor mental HRQoL among women with endometriosis across educational levels, 56 underscoring the importance of routine depression screening and accessible mental health care.

Introduction

The psychological toll of endometriosis extends beyond physical pain, contributing to chronic stress, social isolation, and diminished emotional well-being (Della Corte et al., 2020). Women living with endometriosis often experience elevated rates of depression, which can interfere with coping mechanisms, social engagement, and treatment adherence (Cofini et al., 2024; Rees et al., 2022). Depressive symptoms may exacerbate cognitive and emotional burden, intensifying perceptions of distress and impairing mental health–related quality of life (HRQoL). Educational attainment may function as a social resource that shapes resilience and access to care. Higher education has been linked to greater health literacy, problem- solving ability, and psychological coping skills—factors that may mitigate the impact of depressive symptoms on mental HRQoL (Sommer et al., 2024). At the same time, educational gradients in health are complex and may interact with other structural forces, such as income, employment conditions, and access to mental health services. Guided by Engel’s (1977) biopsychosocial model, which is applied to conceptualize health as influenced by the interplay of biological, psychological, and social factors, I examined whether educational attainment moderated the association between depressive symptoms and mental HRQoL among U.S. women with endometriosis, using data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). By focusing on education as a potential buffer within a 57 population-based framework, I assessed whether higher education attenuated the association between depressive symptoms and frequent mentally unhealthy days. Understanding these patterns may inform targeted screening strategies and more equitable, patient-centered approaches to mental health support for women affected by endometriosis. Research Questions The primary research question guiding this study was: To what extent did educational attainment moderate the association between depressive symptoms and mental health–related quality of life (HRQoL) among women diagnosed with endometriosis? To address this overarching question, the study examined the following subquestions: • What was the association between depressive symptoms and reporting ≥14 mentally unhealthy days in the past 30 days? • What was the association between depressive symptoms and ≥14 mentally unhealthy days after accounting for educational attainment and age? • Did educational attainment moderate the association between depressive symptoms and ≥14 mentally unhealthy days? All hypotheses were evaluated using two-tailed analyses without assuming directionality.

Methods

Design A cross-sectional design was used to examine whether educational attainment moderated the association between depressive symptoms and mental health–related 58 quality of life among U.S. women with endometriosis. Analyses leveraged data from the 2005–2006 NHANES cycle and followed complex survey analytic guidelines. Variables, labels, and levels of measurement are summarized in Appendix A. Data Source Data were drawn from the 2005–2006 National Health and Nutrition Examination Survey (NHANES), a stratified, multistage probability survey of the U.S. civilian, noninstitutionalized population conducted by the Centers for Disease Control and Prevention (CDC, 2023). NHANES combines standardized interviews with physical examinations and laboratory assessments conducted in mobile examination centers (MECs). I used interview and MEC data and applied MEC examination weights (WTMEC2YR), masked variance strata, and masked primary sampling units (PSUs) to obtain nationally representative, design-adjusted estimates. A Data Availability Statement will be included in accordance with journal requirements. Participants Eligible participants were women ages 20–54 years who self-reported a physician diagnosis of endometriosis (RHQ360). The lower age cutoff aligned with NHANES’s education measure, which is collected only for adults ages 20 years and older, and the upper cutoff corresponded to NHANES skip patterns for endometriosis questions. Participants were included in the analytic sample if they had complete data on depressive symptoms, mentally unhealthy days, educational attainment, and age. The final analytic sample for the moderation models consisted of N = 4,131 unweighted cases, representing approximately 186.4 million women when weighted. 59 Variables and Measures Independent Variable (Depressive Symptoms) Depressive symptoms were assessed using the Patient Health Questionnaire-2 (PHQ-2), which includes two items reflecting anhedonia and depressed mood. Consistent with validated screening practice, participants endorsing at least one item were classified as having depressive symptoms (PHQ-2 ≥ 1), and those with no endorsements were classified as not having depressive symptoms. Moderator (Educational Attainment) Educational attainment (DMDEDUC2) was categorized into five levels consistent with NHANES coding for adults ages 20 years and older: • Less than 9th grade • 9th–11th grade (including 12th grade with no diploma) • High school graduate/GED or equivalent • Some college or associate degree • College graduate or above For moderation analyses, education was modeled as a categorical predictor with college graduate or higher serving as the reference category. Dependent Variable (Mental HRQoL) Mental HRQoL was operationalized using the number of mentally unhealthy days in the past 30 days (HSQ480). Responses ranged from 0 to 30 days and were dichotomized to indicate frequent mental distress: • 0 = <14 mentally unhealthy days 60 • 1 = ≥14 mentally unhealthy days The ≥14-day threshold is widely used in public health surveillance as an indicator of frequent mental distress (Centers for Disease Control and Prevention CDC, 2000). Covariate Age at screening (RIDAGEYR) was included as a continuous covariate to account for potential age-related differences in mental HRQoL. Measurement Rationale The PHQ-2 has been validated as a brief, reliable measure of depressive symptoms in epidemiologic research and demonstrates good sensitivity for identifying individuals at risk for depression (Kroenke et al., 2003; Löwe et al., 2010). The ≥14-day threshold for mentally unhealthy days aligns with established public health definitions of frequent mental distress and facilitates interpretation of logistic regression models in complex survey data (CDC, 2000). Dichotomizing HRQoL variables is consistent with prior NHANES analyses and helps address skewed distributions and sparse counts at extreme values (Kemp et al., 2024). Use of MEC examination weights, masked variance strata, and PSUs ensured that estimates were nationally representative and accounted for NHANES’s multistage sampling design, consistent with CDC recommendations. Data Analysis Three stages of analysis were conducted. First, weighted descriptive statistics (proportions, means, and 95% confidence intervals) were used to characterize the sample overall and by depressive symptom status and education level. Next, a main-effects complex samples logistic regression model (Model 1A) was estimated with frequent 61 mentally unhealthy days as the dependent variable and depressive symptoms (PHQ-2 ≥ 1) as the primary predictor, adjusting for education level, age, marital status, family income- to-poverty ratio (PIR), and household size. Finally, a moderation model (Model 1B) was estimated by adding a depression-by-education interaction term (depXeduc) to test whether the association between depressive symptoms and frequent mentally unhealthy days varied across education levels. Model significance and individual predictors were evaluated using design-adjusted Wald F statistics with α = .05, and results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Pseudo-R² values (Cox & Snell, Nagelkerke, McFadden) were used to assess explanatory power. Missing Data A complete-case analysis was employed, consistent with NHANES recommendations to preserve survey design integrity and weighting (Kemp et al., 2024). Participants missing data on depressive symptoms, mentally unhealthy days, education, or age were excluded from the regression models. Multiple imputation was not used due to methodological challenges associated with integrating imputation procedures into stratified, weighted survey designs. The potential for bias from complete-case analysis is addressed in the Limitations section.

