The Overlapping Storm: PMDD, Hypermobile Bodies, and Histamine Imbalance
PMDD, EDS, MCAS & Histamine: where’s the overlap?
For those navigating life with Ehlers-Danlos Syndrome (EDS) or Hypermobility Spectrum Disorder (HSD), it often feels like health challenges come in clusters. EDS and HSD are a group of connective tissue conditions characterised primarily by joint hypermobility, skin that is unusually stretchy or fragile, and a tendency toward tissue fragility. These disorders often go underdiagnosed or misunderstood because their symptoms can be subtle or overlap with other conditions. For those living with EDS or HSD, daily life may involve managing chronic pain, frequent joint dislocations, and a host of other systemic issues stemming from the connective tissue abnormalities that underpin these syndromes. Understanding the wide-ranging impacts of EDS and HSD is crucial, as these disorders often do not occur in isolation but rather coexist with or contribute to other complex health conditions.
One particularly intriguing area of emerging research is the link between EDS/HSD and conditions such as Premenstrual Dysphoric Disorder (PMDD), Mast Cell Activation Syndrome (MCAS), and histamine intolerance. These overlapping disorders share common threads in immune dysregulation and inflammatory responses, suggesting that the connective tissue abnormalities in EDS/HSD might influence or exacerbate symptoms of PMDD and MCAS. Exploring these connections not only sheds light on the multifaceted nature of EDS and HSD but also opens pathways for more integrated and effective approaches to treatment and symptom management.
But what ties these seemingly distinct conditions together? Increasingly, we’re learning that immune system dysregulation, hormonal sensitivity, and histamine overload are often at the root. In a functional medicine approach, the goal isn’t just to manage symptoms, it’s to understand why the body is reacting this way, and then support it naturally at its very foundation. Understanding the interplay between hormones, mast cells, connective tissue and neurodivergence, can help clarify why symptoms in these populations, are so often complex, cyclical and difficult to manage with a one-size-fits-all approach.
PMDD – what is it?
PMDD – or Pre menstrual dysphoric disorder is far beyond just “bad PMS” as so many may be prone to thinking. PMDD is a cyclical mood disorder that affects approximately 3-9% of menstruating individuals. Unlike PMS, which negatively affects nearly half of women in their menstruating years, PMDD involves more severe emotional, cognitive and physical symptoms that typically emerge in the luteal phase (days 15-28) of their cycle and subside or lessen once bleeding begins.
Common emotional symptoms include:
Sudden onset depression or anxiety
Mood volatility and emotional hypersensitivity
Irritability, intrusive thoughts, or a sense of overwhelm
Social withdrawal, brain fog, and, in severe cases, suicidal ideation
Physical symptoms often mirror or amplify EDS-related issues:
Joint pain and muscular discomfort
Migraines, bloating, and gastrointestinal upset
Insomnia and profound fatigue
Changes in appetite, breast tenderness, and heavy bleeding
When layered on top of conditions like EDS/HSD, PMDD can intensify the baseline challenges associated with connective tissue disorders, pain, fatigue, dysautonomia, and lead to periods of significant physical and emotional instability (1).
Neurodivergence, Hormones, and PMDD
Recent research has revealed that PMDD is more prevalent among neurodivergent populations, particularly those with autism or ADHD. For example, studies have found that up to 92% of autistic individuals report PMDD-like symptoms, as do nearly half of those with ADHD (2).
This connection may be due to several overlapping factors:
Genetic susceptibility: PMDD has a strong genetic component, as do ADHD and EDS.
Dopamine dysregulation: People with ADHD often experience chronically low dopamine, which may be especially sensitive to hormonal fluctuations.
Sensory amplification: Those with autism or sensory processing sensitivity may find hormonal changes particularly disruptive to emotional and physical regulation.
For individuals with EDS/HSD, where neurodivergence is also more common, these sensitivities can converge, amplifying the impact of each condition (3).
For some it is a really difficult combination.
