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Sex, Mast Cells, and Autoimmunity

There are sex-based differences in immune function that contribute to a higher incidence of both mast cell activation and autoimmune conditions in female bodies, as compared to male bodies.

Hormones, chromosomes, and epigenetic factors are all possible differences that exist between the sexes that could be influencing immune function.

Generally, females mount a stronger immune response than males do. Males are more susceptible to parasitic infection (1) and they almost always die younger than females (2). This may seem like great news for females -- sorry fellas! -- but females are more likely to suffer from autoimmune conditions.

Additionally, being female is a risk factor for polyautoimmunity (having more than one autoimmune condition). Read more here.

Sex influences biological factors such as hormone production. Mast cells have sex hormone receptors setting them up to interact with a variety of sex hormones. Translation: hormones have the ability to trigger your mast cells to release different chemicals. This means your body's hormones can potentially impact the function of your mast cells, and everything they release and all they potentially impact!

Estrogen and the Immune System

Sex hormones' primary job is to regulate reproductive function, but they also have a critical role in many other body systems and tissues.

Estrogen has been widely studied and been shown to modulate the immune system. Mast cells have estrogen receptors on their surface (4).

When estrogen binds to these receptors, mast cells are activated and degranulate (5). When they degranulate, it means they release a myriad of chemicals / mediators. (See more on that here.) Through this action, estrogen contributes to MCAS. In our last article, we looked at how mast cells are involved in autoimmune progression.

Is it possible that estrogen’s impact on mast cells is one of the many mechanisms of how sex hormones impact autoimmunity?

Is Estrogen the Connection Between MCAS and Autoimmunity?

Research is virtually non-existent, but here’s what we know:

  • Many different immune cells (including mast cells) have estrogen receptors that have a role in regulating immune signaling and function (6)

  • Estrogen is one of the triggers for both MCAS and autoimmunity conditions.

  • Mast cells release a wide variety of inflammatory mediators such as cytokines.

  • Cytokines can contribute to abnormal estrogen activity in conditions such as rheumatoid arthritis (7).

  • Estrogen signals the release of histamine from mast cells—a mediator known to be involved in autoimmunity (8).

We think this is compelling evidence to connect estrogen, mast cell activation and autoimmunity. Keep in mind we are holistic nutritional consultants—not researchers. It’s the holistic part of us that looks to understand how everything is connected.

What do you think?

We’d love to hear your feedback.


Curious to understand this histamine connection and tie it in to your symptoms a little bit more?

Consider joining us at our next live class we call The Histamine Connection. It's a free Master Class that is designed to help you make that connection to how histamine is impacting your day to day life, and how nutrition can be of support.

Register for the next live class (listed on the left), or register for the pre-recorded version (listed on the right). You can register for either class here.

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BHRT has had the negative effect of causing severe histamine intolerance. I've stopped estrogen replacement but no relief of symptoms. Would progesterone help in my case?

Replying to

This is a question to discuss with your doctor. Estrogen signals the release of histamine and progesterone puts the breaks on it, so it makes sense that it would help. You want to work with a doctor who is doing saliva hormone testing to make sure this is the right approach for you.

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