How Endometriosis Impacts Mental Health and Affects the Brain

Author: Evelyn Fistler

Editor: Martha W

Intro— What Is Endometriosis?

Endometriosis is known as a chronic inflammatory disease that is estrogen-dependent, affecting individuals with a uterus. This disease occurs when endometrial-like tissue, known as lesions, reside outside the uterine lining. Severe symptoms include pelvic pain, dysmenorrhea, non-menstrual pelvic pain, and dyspareunia, with about 26% of individuals who have it have reported infertility. While it most commonly grows outside of the uterus and resides within the pelvic cavity, endometrial-type tissue can grow to other parts of the body as well (As-Sanie, et al, 2025).

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Endometriosis and Cognition

Endometriosis and cognition are an aspects within the field of neurological research that desperately needs further investigation, as there are limited studies and reviews regarding uterine research. With the limited studies provided, evidence does suggest that many individuals with endometriosis self-reported cognition impairment, highlighting difficulties with inhibition, attention, and memory (Berryman & Machado, 2025).

Berryman and Machado (2025) also discuss other studies regarding fMRI results in individuals with endometriosis-associated chronic pelvis pain, with structural changes and altered functional connectivity between the insular cortex and central pain networks.Narrowing down to interior structures, there is further evidence that shows there is decreased functional connectivity between the right anterior insula and the middle frontal gyrus in some individuals with endometrioses-associated chronic pelvic pain.  These changes mostly occurred in those who had displayed pain cognition in attention, expectancy, and appraisal. Because the middle front gyrus focuses on reorienting attention to potential pain inputs within the body, such as intense pressure and extreme heat, it seems that disruption to the circuitry may contribute to pain in individuals with endometriosis. Along with decreased functional connectivity between the right anterior insula and the cerebellum, which is known to have a dominant inhibitory role in pain modulation, fMRI research further suggests that because of these disruptions within these brain regions, those with endometriosis experience enhanced pain, which results in negative attention impacts (Berryman & Machado, 2025).

Affect on Mental Health

Koller (et al, 2023) provides further insight on how deep endometriosis affects the body, specifically mental health. Significant findings suggest chronic pain to be associated with an increased risk for depression and other psychiatric disorders. A clinical study found that 86% of individuals with endometriosis and chronic pelvic pain (sample size of 8,276) were found to have depression. The study also suggests that endometrial effects on brain regions such as hippocampus, amygdala, and insula in mice cause pain sensitization and mood disorders.

Li (et al, 2018) provides evidence that endometriosis is associated with a higher likelihood of developing depression and anxiety disorders; consistent with the fact that the affected areas (insula, amygdala, and hippocampus) play key roles in pain, anxiety, and depression. During the behavioral study, mice with endometriosis were observed to display more anxious behavior than those without, suggesting parallels in human behavior. This research provides evidence that endometriosis alters brain gene expression, leading to noticeable changes in mental health.

Even though there is a correlation between endometriosis and mental health issues, there is still a lack of expanded research on how endometriosis affects the brain as there are other aspects to consider. Lack of treatment  or education on how severely each individual is affected is a common issue that results in inadequate care towards both physical and mental health.

Biological Changes

Bashir (et al, 2023), provides evidence for neurological changes in mice with endometriosis, notability observing an increase in microtonal soma size within regions such as the cortex, hippocampus, thalamus, and hypothalamus. Through behavioral assessment, Bashir (et al, 2023) noticed changes in mice behavior, specifically burrowing and food removal from pellets. Further investigation revealed that mice with increased abdominal pain and hyperalgesia refrain from food retrieval and burrowing habits. Analysis of microglia cell bodies suggests that microglia grow larger in size when activated, and that in this study, there was an increase in glial cells, with microglia size observed to be larger in those with endometriosis. 

What Are Microglial Cells?

Microglia are macrophages that live in the brain, acting as immune cells to remove unwanted substances and dead cells, inducing healing to an injured area. Microglia activate via enlargement after detecting nerve injuries, inflammation, or ischemia. However, further damage can be induced because activated microglia are suggested to promote inflammation and further aggravate neurodegenerative diseases (Nakaso, 2024).

