Endometriosis, Chronic Pain, and Changes in the Brain

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Full transcript of the original video, lightly edited for readability.

I want to revisit something we first started mapping back in 2019 because a recent 2024 MRI study has brought the conversation right back where we began this study reported that women with endometriosis showed structural brain patterns that were different from women who had chronic pelvic pain without the disease and that distinction matters because when we talk about endometriosis affecting mental health most people immediately assume we mean the emotional burden of living in pain of course chronic pain medical dismissal and disrupted relationships contribute to depression and anxiety.

But that is not the only mechanism I am talking about the possibility that endometriosis creates repeated hormonal inflammatory and neurological signals that can change how the brain functions and potentially how it physically adapts over time it is biology beginning to catch up with the model we've been developing for years endometriosis and adenomyosis do not simply create pain they create cyclical changes in estrogen signaling and inflammation the brain is one of the most estrogen sensitive organs in the body with receptors throughout regions that regulate memory cognition fear processing and emotional control.

So when estrogen signaling rises and falls around the cycle the brain responds that feeling of dread or sudden gloom isn't automatically a mindset problem the brain is responding to chemistry in endometriosis this is more intense because the disease involves a complete flip on normal receptor function in endometriotic tissue estrogen receptor beta can be more than 100 times higher than in normal tissue when ER-beta becomes dominant it can suppress normal signaling interfere with progesterone and support inflammation does this same imbalance exist throughout the brain it's a legitimate biological question estrogen receptor beta is involved in circuits connected to fear anxiety and emotional processing repeated estrogen signaling combined with inflammation and pain could place constant pressure on the same neural networks that control mood and behavior this mechanism allows estrogen to cross the blood-brain barrier directly in endometriosis estrogen signaling isn't controlled only by the ovaries lesions can produce estrogen locally we described endometriotic tissue as an estrogen factory because it develops the machinery like steroidogenic factor 1 expressed up to 12,000 fold higher to manufacture its own localized hormonal environment once estrogen reaches the brain it can affect dopamine signaling serotonin transmission and memory retrieval this gives us an explanation for why brain fog becomes worse during flares and why coordination or emotional reactions can feel impossible to control the brain is forced to adapt as the environment changes again people often argue that endometriosis doesn't cause hormone spikes because blood tests show normal estrogen but that's too narrow endometriosis is a disease of abnormal signaling the brain responds to receptor activation exposure timing and inflammatory context receptor level surges that laboratory reports Miss.

Let us return to the 2024 MRI study researchers compared women with confirmed endometriosis women with chronic pelvic pain without endometriosis and healthy pain free controls they asked a vital question are brain differences simply from chronic pain or does endometriosis show a unique pattern they found that women with endometriosis had increased gray matter volume in the left cerebellum and lingual gyrus compared to those with other chronic pelvic pain in contrast those with non endometriosis pain showed decreased volume in the right cerebellum the overall structural pattern was not identical pain severity such as dysmenorrhea and dyspareunia correlated with gray matter changes in regions involved in sensory integration and attention while pain plays a major role the structural pattern suggests the brain is repeatedly responding to a unique set of sensory inflammatory and hormonal inputs these findings are consistent with neuroplasticity the brain adapting to what it repeatedly experiences this process doesn't require permanently elevated systemic estrogen it only requires recurrent biological pressure and the same circuits to be stimulated again and again we have proposed that shared upstream epigenetic vulnerabilities produce different downstream effects depending on the tissue involved in reproductive tissue it's abnormal estrogen and inflammation in the nervous system it's changes in pain processing cognition and mood shared roots different outcomes this provides a logical explanation for why symptoms are cyclical even when systemic tests appear normal the brain is forced to adapt as the environment shifts this study creates convergence between molecular biology neurochemistry and brain imaging reinforcing the model we've proposed.

Let us be precise endometriosis does not need to create a dramatic increase in blood estrogen to affect the brain it only needs to create repeated cycles of receptor level signaling inflammation pain transmission and neuroimmune activation over time those repeated signals leave a structural pattern we arrived at these subjects estrogen receptors mitochondria and brain chemistry because the mechanisms continued pointing in the same direction when this explanation finally makes someone's brain fog or anxiety feel understandable it isn't us saying it's all in her head it is recognizing that the brain is a physical organ responding to physical signals the pelvis and the brain were never separate science is simply beginning to measure the conversation between them.