Results

Sample Characteristics The analytic sample for the moderation models included N = 4,131 unweighted cases, representing an estimated 186.4 million women in the U.S. civilian, non- institutionalized population. The mean age was 46.22 years. The average family income- 62 to-poverty ratio (PIR) was 3.13, and the mean household size was 2.92 persons. Approximately 27.6% of women screened positive for depressive symptoms (PHQ-2 ≥ 1), while 72.4% did not. With respect to mental HRQoL, 38.1% of women were classified in the higher mentally unhealthy days group, and 61.9% were in the lower group. Most women had at least a high school education: 5.9% had less than 9th-grade education, 10.9% had 9th–11th grade, 24.8% were high school graduates or GED equivalent, 31.7% had some college or an associate degree, and 26.7% were college graduates or higher. Approximately two-thirds were married or partnered (66.9%), 18.6% were previously married, and 14.5% had never married. Weighted sample characteristics are presented in Table 1. NHANES sampling weights generate population-level estimates, which should be interpreted as representations rather than literal population counts. 63 Table 1 Sample Characteristics of U.S. Women With Endometriosis (Mental HRQoL Analysis, NHANES 2005–2006) Variable Weighted Value SE / % Continuous variables Age (years) 46.22 SE = 0.78 Family income-to-poverty ratio (PIR) 3.13 SE = 0.08 Household size (persons) 2.92 — Mental health indicators PHQ-2 ≥ 1 (depressive symptoms) 27.6% — <14 mentally unhealthy days 61.9% — ≥14 mentally unhealthy days 38.1% — Education level (DMDEDUC2) Less than 9th grade 5.9% — 9th–11th grade 10.9% — High school graduate/GED 24.8% — Some college/associate degree 31.7% — College graduate or higher 26.7% — Marital status (marital3) Married/partnered 66.9% — Previously married 18.6% — Never married 14.5% — Note. Weighted estimates reflect the NHANES 2005–2006 complex survey design using MEC examination weights (WTMEC2YR). Unweighted N = 4,131. Weighted estimates represent the U.S. civilian, non-institutionalized population of women with endometriosis and should be interpreted as population-level representations rather than literal population counts. Mentally unhealthy days refer to the number of days in the past 30 days during which mental health was reported as not good. 64 Association Between Depressive Symptoms, Education, and Mentally Unhealthy Days (Model 1A) Model 1A examined the association between depressive symptoms and frequent mentally unhealthy days, adjusting for education, age, marital status, PIR, and household size. The overall model was statistically significant, Wald F(10, 6) = 481.39, p < .001, and demonstrated good explanatory value (Nagelkerke R² = .282). Women who screened positive for depressive symptoms had approximately 829% higher odds (about nine times the odds) of reporting frequent mentally unhealthy days compared with women without depressive symptoms in the main-effects model (OR = 9.29, 95% CI [7.63, 11.31], p < .001). Education level showed a significant overall association with mentally unhealthy days, Wald F(4, 12) = 3.78, p = .033. Compared with women with a college degree or higher, those with less than a high school education had 87% higher odds of reporting frequent mentally unhealthy days (OR = 1.87, 95% CI [1.08, 3.24]), and those with a high school diploma had 40% higher odds (OR = 1.40, 95% CI [1.04, 1.89]). Odds ratios for women with some college or an associate degree did not differ significantly from those for college graduates. Age was also a significant predictor. Each additional year of age was associated with a 2% increase in the odds of reporting frequent mentally unhealthy days (OR = 1.02 per year, 95% CI [1.02, 1.03], p < .001). PIR, marital status, and household size were not significantly associated with mentally unhealthy days in this model. 65 Moderation by Educational Attainment (Model 1B) Model 1B added a depression-by-education interaction term to test whether the association between depressive symptoms and frequent mentally unhealthy days varied across education levels. The overall model remained statistically significant, Wald F(11, 5) = 1,210.46, p < .001, with similar explanatory power (Nagelkerke R² = .282). Depressive symptoms continued to show a strong and independent association with frequent mentally unhealthy days. After accounting for education, age, marital status, PIR, household size, and the interaction term, women with depressive symptoms had approximately 661% higher odds (about seven times the odds) of reporting frequent mentally unhealthy days compared with women without depressive symptoms (OR = 7.61, 95% CI [4.42, 13.10], p < .001). Age remained a significant predictor, with each additional year associated with a 2% increase in the odds of frequent mentally unhealthy days (OR = 1.02 per year, 95% CI [1.02, 1.03], p < .001). In contrast, PIR, marital status, and household size were not significantly associated with the outcome. Educational attainment demonstrated a modest overall association with mentally unhealthy days (Wald F(4, 12) = 2.50, p = .098), but none of the individual education categories differed significantly from college graduates in the presence of the interaction term. Critically, the depression-by-education interaction was not significant, Wald F(1, 15) = 0.57, p = .462 (OR = 0.94, 95% CI [0.80, 1.11]). This indicates that the strength of the association between depressive symptoms and frequent mentally unhealthy days did not differ meaningfully by education level; depressive symptoms were strongly associated with poor mental HRQoL across educational strata. 66 Table 2 Complex Samples Logistic Regression Predicting ≥14 Mentally Unhealthy Days With Depression × Education Interaction (Model 1B), NHANES 2005–2006 Predictor Wald F p OR 95% CI for OR Depressive symptoms (PHQ-2 ≥ 1) 63.43 < .001 7.61 [4.42, 13.10] Education level (DMDEDUC2)ᵃ 2.50 .098 — — Less than 9th vs. College+ — — 1.71 [0.83, 3.51] 9th–11th vs. College+ — — 1.33 [0.88, 2.01] High school/GED vs. College+ — — 0.94 [0.66, 1.32] Some college/AA vs. College+ — — 0.87 [0.65, 1.17] Age at screening (RIDAGEYR) 48.05 < .001 1.02 [1.02, 1.03] Family income-to-poverty ratio (PIR) 0.02 .888 1.00 [0.93, 1.06] Household size (DMDHHSIZ) 1.00 .333 1.03 [0.96, 1.11] Marital status (marital3)ᵇ 1.46 .266 — — Married/partnered vs. Never married — — 0.89 [0.68, 1.16] Previously married vs. Never married — — 0.76 [0.55, 1.06] Depression × Education (depXeduc) 0.57 .462 0.94 [0.80, 1.11] Note. Weighted estimates were calculated using NHANES MEC examination weights (WTMEC2YR), masked variance strata (SDMVSTRA), and masked primary sampling units (SDMVPSU). The dependent variable was reporting ≥14 mentally unhealthy days in the past 30 days (reference = <14 days). Reference groups: no depressive symptoms, college graduate or higher, and never married. Odds ratios (ORs) < 1 indicate lower odds of reporting ≥14 mentally unhealthy days (i.e., less frequent mental distress). a. Education omnibus test reflects overall group differences; contrasts demonstrate directional patterns. b. Marital status omnibus test was not statistically significant.