The two types of microglia consist of M1 and M2, with M1 being neurotoxic and inducing inflammation, and M2 being  neuroprotective, inducing anti-inflammatory responses. Because endometriosis lesions release inflammatory markers, this causes microglia to activate. Further analysis shows in Bashir (et al, 2023) provides results of the mice study that give evidence of central nervous system-wide glial activation, further demonstrating that microglial enlargement is a critical aspect of pain sensitivity in those with endometriosis through the release of pro-inflammatory cytokines and chemokines. 

Endometriosis in Other Organs

Interestingly, it seems endometriosis can reside in other places of the body besides the uterus. In another study conducted by Dr. Neisani Samani, within implanted endometrial cells in mice, these cells can migrate to other organs, including the brain which produces central nervous effects (Endometriosis.org, n.d.). Cerebral Endometriosis is described as an indication of endometrial tissue within the brain, affecting the cerebellum. Although rare, women with endometriosis are known to have a higher chance of experiencing psychiatric conditions, which cerebral endometriosis is suggested to play a role in influencing. Further symptoms besides constant pain would include heightened sensitivity to hormonal changes, modifications in gene activity, and lesions that affect different areas of the brain that play a role in mood regulation. Considering the study that found that glial cells play a major role in endometriosis, it is also notable to analyze how glial cell abnormalities are further involved with mood disorders (such as depression and anxiety) and behavior (Cronkleton, 2023).

Conclusion

The limited information on how endometriosis affects women cognitively shows the importance of women’s healthcare and research. Because of unknown variables and constant changes in research, studies such as the ones provided above should be well understood to move forward with newer research, where more education on how endometriosis can manifest within other organs and affect the brain can be sought, with in addition to potential treatments for the disease.

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References

As-Sanie S, Mackenzie SC, Morrison L, et al. Endometriosis: A Review. JAMA. 2025;334(1):64–78. doi:10.1001/jama.2025.2975

Bashir, S. T., Redden, C. R., Raj, K., Arcanjo, R. B., Stasiak, S., Li, Q., Steelman, A. J., & Nowak, R. A. (2023). Endometriosis leads to central nervous system-wide glial activation in a mouse model of endometriosis. Journal of neuroinflammation, 20(1), 59. https://doi.org/10.1186/s12974-023-02713-0

Cronkleton, E. (2023, November 14). What is Endometriosis in the Brain (Cerebral Endometriosis)? Healthline. https://www.healthline.com/health/endometriosis-in-the-brain#symptoms

Endometriosis.org. (n.d.). ASRM2015: Endometriosis may infiltrate the entire body –  Endometriosis.org. Copyright 2005-2011 endometriosis.org. https://endometriosis.org/news/congress-highlights/asrm2015-endometriosis-may-infiltrate-the-entire-body/

Koller, D., Pathak, G. A., Wendt, F. R., Tylee, D. S., Levey, D. F., Overstreet, C., Gelernter, J., Taylor, H. S., & Polimanti, R. (2023). Epidemiologic and Genetic Associations of Endometriosis With Depression, Anxiety, and Eating Disorders. JAMA network open, 6(1), e2251214. https://doi.org/10.1001/jamanetworkopen.2022.51214

Nakaso K. (2024). Roles of Microglia in Neurodegenerative Diseases. Yonago acta medica, 67(1), 1–8. https://doi.org/10.33160/yam.2024.02.001

Ashlee Berryman, Liana Machado, Cognitive Functioning in Females with Endometriosis-Associated Chronic Pelvic Pain: A Literature Review, Archives of Clinical Neuropsychology, Volume 40, Issue 5, August 2025, Pages 1066–1080, https://doi.org/10.1093/arclin/acaf003

Li, T., Mamillapalli, R., Ding, S., Chang, H., Liu, Z. W., Gao, X. B., & Taylor, H. S. (2018). Endometriosis alters brain electrophysiology, gene expression and increases pain sensitization, anxiety, and depression in female mice. Biology of reproduction, 99(2), 349–359. https://doi.org/10.1093/biolre/ioy035