Endometriosis and Mental Health: The Brain-Body Connection

I spent years thinking I was broken in two separate ways: my body hurt, and my mind was a mess. I had depression that wouldn't respond fully to medication. Anxiety that would spike randomly. A sense of doom that felt disproportionate to whatever was happening around me. My therapist was great. My antidepressant helped. But something was still off, like I was fighting a war on two fronts and winning on neither.

It wasn't until I understood the mechanics of my endometriosis that I realized these weren't separate problems. They were the same problem, expressing itself through different biological channels. My brain wasn't broken. It was responding exactly as it should have been to years of chronic inflammation.

Let me explain what I didn't know for so long.

It's Not "Just Stress"—It's Neuroimmunology

One of the most gaslighting statements I ever heard was: "Your pain is making you depressed." Yes. Duh. But that's not the whole story. It's not just that chronic pain is psychologically wearing (though it absolutely is). It's that endometriosis literally alters your brain chemistry through inflammation.

Here's the mechanism: Endometrial lesions produce inflammatory cytokines—IL-6, IL-8, TNF-alpha. These are chemical messengers that signal danger. In healthy amounts, they're helpful. But in endometriosis, the peritoneal cavity is essentially a swamp of pro-inflammatory cytokines. Some are small enough to cross the blood-brain barrier. Once they're in your central nervous system, they activate microglia (your brain's immune cells) and alter the synthesis of neurotransmitters like serotonin and dopamine.

In one study, depression and anxiety rates were significantly elevated in endometriosis patients—up to three times higher than the general population. These weren't people who were depressed about having endometriosis. These were people whose brains were being bathed in inflammatory compounds that directly impair mood regulation.

Another mechanism involves the NLRP3 inflammasome—a protein complex that, when activated, kicks your immune system into overdrive. Research shows that endometrial lesions activate this inflammasome, flooding the body with inflammatory signals. Your brain is listening to all of this. It's literally trying to protect you by heightening anxiety (making you hypervigilant) and dampening mood (conserving energy for a perceived emergency).

The Estrogen Dominance Piece

Endometriosis is characterized by estrogen dominance—not necessarily high estrogen in the blood, but extremely high local concentrations of estrogen in lesions and the peritoneal cavity. Estrogen has receptors all over your brain, particularly in regions governing mood and emotion (the amygdala, prefrontal cortex, hippocampus).

When estrogen signaling is dysregulated, it disrupts the tryptophan-kynurenine pathway—the biochemical route your body uses to convert tryptophan (an amino acid) into serotonin. Too much estrogen can shunt tryptophan down the kynurenine pathway instead, producing compounds like quinolinic acid that actually damage neurons and increase neuroinflammation. You could be taking an SSRI and still feeling depressed because the fundamental substrate for serotonin synthesis has been diverted.

The Trauma Layer: Medical Gaslighting as a Risk Factor

There's also a psychological and social dimension that compounds this. Many of you spent years—sometimes decades—being dismissed. Your pain was "not that bad." Your symptoms were "in your head." You were told to "just have a baby" or "exercise more" or "eat better." You were gaslit by medical systems that couldn't see what was actually wrong.

That's medical trauma. That's real. And research from my colleagues in trauma-informed medicine shows that this kind of repeated invalidation from authority figures changes how your nervous system responds. You become hypervigilant. You catastrophize (sometimes appropriately). You develop anxiety about healthcare itself.

The neuroinflammation from endometriosis + the psychological trauma from delayed diagnosis + the chronic pain rewiring your nociceptive pathways = a compounded mental health crisis that antidepressants alone cannot fully address.

Why This Matters for Treatment

Here's what this changes: If your mental health issues are partly driven by the inflammatory cascade of endometriosis, then treating only the mental health symptoms won't fully resolve them. You can go to therapy. You can take medication. Both are valuable. But if you're not also reducing the inflammatory burden in your body, you're paddling upstream.

Conversely, reducing inflammation—through surgery (removing lesions), dietary changes (reducing pro-inflammatory foods), nervous system retraining (downregulating your fight-or-flight response), and sometimes anti-inflammatory supplementation—can significantly improve depression and anxiety. You're addressing the root cause, not just the symptom.

In one study of endometriosis patients who underwent excision surgery (which removes lesions), there was a significant improvement in depression and anxiety scores in the months following surgery. Not because they were magically "fixed," but because the inflammatory driver was removed.

What You Can Actually Do

First: You're not broken. Your brain is responding appropriately to the inflammatory state of your body. That's not weakness or drama.

Second: Address both sides. Yes, continue with therapy and medication if they're helping. That's not wasted effort. But also treat the endometriosis itself—through whatever combination of approaches makes sense for you (surgery, lifestyle changes, nervous system work). Mental health and physical health are not separate domains.

Third: Be gentle with the timeline. Neuroinflammation doesn't resolve overnight. Your brain will need time to recalibrate. You might feel better gradually, not dramatically. That's still progress.

And fourth: Find providers who understand this connection. Too many doctors are still practicing as if the brain and body exist in separate universes. You need someone who gets that endometriosis is a whole-system disease—that inflammation in your pelvis affects your mood, your sleep, your cognition, and your sense of self.

You're not losing your mind. Your mind is reacting to your body's crisis. Once we address that crisis, you might be surprised at what becomes possible on the mental health side.