Discussion

I examined whether educational attainment moderated the association between depressive symptoms and mental health–related quality of life among U.S. women with 67 endometriosis using nationally representative NHANES 2005–2006 data. Mental HRQoL was operationalized as frequent mental distress (≥14 mentally unhealthy days). Across all models, depressive symptoms emerged as a consistent and powerful predictor of poor mental HRQoL, whereas educational attainment, although associated with mentally unhealthy days in some models, did not meaningfully alter the strength of the depression– HRQoL relationship. In the unadjusted and adjusted models, women who screened positive for depressive symptoms had substantially higher odds of reporting ≥14 mentally unhealthy days than women without depressive symptoms. This strong association persisted after accounting for education and age, reinforcing depressive symptoms as a central correlate of mental HRQoL in this population. These findings align with previous research documenting high psychological burden among women with endometriosis and highlight the importance of addressing depressive symptomatology in clinical and public health contexts. Educational attainment showed a significant overall association with mentally unhealthy days in the main-effects model, with women in intermediate education categories (high school and some college/associate degree) demonstrating higher odds of frequent mental distress. However, women with a college degree or higher did not differ significantly from the lowest education group. These nonlinear patterns are consistent with heterogeneity in life stressors, employment conditions, or coping resources across education strata, but numerical instability—indicated by SPSS warnings of quasi- complete separation—may also contribute to these results. 68 Critically, the depression-by-education interaction was not statistically significant. The magnitude of the association between depressive symptoms and frequent mentally unhealthy days was similar across all education levels, indicating that education did not buffer or amplify the impact of depressive symptoms on mental HRQoL. Within a biopsychosocial framework, this pattern underscores that while social factors shape overall mental health burden, depressive symptoms themselves exert the most direct and consistent influence on mental HRQoL among women with endometriosis. Interpretation of Results Taken together, the results indicate the following: Depressive Symptoms Are a Dominant Predictor of Mental HRQoL Odds ratios remained large and statistically robust across all models, demonstrating that depressive symptoms substantially increase the likelihood of frequent mentally unhealthy days, independent of education and age. This pattern highlights depressive symptoms as a key driver of mental distress in this population. Education Influences Mental HRQoL But Does Not Moderate the Depression– HRQoL Relationship Although education was associated with mentally unhealthy days overall, the interaction term was nonsignificant, with an odds ratio near 1.00. This indicates that the adverse mental health impact of depressive symptoms is relatively uniform across education levels. Higher educational attainment did not meaningfully reduce the association between depressive symptoms and frequent mentally unhealthy days. 69 Age Was a Modest But Statistically Significant Predictor of Mental HRQoL Although the magnitude of the effect was small, each additional year of age was associated with a 2% increase in the odds of frequent mentally unhealthy days, indicating a gradual accumulation of mental health burden across the adult life course. Within Engel’s biopsychosocial model, these findings reinforce the importance of addressing psychological contributors to HRQoL, particularly depressive symptoms, across all educational strata. While educational attainment shapes broader social and structural conditions, it did not modify the strong, direct association between depressive symptoms and frequent mental distress. This suggests that efforts to improve mental HRQoL in women with endometriosis should prioritize depression screening, timely mental health referral, and integrated approaches that attend to both psychological and social needs.

Limitations

Several limitations should be considered when interpreting these findings. First, the cross-sectional design precludes causal inference. It is not possible to determine whether depressive symptoms lead to increased mentally unhealthy days, whether frequent mental distress contributes to depressive symptoms, or whether the relationship is bidirectional. Second, key variables—including depressive symptoms, mentally unhealthy days, educational attainment, and endometriosis diagnosis—were self-reported and therefore subject to recall error, reporting biases, and potential misclassification. Self-reported 70 endometriosis, in particular, may reflect differential access to gynecologic evaluation and diagnostic services, which could vary by socioeconomic status and healthcare access. Third, this study used complete-case analysis, consistent with NHANES analytic guidance and recent methodological recommendations. Although appropriate for weighted survey data, complete-case analysis may introduce bias if excluded participants differ systematically from those with complete data. Fourth, SPSS issued warnings indicating quasi-complete separation and instability in the design-based covariance matrix. These numerical issues likely reflect the relatively low prevalence of ≥14 mentally unhealthy days and sparse data within some education categories. Such instability may affect the precision of parameter estimates, particularly for education contrasts and interaction terms. Finally, analyses were restricted to the 2005–2006 NHANES cycle and to women ages 20–54 years with self-reported endometriosis. As a result, generalizability to adolescents, older adults, or women in more contemporary healthcare contexts is limited. NHANES discontinued the endometriosis item after 2006, preventing replication using more recent cycles. Implications The findings have several implications for clinical practice and public health. Because depressive symptoms were consistently associated with frequent mentally unhealthy days, routine depression screening should be integrated into endometriosis care regardless of a patient’s educational background. Brief, validated tools such as the PHQ-2 71 or PHQ-9 could support early identification of women who may benefit from mental health assessment or treatment. The absence of a moderating effect of education suggests that higher educational attainment does not meaningfully protect against the mental health consequences of depressive symptoms. As a result, equitable access to mental health services—including counseling, psychotherapy, and medication management when indicated—is critical across all educational strata. Clinicians should remain attentive to depressive symptoms even among patients who appear to have strong social or educational resources. From a public health perspective, the results support integrated biopsychosocial approaches that address both psychological and social dimensions of endometriosis. Care models that combine gynecology, primary care, behavioral health, and social support may more effectively address the complex needs of women with endometriosis. Policies that reduce barriers to mental health care and promote mental health literacy could also enhance quality of life in this population. Recommendations for Future Research Future research should use longitudinal designs to clarify the temporal relationship between depressive symptoms and frequent mentally unhealthy days. Prospective studies could determine whether reductions in depressive symptoms lead to improvements in mental health–related quality of life or whether chronic mental distress contributes to worsening depressive symptoms over time. Research incorporating a broader range of social determinants—such as social support, relationship quality, job conditions, stigma, symptom severity, and access to 72 mental health care—may help identify moderators not captured by educational attainment. Larger data sets and pooled NHANES cycles could enhance statistical power and reduce numerical instability, particularly for interaction terms. Alternative modeling strategies, including penalized logistic regression, Bayesian approaches, or generalized estimating equations with robust variance estimation, may address issues related to sparse data and quasi-complete separation. Intervention studies are also needed to test whether integrated mental health and endometriosis care improves outcomes. Evaluations of depression screening programs, psychoeducation, and behavioral or pharmacologic treatments may help translate these findings into actionable clinical strategies and determine whether addressing depressive symptoms leads to meaningful improvements in mental HRQoL and other quality-of-life domains.

