Reciprocal Association Between Endometriosis and Depressive Symptoms: Using Data from NHANES 2005–2006

Introduction: Endometriosis, a chronic inflammatory condition affecting approximately 10% of reproductive-aged women, is frequently underdiagnosed and commonly co-occurs with depressive symptoms. However, the nature and directionality of this association remain unclear. Prior work (Hu et al., 2023) has linked depressive symptom severity to endometriosis, but not the reverse association. We aimed to (1) reproduce Hu et al.’s findings linking depressive symptoms to endometriosis, (2) examine the association in the opposite direction, and (3) assess the robustness of both associations using matched analyses. Methods: Using data from NHANES’s 2005–2006 cycle, we conducted (1) survey-weighted logistic regression with endometriosis (yes/no) as the outcome and PHQ-9 scores (continuous and categorical) as the exposures; (2) linear and multinomial regression with PHQ-9 scores (continuous and categorical: none/moderate/severe) as outcomes and endometriosis status as the exposure; and (3) exact and nearest-neighbor matching on age, race, and income, followed by conditional logistic regression. Preliminary exploration of machine learning methods (e.g., causal forests) was also conducted. Results: The reverse association analysis indicated a significant relationship between endometriosis and moderate (vs. no) depressive symptom severity (OR = 2.11, 95% CI: 1.12–4.00). Matched analyses further strengthened both associations (endometriosis as outcome: OR = 2.87, 95% CI: 1.42–5.80; depressive symptoms (yes/no) as outcome: OR = 2.32, 95% CI: 1.21–4.45). Discussion: While evidence supports a reciprocal association between endometriosis and depressive symptoms, the cross-sectional design limits causal interpretation. Findings highlight the clinical value of screening for depressive symptoms in patients with endometriosis, and vice versa, warranting future causal investigation.