Hormones

Clinically we see histamine as a root problem with symptomatic endometriosis. In endometriosis, higher estrogen levels are linked to more active and abundant mast cells in the affected tissue. These mast cells release inflammatory substances that can contribute to pain and swelling. Research shows that when endometriotic cells are exposed to estrogen, they attract mast cells and trigger them to release their contents—adding to the inflammation and discomfort often experienced with this condition.

Histamine is an important risk factor in the neuroinflammation associated with endometriosis.

Building on this, histamine not only amplifies inflammation but also disrupts nervous system function, potentially heightening the pain response in individuals with endometriosis. Histamine can sensitize peripheral nerve endings and contribute to central sensitization—where the nervous system becomes hyper-reactive to pain stimuli. This means that even mild inflammation or hormonal fluctuations can trigger disproportionate pain responses. Additionally, histamine may influence hormone signaling, creating a feedback loop where elevated estrogen promotes mast cell activity, mast cells release histamine, and histamine further exacerbates estrogen dominance. This cyclical relationship highlights the need to address histamine metabolism as part of a comprehensive strategy for managing endometriosis symptoms.

Hormone replacement therapy is a marvel of medicine. And it has some negatives we should note. Postmenopausal women taking HRT have a higher risk of new onset asthma. This is believed to be estrogen mediated. We know that 30-40% of women who had asthma experience a worsening of their symptoms during PMS especially during perimenopause when estrogen levels can be higher.

This estrogen-inflammation connection becomes particularly relevant during perimenopause, a time marked by hormonal fluctuations that can intensify systemic and localized inflammatory responses. Estrogen, while protective in many ways, can also stimulate immune cells like mast cells, leading to the release of histamine and other inflammatory mediators. These shifts can contribute to a wide range of symptoms often reported in perimenopause—such as headaches, bloating, breast tenderness, mood swings, and joint pain—that may be partially driven by histamine sensitivity or overload. As estrogen levels spike and drop unpredictably, the immune system may become more reactive, creating a cycle of inflammation that exacerbates perimenopausal symptoms. Recognizing this link can help guide more personalized approaches to managing the transition, including attention to histamine load and immune modulation.

If you’ve been pregnant, and all your hista-worries have miraculously disappeared then you’re witnessing the marvel of DAO. Most women transform into anti-histamines during pregnancy.

Why? To Protect their babies from exposure to excess histamine.

To help keep histamine in check, the placenta produces a large amount of an enzyme called diamine oxidase (DAO) during pregnancy. DAO breaks down histamine and acts as a protective barrier, helping to prevent high histamine levels from reaching either the mother or the baby.

That doesn’t mean pregnancy isn’t a time when histamine plays crucial roles. Healthy physiologic levels maintain pregnancies. It’s only when it gets out of hand that we see rashes, pre-eclampsia and rhinitis develop and plague pregnant women.

Progesterone plays a helpful role in keeping histamine levels in balance. It does this by calming down mast cells (the cells that release histamine during allergic or inflammatory reactions) and boosting the activity of an important enzyme called DAO, which helps break down histamine in the body.

This is important because estrogen does the opposite—it can cause mast cells to release more histamine and may slow down DAO, leading to a buildup of histamine. By balancing these effects, progesterone can ease symptoms of histamine intolerance, like headaches, skin rashes (like hives), and digestive discomfort.

Many people notice these benefits during the luteal phase of their menstrual cycle—the time after ovulation—when progesterone levels are naturally at their highest.

Mast cells have special receptors on their surface that respond to estrogen, a hormone that naturally fluctuates in the body—especially in women.

When estrogen levels rise or change, mast cells can become more sensitive and more likely to release chemicals that trigger symptoms like itching, swelling, or breathing problems. This is one reason why some people notice their allergies or asthma symptoms get worse around their period, during perimenopause, or with hormone treatments.

Research has shown that estrogen can make mast cells more active. In animal studies, when estrogen was added back after it was removed, mast cell activity returned—showing just how much this hormone can influence immune responses.

Understanding this connection can help explain why allergic symptoms sometimes seem to follow hormonal patterns.

We can’t just slap an estrogen patch on someone with histamine problems and call it a day.

That’s why it’s important to consider histamine intolerance (HIT) in women who experience new or worsening symptoms after starting hormone replacement therapy (HRT).