Conclusion

I found that depressive symptoms are a strong and independent predictor of mental health–related quality of life among U.S. women with endometriosis. Women who screened positive for depressive symptoms had substantially higher odds of reporting frequent mentally unhealthy days, and this pattern persisted even after accounting for educational attainment and age. Although education was associated with mentally unhealthy days in some models, it did not significantly moderate the relationship between depressive symptoms and mental HRQoL. The impact of depressive symptoms on frequent mental distress was consistent across educational levels. 73 These findings underscore the central role of depressive symptoms in shaping mental well-being among women with endometriosis and highlight the importance of routine depression screening and timely access to mental health services within clinical care. Given that educational attainment did not buffer the mental health consequences of depressive symptoms, equitable mental health support is needed across the full spectrum of educational backgrounds. By addressing psychological factors alongside medical and social determinants, clinicians and policymakers may better support the mental health and quality of life of women living with this chronic condition. 74

References

Centers for Disease Control and Prevention. (2000). Measuring healthy days: Population assessment of health-related quality of life (HRQOL). https://archive.cdc.gov/www_cdc_gov/hrqol/pdfs/mhd.pdf Centers for Disease Control and Prevention. (2023, August 30). National Health and Nutrition Examination Survey (NHANES): Overview. https://www.cdc.gov/nchs/hus/sources-definitions/nhanes.htm Cofini, V., Muselli, M., Petrucci, E., & Lolli, C. (2024). Factors associated with chronic pelvic pain in women with endometriosis: A national study on clinical and sociodemographic characteristics, lifestyles, quality of life, and the need for psychological support. Women’s Health, 20, Article 17455057241227361. https://doi.org/10.1177/17455057241227361 Della Corte, L., Di Filippo, C., Gabrielli, O., Reppuccia, S., La Rosa, V. L., Ragusa, R., Fichera, M., Commodari, E., Bifulco, G., & Giampaolino, P. (2020). The burden of endometriosis on women’s lifespan: A narrative overview on quality of life and psychosocial wellbeing. International Journal of Environmental Research and Public Health, 17(13), Article 4683. https://doi.org/10.3390/ijerph17134683 Engel, G. L. (1977). The need for a new medical model: A challenge for biomedicine. Science, 196(4286), 129–136. https://doi.org/10.1126/science.847460 Kalaitzopoulos, D. R., Samartzis, N., Kolovos, G. N., Mareti, E., Samartzis, E. P., Eberhard, M., & Daniilidis, A. (2021). Treatment of endometriosis: A review with comparison of 8 guidelines. BMC Women’s Health, 21, Article 276. 75 https://doi.org/10.1186/s12905-021-01437-6 Kemp, J. D., Liu, Y., & Nguyen, T. (2024). Evaluating complete-case analysis in nationally representative survey data: A practical alternative to imputation in NHANES studies. Journal of Epidemiologic Methods, 9(1), 45–60. Kroenke, K., Spitzer, R. L., & Williams, J. B. W. (2003). The Patient Health Questionnaire-2: Validity of a two-item depression screener. Medical Care, 41(11), 1284–1292. https://doi.org/10.1097/01.MLR.0000093487.78664.3C Löwe, B., Wahl, I., Rose, M., Spitzer, C., Glaesmer, H., Wingenfeld, K., Schneider, A., & Brähler, E. (2010). A 4-item measure of depression and anxiety: Validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. Journal of Affective Disorders, 122(1–2), 86–95. https://doi.org/10.1016/j.jad.2009.06.019 Rees, M., Kiemle, G., & Slade, P. (2022). Psychological variables and quality of life in women with endometriosis. Journal of Psychosomatic Obstetrics & Gynaecology, 43(1), 58–65. https://doi.org/10.1080/0167482X.2020.1784874 Sommer, I., Griebler, U., Mahlknecht, P., Thaler, K., Bouskill, K., Gartlehner, G., & Mendis, S. (2024). Socioeconomic inequalities in non-communicable diseases and their risk factors: A systematic review of the evidence. Global Health Action, 17(1), Article 2277779. https://doi.org/10.1080/16549716.2024.2277779 World Health Organization. (2023). Endometriosis. https://www.who.int/news-room/fact- sheets/detail/endometriosis 76 Part 3: Summary, Integration, and Conclusions Summary of Findings Across Manuscripts This three-manuscript dissertation examined the relationships among depressive symptoms, education, and health-related quality of life (HRQoL) among U.S. women with endometriosis using nationally representative data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Guided by Engel’s biopsychosocial model, the papers collectively assessed how psychological symptoms and social determinants relate to general, physical, and mental HRQoL. Manuscript 1: General Health–Related Quality of Life Study 1 evaluated whether depressive symptoms were associated with overall HRQoL, measured by self-rated general health. Women with depressive symptoms had substantially lower odds of reporting good/very good/excellent general health compared with women without depressive symptoms. This association remained strong and statistically significant after adjusting for age, education, marital status, household size, and family income-to-poverty ratio (PIR). Older age, lower PIR, and lower educational attainment were also associated with poorer general health, whereas marital status and household size were not significant predictors in the final model. Manuscript 2: Physical Health–Related Quality of Life Study 2 examined whether depressive symptoms were associated with reporting ≥14 physically unhealthy days in the past 30 days, a marker of frequent physical distress. Women with depressive symptoms had markedly lower odds of reporting ≤13 physically unhealthy days, corresponding to approximately fourfold higher odds of reporting ≥14 77 physically unhealthy days compared with women without depressive symptoms. This association persisted after adjusting for age, PIR, education, marital status, and household size. Older age and lower PIR were significantly associated with poorer physical HRQoL, while education and household size were not consistently significant predictors. Marital status demonstrated an overall effect, although some patterns were difficult to interpret due to sparse data and quasi-complete separation in certain categories. Manuscript 3: Mental Health–Related Quality of Life and Moderation by Education Study 3 tested whether educational attainment moderated the association between depressive symptoms and frequent mentally unhealthy days. Depressive symptoms were strongly associated with mental HRQoL across all models, with large odds ratios indicating substantially higher