Courtesy of Dora Koller

Endometriosis is a disease that affects roughly 10 percent of women worldwide, according to the World Health Organization. 

The symptoms of endometriosis — a disease wherein tissue similar to the uterus lining grows outside the uterus — reach beyond the realm of gynecology and affect the entire body and mind. Researchers at the Yale School of Medicine’s Department of Psychiatry investigated potential mental comorbidities of endometriosis, finding that the disease has epidemiologic and genetic correlations with depression, anxiety and eating disorders. 

Despite the prominence of endometriosis and its often-recognizable symptoms such as chronic period pain and gastrointestinal issues, the disease is widely undiagnosed. Dora Koller, a postdoctoral fellow in the department of psychiatry and first author of the study, explained that this is due to the dismissal of the concerns of women and the broader societal stigma surrounding menstruation.

“It’s [the underdiagnosis of endometriosis] because of medical misogyny,” Koller said. “Women are not taken seriously, you know that something is wrong with your body — you know it’s not normal how you feel, but no one takes it seriously. Not society, or medical professionals. In my opinion, it is not too difficult to think someone has endometriosis when they have all the symptoms.”

Koller said that the disease is most often diagnosed after women have decided they want to conceive, as infertility is another prominent symptom of endometriosis. This has historical roots, Koller explained, as the function of women in society was for so long viewed to be solely reproduction, and therefore people only begin to care when that function is disrupted. 

The underdiagnosis of endometriosis is further exacerbated by limited discussion of periods, explained Koller and Gita Pathak, a postdoctoral fellow in the department of psychiatry and second author on the study. This limited discussion makes defining “normal” when it comes to period pain challenging. Koller explained that a woman might think it is normal to be unable to stand for two days due to debilitating pain.

“It often just gets misclassified as period pain for most women, like it’s a common thing you have to endure during your periods,” Pathak said. “But then someone has to tell you that’s not normal, to go see a doctor and not just shrug it away as a woman thing, a woman thing you have to endure.”

This study is the first to consider both epidemiological and genetic data in analyzing mental health comorbidities of endometriosis, and the first to identify eating disorders as one such comorbidity. The study began by investigating phenotypic associations between endometriosis and depression, anxiety and eating disorders. 

In considering data from the UK biobank on 270,000 women, the study found that this correlation was quite high, going beyond the standard mental comorbidities that come with experiencing chronic pain from any disease. 

“Our findings highlight that the association of endometriosis with depression, anxiety and eating disorders is independent of chronic pain,” Renato Polimanti, associate professor of psychiatry at the School of Medicine and senior author of the study, wrote to the News. “This is a very important result, because it indicates that the mechanisms responsible for psychiatric comorbidities are more complex than previously expected.”

To verify this finding, the researchers conducted a genome-wide association study and found high genetic associations between depression, anxiety and eating disorders with endometriosis. Using pleiotropic analysis to find shared genes between depression and endometriosis, the researchers also identified a gene, DGKB, that is highly expressed in female reproductive tissue as well as many different brain regions.  

Furthermore, based on this genetic analysis, Koller and her colleagues found that depression and anxiety are actually causal to endometriosis, not the other way around, which is what was previously expected. The identification of genetic associations also suggests a shared pathogenesis, Polimanti explained.

This work was personal for Koller, as she has endometriosis and wanted to apply her training in psychiatry to the investigation of the disease. 

“For me, it was personal motivation,” Koller said. “I suffer from endometriosis and it was undiagnosed for fifteen years … we do research about psychiatric disorders in general, Gita and I, and I really wanted to see if there was anything between endometriosis and psychiatry.”

Koller hopes that general practitioners and gynecologists use this study to better understand endometriosis systemically. 

Polimanti emphasized that when treating patients affected by endometriosis, mental health should be considered. 

“Unfortunately, although endometriosis is a common disorder with a large impact on women’s health, it is still severely under-investigated,” Polimanti wrote to the News. “Accordingly, we need more attention from scientists and funding agencies to support research that can disentangle the complexity of endometriosis and lead to more effective treatments.”

Based on their findings of genetic correlations, Koller discussed the potential of precision medicine, which is medicine personalized to individual patients. Genetic analysis could be used as a tool to predict the likelihood of psychiatric comorbidity development in individuals suffering from endometriosis. 

The department of psychiatry at the Yale School of Medicine was founded in 1930.