Understanding the Link Between PMDD and Mast Cell Activation Syndrome (MCAS)
- 6 days ago
- 4 min read
Premenstrual Dysphoric Disorder, or PMDD, is often described as a severe form of PMS. However, many women with PMDD are told their hormone levels are normal. This can feel confusing and more importantly invalidating.
In clinic, we see PMDD to be linked to immune system dysregulation, particularly Mast Cell Activation Syndrome, known as MCAS.
Understanding the connection between PMDD and MCAS helps explain why symptoms can feel extreme, cyclical and difficult to treat with hormone therapy alone.
What Is PMDD?
PMDD is a severe, cyclical mood disorder that occurs during the luteal phase of the menstrual cycle, usually in the one to two weeks before menstruation.
Common PMDD symptoms include:
Severe irritability or rage
Anxiety or panic
Depression or hopelessness
Tearfulness
Brain fog
Insomnia
Bloating and breast tenderness
Headaches or migraines
Symptoms typically improve shortly after menstruation begins.
Importantly, most women with PMDD have normal oestrogen and progesterone levels. The issue appears to be sensitivity to hormonal fluctuations rather than abnormal hormone production.
What Is Mast Cell Activation Syndrome (MCAS)?
Mast Cell Activation Syndrome, or MCAS, is a condition in which mast cells release inflammatory chemicals too easily or in excessive amounts.
Mast cells are immune cells located throughout the body, including:
The gut
The skin
The respiratory tract
Around blood vessels
Near nerve endings
In areas of the brain involved in mood regulation
When mast cells are activated, they release substances such as histamine, prostaglandins and cytokines.
In MCAS, this release can be disproportionate and lead to symptoms affecting multiple systems.
How PMDD and MCAS Are Connected
The link between PMDD and MCAS lies in the relationship between hormones, histamine and the nervous system.
1. Oestrogen Triggers Mast Cells
Oestrogen can directly stimulate mast cells to release histamine.
This means that during natural hormonal fluctuations in the menstrual cycle, mast cells may become more active in women with MCAS.
2. Histamine Affects Mood and the Brain
Histamine is not only involved in allergies. It is also a neurotransmitter.
Elevated histamine can:
Increase anxiety
Disrupt sleep
Heighten emotional reactivity
Increase sensory sensitivity
Promote neuroinflammation
If histamine levels rise during the luteal phase, this may intensify PMDD symptoms.
3. A Feedback Loop Between Oestrogen and Histamine
Oestrogen stimulates mast cells to release histamine.Histamine can stimulate further oestrogen production.
This creates a feedback loop.
In women with PMDD and MCAS, normal hormonal shifts may amplify immune activation, which in turn worsens mood symptoms.
Why PMDD Symptoms Worsen Before a Period
PMDD occurs during the luteal phase, when:
Oestrogen fluctuates
Progesterone rises and then falls
The nervous system becomes more sensitive
If mast cells are unstable, these hormonal changes can trigger increased release of histamine and inflammatory mediators.
This may lead to:
Sudden rage or irritability
Intense anxiety
Feeling overwhelmed
Insomnia
Migraines
Gastrointestinal flares
Skin symptoms such as flushing or itching
For some women, PMDD with MCAS presents as both mood symptoms and physical inflammatory symptoms before menstruation.
Signs PMDD May Be Linked to MCAS
You may wish to consider mast cell involvement if PMDD symptoms occur alongside:
Cyclical migraines
Cyclical urticaria or flushing
Worsening allergies before menstruation
Increased food sensitivity premenstrually
Gut flares before your period
A known diagnosis of MCAS
These patterns suggest that immune activation may be contributing to premenstrual mood instability.
Why Hormone Therapy Alone May Not Be Enough
Conventional treatment for PMDD often includes SSRIs or hormonal contraception.
While these can be helpful, they may not address underlying mast cell activation.
If MCAS is contributing to PMDD symptoms, stabilising mast cells and reducing overall inflammatory load may reduce the severity of premenstrual mood changes.
For some women, improving immune stability leads to:
Less intense mood swings
Shorter symptom duration
Improved sleep
Better stress tolerance
The menstrual cycle remains, but the inflammatory reaction becomes less severe.
PMDD and MCAS: A Neuroimmune Perspective
PMDD and MCAS sit at the intersection of the endocrine, immune and nervous systems.
In simple terms: Normal hormone changes + An over reactive immune system = Exaggerated emotional and physical symptoms
This perspective helps explain why women with PMDD often feel that their reactions are out of proportion to the situation. The response is biological, not a personal failing.
A Functional Medicine Approach to PMDD and MCAS
At The Autoimmune Clinic, we consider PMDD within the wider context of immune health, mast cell stability and inflammatory load.
When assessing PMDD and MCAS, we consider:
Evidence of mast cell activation
Histamine related symptoms
Gut health, SIBO, SIFO
Histamine breakdown and clearance pathways
Environmental triggers, such as mould or chemicals
Nervous system regulation
Addressing mast cell activation in women with PMDD can often reduce symptom severity and improve quality of life.
The connection between PMDD and MCAS offers a broader understanding of severe premenstrual symptoms.
For many women, PMDD is not simply about hormones. It is about how the immune system reacts to hormonal change. If you experience severe cyclical mood symptoms alongside signs of mast cell activation, exploring the link between PMDD and MCAS may provide important answers.
If this resonates with your experience, you are welcome to book a discovery call to explore whether a personalised, root cause approach may be appropriate for you.