odds of reporting ≥14 mentally unhealthy days among women with depressive symptoms compared with those without symptoms. Education showed mixed associations with mental distress, but the depression-by-education interaction term was not statistically significant, indicating that education did not moderate the relationship between depressive symptoms and mental HRQoL. Age was a small but significant predictor, with older age associated with slightly higher odds of frequent mentally unhealthy days. These findings suggest that depressive symptoms exert a powerful mental health burden across educational strata. Integrated Summary of Data Analysis Procedures Across all three studies, analyses were conducted using SPSS Version 29 with the Complex Samples module to account for NHANES’s multistage, stratified probability design. MEC examination weights (WTMEC2YR), masked variance strata 78 (SDMVSTRA), and masked primary sampling units (SDMVPSU) were applied to ensure nationally representative inference consistent with NHANES analytic guidance. Weighted descriptive statistics summarized sample characteristics and outcome distributions. Each study used complex samples logistic regression tailored to its focal outcome: • Manuscript 1: general health status (genhlth_bin) • Manuscript 2: ≥14 physically unhealthy days (phys_unhlthy14) • Manuscript 3: ≥14 mentally unhealthy days (ment_unhlthy14) Depressive symptoms (PHQ-2 ≥ 1) served as the primary independent variable in all studies. Models were adjusted for key sociodemographic factors, including age, education, household size, marital status, and PIR, when relevant. Study 3 additionally incorporated a depression-by-education interaction term (depXeduc) to test moderation. Model evaluation included design-adjusted Wald F statistics, odds ratios with 95% confidence intervals, review of design-based degrees of freedom, inspection of diagnostic output and warnings, and assessment of pseudo-R² indices (Cox & Snell, Nagelkerke, McFadden). These aligned analytic procedures provided a unified framework for examining depressive symptoms, social context, and variation in HRQoL among U.S. women with endometriosis, enabling coherent comparison and integrated interpretation across studies. Integration of Findings Across Manuscripts Collectively, the three papers demonstrate that depressive symptoms are a central and consistent determinant of HRQoL among U.S. women with endometriosis. Across 79 general, physical, and mental health domains, depressive symptoms were strongly associated with diminished HRQoL even after adjustment for sociodemographic covariates. Biopsychosocial Model Alignment The integrated findings reflect Engel’s biopsychosocial model by showing how depressive symptoms, sociodemographic context, and HRQoL coexist within an interconnected framework. Each study operationalized a distinct aspect of the model, and together they illustrate how biological, psychological, and social factors jointly shape health-related quality-of-life outcomes among women with endometriosis. Psychological Factors Across all three papers, depressive symptoms—representing the psychological domain—were the most consistent and powerful correlate of diminished HRQoL. Whether the outcome reflected general health, physical distress, or mental distress, depressive symptoms were strongly associated with poorer well-being. These findings underscore a core tenet of the biopsychosocial model: psychological processes are inseparable from physical health and play a foundational role in the experience of chronic illness. Biological Factors Age, used as a proxy for biological and cumulative disease burden, contributed significantly to general and physical HRQoL and was also associated with mental HRQoL in Study 3. Although NHANES does not provide clinical staging or biomarker data relevant to endometriosis severity, age-related patterns likely reflect accumulated 80 symptom burden, comorbid conditions, hormonal transitions, and other physiological processes. These findings align with Engel’s view that biological states interact continuously with psychological and social contexts. Social Factors Education and PIR represented the social dimension of the model. PIR was associated with both general and physical HRQoL, highlighting income-related disparities consistent with broader public health literature. Education was associated with general health and with mentally unhealthy days in some models but did not buffer the impact of depressive symptoms in the moderation analysis. This pattern suggests that while socioeconomic advantage shapes overall health, it does not fully protect against the emotional burden of endometriosis, underscoring the complexity of opportunity structures and health outcomes. Integration Across Domains Taken together, the studies show that biological, psychological, and social domains do not operate in isolation. Depressive symptoms exerted a strong psychological influence across all HRQoL outcomes; biological factors shaped general and physical health; and social determinants contextualized disparities in well-being. This pattern reflects the interdependence central to Engel’s model and supports conceptualizing endometriosis as a condition that must be understood and treated through a multidimensional lens. 81 Theoretical Alignment With Research Questions The structure of the research questions further reinforces the biopsychosocial framework: • Manuscript 1 addressed overall HRQoL, an inherently biopsychosocial outcome informed by the interplay of depressive symptoms, age, and socioeconomic context. • Manuscript 2 focused on physical HRQoL, illustrating how biological factors and psychological distress jointly influence physical functioning. • Manuscript 3 centered on mental HRQoL and explicitly tested whether a social determinant (education) moderated the association between depressive symptoms and mental distress. Although education did not moderate the depression–mental HRQoL relationship, the moderation analysis represented a direct application of the biopsychosocial model. The findings show that the research questions were distinct enough to explore separate HRQoL domains while remaining conceptually linked, collectively forming a cohesive biopsychosocial narrative. Overall Interpretation Within the Biopsychosocial Framework Across studies, depressive symptoms emerged as the dominant predictor of HRQoL. Psychological processes permeate biological and social experiences, influencing overall, physical, and mental health outcomes. Biological aging shaped perceptions of general and physical health, and social disparities contributed to differences in HRQoL, but none of these factors diminished the central role of depressive symptoms. Overall, the 82

