An Early Look at Histamine and Endometriosis Tissue

From conversations with patients who have said there is a correlation between histamine and endometriosis symptoms, I thought it may be time to look into what has actually been done in the research on it. As we all know, when we are suffering with something that offers little support to us through the general medical route (see my previous post entitled "Endometriosis and Acupuncture"), we can feel like we need to take matters into our own hands.

When we feel unsupported, we often look to other people with similar experiences to find ways to either validate or ameliorate what we're going through; I am talking about Instagram research a bit.... Even I have seen "research" on Instagram on how endometriosis is a histamine problem, and if you take an antihistamine, people are claiming alleviation of symptoms. I take self-reports seriously, but I really do think it's also worth a deep dive to find out where this information comes from, and is it really something I should be suggesting to my patients here, or is it a bunch of click-bait?

Whether histamine plays a part in endometriosis is a question that it seems researches are only starting to dig into. What I want to know is: what exists so far and where are the gaps where we don't yet have answers?

A quick word on histamine and mast cells

Histamine is best known for allergies: itchy eyes, hives, etc... and histamine is stored in mast cells.

Mast cells are immune cells that sit in your tissues and release histamine and other inflammatory chemicals when they're triggered. Mast cells also sit close to nerve endings which obviously matter a lot when we're talking about pain.

Research in endometriosis and mast cells:

A 2022 study found significantly more mast cells in endometriotic lesions than in the uterine lining of the same patients, along with higher levels of a specific growth factor that helps mast cells multiply and survive.

A 2025 review in the International Journal of Biological Sciences goes a bit further: oestrogen, which drives the growth of endometriosis lesions, also activates the mast cells inside them. Once activated, they release histamine and another signal called "FGF2", which make nearby pain nerves more sensitive and, over time, increase pain signalling. The nerves and mast cells then feed each other in a loop that will continue to amplify pain.

A 2025 gene expression analysis in Frontiers in Medicine points the same way, finding changes in the genes that make and break down histamine. This suggests a lesion environment where histamine lingers and inflammation persists. In this paper, the authors does suggest H1 antihistamines as a possible treatment for endometriosis.

There is a lot we don't know yet.

I couldn't find any controlled trial testing antihistamines or a low histamine diet for endometriosis symptoms. The studies above are mostly lab-based work and reviews of mechanism, not meta analyses, so they give us a reason that histamine might matter and leave open whether targeting it actually could be helpful in real world scenarios. I'd rather say that plainly than suggest that there is an easy fix, as the evidence doesn't support any, yet.

Acupuncture as a part of the solution?

This part is interesting, but a little complicated. A 2021 systematic review and meta-analysis in the Journal of Pain pooled animal studies on skin mast cells and acupuncture analgesia (studies on animals, pain relief, and using acupuncture, and "sham" or fake acupuncture).

Manual and electro-acupuncture both causes significant mast cell degranulation at the needle site, while sham acupuncture did not. For manual acupuncture, the more degranulation, the greater the pain relief. Histamine and adenosine were among the mediators involved. Most of the studies has a moderate risk of bias, and the authors call for further work to confirm the findings.

So mast cells appear to amplify pain inside endometriosis lesions, while their activation in the skin at an acupuncture point is linked to pain relief. These are 2 different tissues doing different jobs, and nobody yet knows how the two fit together, or whether acupuncture's effect on endometriosis pain involves mast cells at all. I'm not claiming it does, but it's something I'm keeping an eye on.

This is early research, and I expect a lot more from it. As new studies come out, I will be keeping my ear to the ground and will update this post with what the new information means for treatment, whether it confirms what we think or whether it changes it. In the meantime, what we do know is that acupuncture can help to modulate the pain that comes from endometriosis; what we don't know is whether or not histamine modulation is a mechanism of action.

Unravelling the Intricate Link: Mast Cells and Estrogen-Induced Pain Sensitization in Endometriosis. Int J Biol Sci. 2025;21(13):5891-5904.

Exploring the therapeutic potential of H1-antihistamines in endometriosis: a gene regulation-based perspective. Front Med. 2025. doi:10.3389/fmed.2025.1538368

Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology. Front Immunol. 2022;13:961599. doi:10.3389/fimmu.2022.961599

Bae S, et al. The Role of Skin Mast Cells in Acupuncture Induced Analgesia in Animals: A Preclinical Systematic Review and Meta-analysis. J Pain. 2021. doi:10.1016/j.jpain.2021.06.006