Mast Cells and PMS: Uncovering the Link Between Hormones, Histamine, and NOS3
Photo by Erriko Boccia on Unsplash.
Do you dread getting your period each month? If you find yourself dealing with irritability, headaches, nausea, bloating, or restless sleep in the lead-up to menstruation, you’re not alone - 30-40% of menstruating women experience clinically significant symptoms related to pre-menstrual syndrome (PMS). I count myself lucky not to be among them, but it wasn’t always this way. In my early teens, and then again in 2018, I would experience symptoms like mood swings, bloating, fatigue, and breast tenderness in the days (and sometimes weeks) leading up to my period.
If this is you, you’ve probably been told “this is hormones”, that it’s just part of being a woman, and that the best way to deal with it is to go on some form of birth control.
This is not strictly true.
While hormones do play a role in PMS, they’re not the only factor at play. There’s a reason why I experienced worse PMS symptoms at the times that I did - and why I don’t suffer from them now.
One of the major reasons for strong hormone-related symptoms at different times of the month is what your mast cells are up to. Many of the women that I see and treat in clinic are struggling with mast cell activation syndrome (MCAS) and/or histamine intolerance, and they don’t even know it!
Furthermore, research suggests that the enzyme Nitric Oxide Synthase 3 (NOS3), which plays an important role in blood flow, can play a significant role in how PMS symptoms manifest.
In this blog post, we’re going to explore how mast cells, histamine, and NOS3 interrelate in the context of PMS, and some specific strategies that can help alleviate symptoms.
First things first: let’s talk mast cells.
What Are Mast Cells?
Mast cells are a type of immune cell involved in allergic reactions and inflammation. They reside in tissues such as the skin, lungs, and digestive system, and are best known for releasing histamine, which can lead to symptoms like itching, swelling, and redness during allergic responses.
But they do so much more than that. Mast cells are also involved in a wide range of inflammatory processes beyond allergies and are believed to play a role in many chronic health conditions.
Mast cells contain substances that can either trigger or modulate inflammation, such as histamine, cytokines, and prostaglandins. As part of your immune system’s first line of defence, mast cells are critical in the body's immune response, but can also contribute to chronic inflammation if their activation becomes dysregulated. This happens in MCAS when mast cells are constantly creating inflammation, resulting in a wide range of symptoms, including conditions like autoimmune diseases, heart disease, and neurological and mental health conditions.
Mast Cells and Hormonal Fluctuations
The menstrual cycle is marked by natural hormonal fluctuations, particularly estrogen and progesterone, which affect a range of bodily functions, including immune responses. Mast cells are highly sensitive to hormonal changes, especially estrogen, which has been shown to stimulate mast cell activation. This means that mast cells release more pro-inflammatory molecules, which can increase your body’s total inflammatory load. During the luteal phase of the menstrual cycle, when estrogen levels peak, mast cells are more likely to release histamine and other inflammatory mediators.
One of the most relevant inflammatory molecules released by mast cells in the context of female sex hormones is histamine. Histamine is a potent inflammatory mediator that can contribute to common PMS symptoms like bloating, breast tenderness, headaches, and mood disturbances. It plays many roles in the body, ranging from modulating gut motility to acting as a neurotransmitter, which means that it can affect a wide range of body systems when elevated. The elevation in estrogen during the luteal phase means that individuals may experience a flare-up of symptoms associated with excess histamines, especially if they have heightened mast cell sensitivity already.
On the other hand, progesterone has a stabilising effect on mast cells, potentially reducing inflammation. However, in cases where there is MCAS, this natural balancing effect may not function properly, resulting in exaggerated responses to hormonal fluctuations, particularly during the luteal phase.