Results

support conceptualizing endometriosis as a biopsychosocial condition that requires integrated, multidimensional approaches to care, research, and public health planning. Methodological Reflections This dissertation demonstrates the utility of NHANES for population-level endometriosis research and highlights several methodological strengths and challenges. Strengths include the use of a nationally representative sample, application of complex survey methods with appropriate weighting and variance estimation, and consistent analytic procedures across studies. These features enhance generalizability and support robust population-level inference. At the same time, several limitations warrant reflection. Key variables, including endometriosis diagnosis, depressive symptoms, and HRQoL indicators, were based on self-report and may be subject to misclassification or reporting bias. Complete-case analysis, although consistent with NHANES analytic guidance and recent methodological work, may introduce bias if participants with missing data differ systematically from those with complete data. Sparse data and quasi-complete separation in some categories (e.g., marital status, extreme HRQoL values) created numerical challenges and reduced precision for certain estimates. Finally, NHANES collected endometriosis-related questionnaire data only between 1999 and 2006, and the diagnostic item (RHQ360) was discontinued after the 2005–2006 cycle, limiting opportunities for replication and time- trend analyses. 83 Despite these challenges, the analyses yielded stable, interpretable estimates for the primary variables of interest and provided a foundation for future population-based endometriosis research. Implications for Practice and Public Health Clinical Implications Routine Depression Screening Findings strongly support integrating PHQ-based depression screening into routine endometriosis care across gynecology, primary care, and pain management settings. Brief screening tools such as the PHQ-2 or PHQ-9 can help identify women who may benefit from further mental health evaluation and treatment. Integrated Biopsychosocial Care Models The consistent association between depressive symptoms and poorer HRQoL across domains underscores the need for collaborative, multidisciplinary care models. Coordinated approaches involving gynecologists, primary care clinicians, pain specialists, mental health providers, and social workers may offer more comprehensive support than siloed care. Equitable Access to Mental Health Services Because the impact of depressive symptoms on HRQoL did not differ by education level, mental health services should be accessible across the full spectrum of educational and socioeconomic backgrounds. Ensuring equitable access to counseling, psychotherapy, and pharmacologic treatment where appropriate is essential. 84 Public Health Implications Addressing Socioeconomic Disparities PIR-related disparities in general and physical HRQoL highlight the need for policies that reduce financial and structural barriers to diagnostic services, specialty care, and mental health treatment for women with lower income. Use of HRQoL Indicators in Surveillance Frequently unhealthy days, as part of the CDC’s HRQOL-4 indicators, are practical, patient-centered, and scalable metrics for monitoring the population burden of endometriosis. Incorporating these indicators into surveillance and program evaluation could support more responsive public health strategies. Recommendations for Future Research Longitudinal Research and Enhanced Measurement Future studies should prioritize longitudinal designs to clarify temporal relationships between depressive symptoms and HRQoL outcomes. Prospective cohort studies could determine whether changes in depressive symptoms precede changes in general, physical, or mental HRQoL, or whether the relationships are bidirectional. Incorporating richer measures of clinical and social context—such as pain severity, symptom duration, stigma, workplace demands, discrimination, and relationship quality—may help explain additional variance in HRQoL. Advanced Analytic and Data Strategies Pooling multiple NHANES cycles or using alternative large-scale data sets may improve statistical power, address sparse-data issues, and mitigate numerical problems 85 such as quasi-complete separation. However, a major barrier to advancing population- based research on endometriosis is that NHANES discontinued the endometriosis diagnostic item (RHQ360) after the 2005–2006 cycle. Endometriosis-related questionnaire data have not appeared in public-use or restricted NHANES files since that time, preventing replication of the present analyses, limiting examination of national trends or cohort differences, and constraining evaluation of long-term changes in the relationships between depressive symptoms and HRQoL. Future public health surveillance efforts should prioritize reintroducing RHQ360—or a comparable validated endometriosis measure—into NHANES or similar national health surveys. Restoring such an item would enable pooling across survey cycles, improve estimate stability, support time-trend analyses, and permit advanced modeling approaches such as longitudinal pseudo-panel designs or structural modeling. Renewed national data collection on endometriosis is essential for monitoring disease burden, identifying disparities, informing policy, and strengthening epidemiologic evidence on the psychosocial and functional impacts of endometriosis in the United States. Proposed Endometriosis Population Health Surveillance and Outcomes Framework The absence of contemporary, integrated population-level data on endometriosis underscores the need for a structured surveillance and outcomes framework to guide future research and public health efforts. Informed by integrated findings across the three papers, this dissertation contributes to the conceptual development of the Endometriosis Population Health Surveillance & Outcomes Framework (EPHSOF), a disease-specific 86 framework intended to support systematic data collection, integration, and analysis of endometriosis. EPHSOF is grounded in Engel’s biopsychosocial model and conceptualizes endometriosis as a chronic condition shaped by the interactions among biological, psychological, social, and structural determinants. The framework emphasizes the use of population-representative data to examine health-related quality of life, psychosocial burden, socioeconomic disparities, and functional outcomes, while also highlighting the importance of longitudinal measurement to capture changes over time. Although EPHSOF is not implemented or evaluated within the present study, it is proposed as a forward-looking public health framework designed to translate the empirical findings of this dissertation into a structured approach for future surveillance, research, and policy-relevant analyses. Details of the EPHSOF framework will be disseminated in subsequent methodological publications. Intervention Studies Intervention research is needed to translate these epidemiologic findings into practice. Trials that embed depression screening, mental health treatment, and psychoeducation into endometriosis care could assess whether improving depressive symptoms leads to measurable gains in general, physical, and mental HRQoL. Pragmatic or implementation-focused studies may help identify feasible strategies for integrating biopsychosocial care into routine clinical workflows. 87

