Epidemiologic and Genetic Associations of Endometriosis With Depression, Anxiety, and Eating Disorders

Abstract

ImportanceEndometriosis is a common chronic gynecologic pathology with a large negative impact on women’s health. Beyond severe physical symptoms, endometriosis is also associated with several psychiatric comorbidities, including depression and anxiety.ObjectiveTo investigate whether pleiotropy contributes to the association of endometriosis with depression, anxiety, and eating disorders.Design, Setting, and ParticipantsThis genetic association study was performed between September 13, 2021, and June 24, 2022, in 202 276 unrelated female participants. Genotypic and phenotypic information from the UK Biobank was combined with genome-wide association statistics available from the Psychiatric Genomics Consortium (11 countries), the Million Veteran Program (US), the FinnGen study (Finland), and the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium (5 countries).Main Outcomes and MeasuresThe main outcomes were the phenotypic and genetic associations of endometriosis with anxiety, depression, and eating disorders.ResultsA total of 8276 women with endometriosis (mean [SD] age, 53.1 [7.9] years) and 194 000 female controls (mean [SD] age, 56.7 [7.9] years) were included in the study. In a multivariate regression analysis accounting for age, body mass index, socioeconomic status, chronic pain–related phenotypes, irritable bowel syndrome, and psychiatric comorbidities, endometriosis was associated with increased odds of depression (odds ratio [OR], 3.61; 95% CI, 3.32-3.92), eating disorders (OR, 2.94; 95% CI, 1.96-4.41), and anxiety (OR, 2.61; 95% CI, 2.30-2.97). These associations were supported by consistent genetic correlations (rg) (depression rg, 0.36, P = 1.5 × 10−9; anxiety rg, 0.33, P = 1.17 × 10−5; and eating disorders rg, 0.61, P = .02). With the application of a 1-sample mendelian randomization, the genetic liabilities to depression and anxiety were associated with increased odds of endometriosis (depression: OR, 1.09; 95% CI, 1.08-1.11; anxiety: OR, 1.39; 95% CI, 1.13-1.65). A genome-wide analysis of pleiotropic associations shared between endometriosis and psychiatric disorders identified 1 locus, DGKB rs12666606, with evidence of pleiotropy between endometriosis and depression after multiple testing correction (z = −9.46 for endometriosis, z = 8.10 for depression, P = 5.56 × 10−8; false discovery rate q = 4.95 × 10−4).Conclusions and RelevanceThese findings highlight that endometriosis is associated with women’s mental health through pleiotropic mechanisms. To our knowledge, this is the first large-scale study to provide genetic and phenotypic evidence of the processes underlying the psychiatric comorbidities of endometriosis.

Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study

“…Specifically, our results demonstrate significant associations between genetically predicted depression/dysthymia and the following conditions: Endometriosis (OR = 1.47, 95% CI 1.27–1.71), PCOS (OR = 1.43, 95% CI 1.28–1.59), AUB (OR = 1.41, 95% CI 1.20–1.66), and Ovarian cysts (OR = 1.36, 95% CI 1.20–1.55). These findings align with other MR studies that have also suggested depression as a risk factor for PCOS 21 and endometriosis 46 .…”

Mood disorders influencing endometriosis and adenomyosis: Mendelian randomisation study

“… 24 Recent studies have suggested the possibility of a common genetic predisposition to both diseases, which is an alternative causality consistent with the results of our study. Koller's research showed that the coexistence of endometriosis with multiple psychiatric disorders is likely to be associated with genetic pleiotropy, 25 and Li's study found that endometriosis induced pain sensitisation, anxiety and depression by modulating brain gene expression and electrophysiology. 26 …”

What Is Behind? Impact of Pelvic Pain on Perceived Stress and Inflammatory Markers in Women with Deep Endometriosis

“…Epidemiological studies have helped quantify the socioeconomic impact and quality of life of women affected by endometriosis [2][3][4][5][6][7][8]. This research has revealed not only the substantial financial burden associated with endometriosis but also highlighted the importance of holistic approaches that consider not only medical aspects but also the social and psychological impacts of this condition.…”

“…This burden affects approximately 10% of women globally and represents a significant concern for women's health [2][3][4]. This condition has been the subject of intensive study, and significant advancements have been made in understanding it [5][6][7]. Gruber et al (2021) have sought to elucidate the variable and often intense nature of the pain experienced by affected women [11].…”