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The Insidious Histamine-Hormone Connection

Updated: May 15

This month, we're diving in to possible triggers to the release of histamine in the body.

Today, let's explore the mysterious ways that hormonal imbalances have the potential of increasing your histamine mediated symptoms.

Sex Hormones: Estrogen & progesterone

If you have struggled with infertility, it’s possible that histamine may be playing a role.

While histamine and mast cell activation impact all genders, women tend to feel the impact much more. Mast cell related health conditions are more commonly seen in women due to higher estrogen.

Here's why: estrogen stimulates mast cell degranulation. (1, 2)

Histamine normally ebbs and flows with women’s menstrual cycles. In the first part of the menstrual cycle (the follicular phase) leading up to ovulation, estrogen rises. Then comes ovulation. After ovulation (the luteal phase) progesterone rises to create changes in the uterine lining. It drops off before the beginning of the next cycle.

Histamine is correlated to estrogen, so is highest just before ovulation when estrogen is also high. Histamine also rises right before your period when progesterone has dropped. Histamine mediated symptoms can worsen during these times.

If you have PMS and have a worsening of other histamine-mediated symptoms including migraines, anxiety, or breast pain then your PMS may have histamine involvement.

Histamine is involved in normal menstruation. The problem is not histamine, but rather its connection with imbalanced hormones.

When Sex Hormones are Imbalanced

Role of Estrogen

Histamine can stimulate more estrogen to be released from the ovaries. If your histamine levels are high, then it follows that you will have higher estrogen levels.

Estrogen then signals mast cells to release more histamine by binding to estrogen receptor sites. It becomes a vicious cycle where estrogen and histamine fuel the production of one another.

Estrogen Clearance

Estrogen and histamine share some of the same clearance pathways such as COMT (Catechol-O-Methyltransferase) and other methylation pathways.

If these pathways aren’t optimal due to genetic variations or other factors that impede them, you will not be able to clear these substances from your body efficiently.

This inability to clear estrogen and histamine further compounds the problem.

Role of Progesterone

Progesterone on the other hand acts as the brakes on histamine. Progesterone signals the mast cells to stop releasing histamine. (3)

If you have adequate progesterone, things are okay, but if your levels are low, there is nothing to signal “stop releasing histamine”.

Puberty & Peri-menopause

Puberty and the transition into menopause are times when women experience a shift in their hormones. This can often result in a state of estrogen dominance. This dominance means that estrogen is higher in relation to progesterone than it should be.

Another way to think of this imbalance would be to consider it a progesterone deficiency. Either way, the ratio of estrogen to progesterone is upset.

In puberty, estrogen can be high due to overproduction, environmental exposure, or an inability to break down or clear estrogen. Thus begins the estrogen dominance.

In perimenopause, progesterone is the first hormone to decline.

With either situation, whether it is from higher estrogen, or from declining progesterone, the result is the same – estrogen dominance and higher histamine levels.

Without enough progesterone to stabilize mast cells and signal “stop”, those cells will keep releasing histamine.

Anecdotally there are many women who develop histamine symptoms during perimenopause. Women who have never had allergies before can develop them at this time, along with other histamine symptoms.

Hormones can decline in an irregular or inconsistent manner during this time of life, resulting in inconsistent histamine symptoms. Could this be you?

Correcting the Imbalance

It is important that you work with a practitioner that understands the importance of both the level of hormones and their ratios to one another. Request a comprehensive hormone panel to explore if sex hormone imbalance is contributing to your symptoms.


Is this the first time you've heard of the histamine and hormone connection? Curious to know if you have potential histamine or mast cell issues contributing to hormonal imbalances?

Get started by joining our free master class we call The Histamine Connection. It's a live webinar we host every month, and it won't cost you a dime. In this class, we explore how histamine and/or mast cell issues show up in the body, and we get you started on solutions so that you can feel better.

Plan to join us live - there's a Live Q&A component at the end! And of course, a replay goes out to all who register.

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