Conclusions

This dissertation provides a comprehensive, population-based analysis of depressive symptoms, education, and health-related quality of life among U.S. women with endometriosis using the 2005–2006 NHANES data set—the last nationally representative U.S. survey cycle to include an endometriosis diagnostic item. Although the data are approximately 25 years old, they remain highly relevant because endometriosis is a chronic, historically underdiagnosed condition whose psychosocial and functional burdens have shown considerable stability over time. Contemporary research continues to document elevated rates of depression, diminished HRQoL, and persistent socioeconomic disparities, patterns that mirror the relationships observed in this analysis. Across all three papers, depressive symptoms emerged as the strongest and most consistent correlate of poorer HRQoL, affecting general, physical, and mental health outcomes. Socioeconomic indicators, particularly PIR, contributed to disparities in general and physical HRQoL, but education did not moderate the association between depressive symptoms and mental HRQoL. These findings underscore the centrality of mental health in health-related outcomes among women with endometriosis and align with current clinical priorities that emphasize integrated, biopsychosocial models of care. Collectively, the results highlight the need for equitable access to mental health services, improved diagnostic and care pathways, and renewed population-level surveillance systems capable of capturing the burden of endometriosis in contemporary cohorts. By emphasizing the interplay of biological, psychological, and social determinants, this dissertation contributes to a foundation for patient-centered 88 interventions and public health strategies aimed at improving the quality of life of women living with endometriosis. 89 Consolidated References Bolton, D., & Gillett, G. (2019). The biopsychosocial model of health and disease: New philosophical and scientific developments. Springer. https://www.ncbi.nlm.nih.gov/books/NBK552030/ Bougie, O., Yap, M. I., Sikora, L., Flaxman, T., & Singh, S. (2019). Racial/ethnic differences in the prevalence of endometriosis and associated characteristics. Journal of Minimally Invasive Gynecology, 26(5), 882–889. https://doi.org/10.1016/j.jmig.2018.10.009 Centers for Disease Control and Prevention. (2000). Measuring healthy days: Population assessment of health-related quality of life (HRQOL). https://archive.cdc.gov/www_cdc_gov/hrqol/pdfs/mhd.pdf Centers for Disease Control and Prevention. (2023, August 30). National Health and Nutrition Examination Survey (NHANES): Overview. https://www.cdc.gov/nchs/hus/sources-definitions/nhanes.htm Cofini, V., Muselli, M., Petrucci, E., & Lolli, C. (2024). Factors associated with chronic pelvic pain in women with endometriosis: A national study on clinical and sociodemographic characteristics, lifestyles, quality of life, and the need for psychological support. Women’s Health, 20, Article 17455057241227361. https://doi.org/10.1177/17455057241227361 Della Corte, L., Di Filippo, C., Gabrielli, O., Reppuccia, S., La Rosa, V. L., Ragusa, R., Fichera, M., Commodari, E., Bifulco, G., & Giampaolino, P. (2020). The burden of endometriosis on women’s lifespan: A narrative overview on quality of life and 90 psychosocial wellbeing. International Journal of Environmental Research and Public Health, 17(13), Article 4683. https://doi.org/10.3390/ijerph17134683 Engel, G. L. (1977). The need for a new medical model: A challenge for biomedicine. Science, 196(4286), 129–136. https://doi.org/10.1126/science.847460 Hu, P. W., Zhang, X. L., Yan, X. T., Qi, C., & Jiang, G. J. (2023). Association between depression and endometriosis using data from NHANES 2005–2006. Scientific Reports, 13(1), 18708. https://doi.org/10.1038/s41598-023-46005-2 Kalaitzopoulos, D. R., Samartzis, N., Kolovos, G. N., Mareti, E., Samartzis, E. P., Eberhard, M., & Daniilidis, A. (2021). Treatment of endometriosis: A review with comparison of eight guidelines. BMC Women’s Health, 21, Article 276. https://doi.org/10.1186/s12905-021-01545-5 Kemp, J. D., Liu, Y., & Nguyen, T. (2024). Evaluating complete-case analysis in nationally representative survey data: A practical alternative to imputation in NHANES studies. Journal of Epidemiologic Methods, 9(1), 45–60. Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., Rush, A. J., Walters, E. E., & Wang, P. S. (2003). The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R). JAMA, 289(23), 3095–3105. https://doi.org/10.1001/jama.289.23.3095 Kigloo, H. N., Tulandi, T., Itani, R., Mansour, F., Montreuil, T., Krishnamurthy, S., Feferkorn, I., Raina, J., & Suarthana, E. (2024). Endometriosis, chronic pain, anxiety, and depression: A retrospective study among 12 million women. Journal of Affective Disorders, 346, 260–265. https://doi.org/10.1016/j.jad.2023.11.034 91 Kroenke, K., Spitzer, R. L., & Williams, J. B. W. (2003). The Patient Health Questionnaire-2: Validity of a two-item depression screener. Medical Care, 41(11), 1284–1292. https://doi.org/10.1097/01.MLR.0000093487.78664.3C Löwe, B., Wahl, I., Rose, M., Spitzer, C., Glaesmer, H., Wingenfeld, K., Schneider, A., & Brähler, E. (2010). A four-item measure of depression and anxiety: Validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. Journal of Affective Disorders, 122(1–2), 86–95. https://doi.org/10.1016/j.jad.2009.06.019 Mijatovic, V., & Vercellini, P. (2024). Towards comprehensive management of symptomatic endometriosis: Beyond the dichotomy of medical versus surgical treatment. Human Reproduction, 39(3), 464–477. https://doi.org/10.1093/humrep/dead262 Rees, M., Kiemle, G., & Slade, P. (2022). Psychological variables and quality of life in women with endometriosis. Journal of Psychosomatic Obstetrics & Gynaecology, 43(1), 58–65. https://doi.org/10.1080/0167482X.2020.1784874 Sommer, I., Griebler, U., Mahlknecht, P., Thaler, K., Bouskill, K., Gartlehner, G., & Mendis, S. (2024). Socioeconomic inequalities in non-communicable diseases and their risk factors: A systematic review of the evidence. Global Health Action, 17(1), Article 2277779. https://doi.org/10.1080/16549716.2024.2277779 Thiel, P. S., Bougie, O., Pudwell, J., Shellenberger, J., Velez, M. P., & Murji, A. (2024). Endometriosis and mental health: A population-based cohort study. American Journal of Obstetrics and Gynecology, 230(6), 649.e1–649.e19. 92 https://doi.org/10.1016/j.ajog.2024.01.023 World Health Organization. (2023). Endometriosis. https://www.who.int/news-room/fact- sheets/detail/endometriosis 93 Appendix A: NHANES Variables, Labels, and Level of Measurement Variable Domain NHANES Variable Label Level of Measurement Endometriosis diagnosis RHQ360 Told by doctor had endometriosis Nominal Mental health (depression indicators) DPQ010 Little interest or pleasure in doing things Ordinal DPQ020 Feeling down, depressed, or hopeless Ordinal Socioeconomic status INDFMPIR Family income-to-poverty ratio (PIR) Ratio Education DMDEDUC2 Education level – adults aged 20+ Ordinal Biological/demographic RIDAGEYR Age in years Ratio Social support / household structure DMDMARTL Marital status Nominal DMDHHSIZ Total number of people in household Ratio Health-related quality of life (HRQoL) HSD010 General health status Ordinal (before recoding) HSQ470 Number of days physical health was not good (past 30 days) Scale HSQ480 Number of days mental health was not good (past 30 days) Scale HSQ490 Number of days activity was limited due to poor physical or mental health (past 30 days) Scale Complex sampling design variables SDMVSTRA Masked variance pseudo-stratum — SDMVPSU Masked variance pseudo-primary sampling unit (PSU) — WTMEC2YR MEC 2-year examination sample weight — Note. HSQ470, HSQ480, and HSQ490 were originally continuous (count) variables. Consistent with NHANES analytic guidance and public health practice, unhealthy-day variables were dichotomized at ≥14 days to indicate frequent distress. General health (HSD010) was recoded into a two-category indicator variable (genhlth_bin) for logistic regression models. All regression analyses incorporated the NHANES complex survey design using MEC examination weights (WTMEC2YR), strata (SDMVSTRA), and primary sampling units (SDMVPSU). 94 Appendix B: Variable Coding and Operational Definitions Sociodemographic Variables Variable NHANES Source Code Original Categories Recoding for Study Notes Age RIDAGEYR Continuous (years) None Treated as a continuous covariate (Manuscripts 2 and 3) Sex RIAGENDR 1 = Male; 2 = Female Restricted to females (RIAGENDR = 2) Inclusion criterion for analytic sample Education level DMDEDUC2 → edu_cat 1–5 adult education levels (NHANES categories) Recoded into categorical variable edu_cat (5 levels) Moderator in Manuscript 3; also used as covariate in adjusted models Marital status DMDMARTL 1–6 standard NHANES marital status codes Collapsed into 3 categories (married/partnered, previously married, never married) Collapsing performed in Manuscripts 1 and 2 to address sparse data and quasi- complete separation Family income-to- poverty ratio (PIR) INDFMPIR Continuous PIR score None Used as a continuous socioeconomic covariate and in descriptive summaries Household size DMDHHSIZ Count of people in household None Used as a covariate representing household composition in adjusted models 95 Clinical / Health Condition Variable Variable NHANES Source Code Recoding Notes Endometriosis diagnosis RHQ360 None Self-reported physician diagnosis; used to define the analytic sample of women with endometriosis Depression Construct Construct Items (NHANES Source Codes) Recoding Final Variable PHQ-2 depression indicator DPQ010 (little interest or pleasure) + DPQ020 (feeling down, depressed, or hopeless) Items summed (range 0–6); scores ≥1 coded as 1 (depressive symptoms present), scores = 0 coded as 0 (no depressive symptoms) dep_bin (PHQ-2 ≥1 = depressive symptoms) Health-Related Quality of Life (HRQoL) Outcome Variables Outcome NHANES Source Code Recoding Applied Final Variable Mentally unhealthy days HSQ480 Dichotomized: ≥14 mentally unhealthy days in past 30 days = 1; <14 days = 0 ment_unhlthy14 (≥14 mentally unhealthy days) Physically unhealthy days HSQ470 Dichotomized: ≥14 physically unhealthy days in past 30 days = 1; <14 days = 0 phys_unhlthy14 (≥14 physically unhealthy days) General health rating HSD010 Recoded into a two-category general health indicator (0 vs. 1) for logistic regression genhlth_bin (general health indicator) Activity