How Mast Cells Contribute to PMS Symptoms
When mast cells are activated, they release histamine and other inflammatory mediators, leading to a cascade of effects throughout the body. Here’s how this can contribute to common PMS symptoms:
Bloating and Water Retention
Histamine release increases the permeability of blood vessels, which can cause fluid to leak into surrounding tissues. This leads to swelling and bloating, a common symptom of PMS, especially in the abdominal region.Breast Tenderness
Inflammation caused by histamine can lead to increased blood flow to the breast tissue, resulting in sensitivity and discomfort. This is one of the hallmark symptoms of PMS, often worsened by mast cell activation.Mood Swings and Irritability
Histamine also plays a role in regulating mood. Higher histamine levels can contribute to feelings of irritability, anxiety, and even depression, which are common emotional symptoms of PMS. Histamine affects neurotransmitter pathways in the brain, influencing mood regulation and emotional well-being.Headaches and Migraines
Histamine can cause blood vessels in the brain to dilate, which is known to trigger headaches and migraines. For those sensitive to mast cell activation, this process can be more pronounced during the luteal phase, leading to more frequent or intense headaches.Fatigue
Chronic inflammation resulting from mast cell activation can lead to fatigue, another common PMS symptom. As the body becomes burdened by inflammatory processes, it expends more energy to manage the inflammation, leading to feelings of exhaustion and a lack of energy.
Any (or all?!) of these symptoms ring a bell? There’s a good chance that you’re experiencing the effects of excessive histamines, especially if your symptoms worsen at your time of the month.
The Role of NOS3 in Mast Cell Activation and PMS
NOS3 is an enzyme that plays a vital role in the production of nitric oxide (NO), a molecule that helps regulate blood flow and maintain healthy blood vessel function. Nitric oxide is crucial for promoting vasodilation (the widening of blood vessels), which improves circulation and reduces blood pressure. Proper nitric oxide production can help manage inflammation and ease symptoms like swelling, fatigue, and headaches.
Interestingly, NOS3 activity is known to be influenced by regular movement. Exercise and movement have been shown to stimulate NOS3 production, which in turn can help improve blood flow, support detoxification, and reduce inflammation. By enhancing nitric oxide levels, regular physical activity can counterbalance the effects of mast cell activation and histamine release, potentially reducing PMS symptoms.
Strategies for Managing Mast Cell Activation and PMS
If mast cells are contributing to PMS symptoms, several natural strategies can help mitigate their effects:
Movement and Exercise
Regular movement is one of the most effective ways to stimulate NOS3 production and improve nitric oxide levels. Activities such as walking, jogging, yoga, or resistance training can help promote healthy circulation, reduce inflammation, and support immune regulation. By improving blood flow, movement may alleviate symptoms like bloating, fatigue, and headaches.Mast Cell Stabilisation Through Diet
A diet rich in anti-inflammatory foods can support mast cell stability. Focus on incorporating foods that are rich in antioxidants, like fruits and vegetables, and those high in omega-3 fatty acids (found in fish, flaxseeds, and walnuts). Supplements like quercetin, vitamin C, and magnesium have been shown to stabilise mast cells and reduce the inflammatory response. For some people, a diet with plenty of B vitamin-containing foods can also be helpful.Stress Reduction and Mind-Body Practices
Chronic stress can exacerbate mast cell activation, so adopting stress-reduction techniques such as yoga, meditation, and deep-breathing exercises can help regulate the immune system and reduce inflammation. These practices support parasympathetic nervous system activation, which helps counterbalance the effects of the stress response and may reduce mast cell activation.Dietary Considerations for Histamine Intolerance
People who experience mast cell activation may be more sensitive to histamine, which is found in certain foods. Reducing the intake of histamine-rich foods (like aged cheeses, fermented foods, and alcohol) can help minimise symptoms like bloating and headaches during the luteal phase, but these diets are restrictive, so I don’t recommend adopting them long term..Anti-Inflammatory Supplements
Supplements such as curcumin, vitamin D, and omega-3 fatty acids have been shown to support inflammation reduction and mast cell regulation. These can be particularly helpful for individuals with PMS who are experiencing heightened levels of inflammation and mast cell activation.
When Do You Need to Address Mast Cell Activity?
Regular movement and exercise, anti-inflammatory nutrition, and stress-reduction techniques are all essential tools for supporting the body's ability to manage mast cell activation, reduce inflammation, and improve overall well-being during the menstrual cycle. These are all strategies that you can implement easily and relatively safely (though do be aware that over-the-counter supplements can sometimes have side effects, so always check before starting a new supplement and go slowly with it.
But if mast cells are significantly impacting your quality of life each time your have your period - or during other parts of the month - then it might be a good idea to take the next step and find a practitioner who can help you. I truly believe that women’s bodies are made so perfectly, we’re not meant to be in pain each month. Not me, not you, or anyone else.
Women deserve better.