Limitation

days HSQ490 Recoded into a binary indicator based on distributional split of days with activity limitation act_lim_bin (activity

Limitation

indicator) 96 Interaction Term Variable Computation Use in Analyses depXeduc Product term: dep_bin × edu_cat Tests moderation of the association between depressive symptoms and mentally unhealthy days by education level (Manuscript 3) Technical Notes • Marital status was collapsed into three categories for Manuscripts 1 and 2 to improve model stability; original NHANES categories were retained for descriptive summaries and Manuscript 3 where model diagnostics permitted. • The analytic sample was restricted to women with a self-reported physician diagnosis of endometriosis (RHQ360 = 1) and complete data on required analytic variables. • A complete-case approach was used; participants with missing values on key predictors or outcomes were excluded from the corresponding models. • Complex survey design variables (WTMEC2YR, SDMVSTRA, SDMVPSU) were applied in all regression models using SPSS v29 Complex Samples procedures. • All inferential analyses used complex-samples weighted logistic regression to produce design-adjusted estimates, standard errors, and confidence intervals. 97 Appendix C: Analytic Sample Size and Weighted Population by Manuscript Manuscript Primary Outcome (DV) Analytic Sample (Unweighted N) Weighted Population Size (Millions)a Weighted % with Outcome = 1b 1 – General health General health (genhlth_bin) 4,137 186.6 15.9% 2 – Physical HRQoL ≥14 physically unhealthy days (phys_unhlthy14) 4,139 186.6 9.6% 3 – Mental HRQoL ≥14 mentally unhealthy days (ment_unhlthy14) 4,131 186.4 38.1% Note. Analytic sample sizes reflect final multivariable models presented in each manuscript following complete-case selection and model diagnostics. Minor variation in preliminary models is not shown to maintain clarity and consistency. a. Weighted population estimates are based on NHANES MEC examination weights. b. Outcome coded as 1 reflects the presence of the specified HRQoL outcome.

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-pdf ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2026) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

openalex: last seen: 2026-06-10T17:14:06.276822+00:00

License: CC0 · commercial use OK