The Histamine Connection: Mast Cells and Menstrual Cycles
Histamine, a molecule involved in immune response, digestion, and neurotransmission, may also be a significant yet under recognised factor in the symptom profile of people with EDS/HSD and PMDD.
In those with MCAS, mast cells release excessive histamine in response to triggers such as allergens, heat, or stress. However, hormonal fluctuations, particularly in oestrogen and progesterone, can also activate mast cells (4). This hormonal-mast cell link helps explain why histamine-related symptoms often worsen at certain points in the menstrual cycle, even in people who do not meet the full criteria for MCAS.
Histamine & the Menstrual Cycle:
Days 1–5 (Menstruation): Oestrogen and progesterone are low; inflammation is often high.
Days 6–14 (Follicular Phase): Rising oestrogen can stimulate mast cells, leading to fatigue, joint pain, itching/rashes, mood shifts, headaches and more.
Day 14 (Ovulation): Oestrogen peaks, triggering a notable histamine surge. Many report flares in physical and emotional symptoms at this point.
Days 15–28 (Luteal Phase): Progesterone increases, ideally stabilising mast cells, but in PMDD, the body may not respond to progesterone adequately, leaving histamine unchecked.
This cycle illustrates why symptoms of PMDD, MCAS, and EDS/HSD often seem synchronised, and why addressing histamine may be a key therapeutic strategy (5).
How I can help:
Given the overlapping nature of these conditions, symptom management requires an individualised, responsive approach.
Instead of suppressing each symptom in isolation, a root cause approach asks:
How can we reduce histamine load, stabilise the nervous system, and support hormonal resilience?
Food First: Natural Ways to Lower Histamine and Calm the System
Supporting histamine balance through diet is foundational.
· A Low-Histamine Diet: Reducing foods that are aged, fermented, cured, or leftover (think: wine, cheese, vinegar, processed meats, and leftovers) can be hugely helpful as a first strategy. Many people with MCAS or PMDD report flare-ups after consuming these but some may have other triggers and hence an individualised, targeted approach is best.
· Supporting DAO Enzyme Activity: DAO (diamine oxidase) breaks down histamine in the gut. Nutrients like vitamin B6, vitamin C, copper, and magnesium help it function better and lower histamine through optimizing clearance.
· Quercetin & Nettles: These natural antihistamines stabilise mast cells. Found in apples, onions, berries, or taken in a supplemental formula, they reduce histamine release and support gut-immune balance.
· Omega-3s: Anti-inflammatory fats from wild fish, flax, or chia seeds help modulate immune responses and reduce the prostaglandins linked to menstrual pain and mood swings.
· Probiotic Strategy: Some probiotic strains (like Lactobacillus rhamnosus) may help with histamine metabolism, but others can worsen it. Tailored microbiome support matters and I can help you with this strategy.
Foods to include at key stages of your cycle:
· Menstrual Phase (Days 1–5): When inflammation is highest. Focus on foods that lower inflammation but that are not high in histamine: like fresh pears, cucumber, courgettes, sweet potatoes, chia seeds, ginger, carrots, broccoli and fresh apples and optimise hydration (1.5 -2 Litres of fresh filtered water per day)
· Follicular Phase (Days 6–14): As oestrogen rises aim to support your detox pathways with sulphur-rich foods (garlic, onions, eggs) and lots of vitamin c rich foods but which, again, are lower in histamine including: broccoli, cauliflower, cabbage, kiwi, papaya, mango. The cruciferous veg (like broccoli, cauli, cabbage etc.) also help optimise liver detoxification.
· Ovulation (Day 14): as oestrogen peaks, and histamine surges -include foods that help histamine breakdown. Prioritise fresh, unprocessed foods like vegetables (excluding tomato, aubergine and spinach), certain fruits (non-citrus), and fresh meat and fish. Consider including foods that are good sources of diamine oxidase (DAO) too, like bean sprouts, which helps break down histamine.
· Luteal Phase (Days 15–28): As progesterone rises, include vitamin B6 and magnesium rich foods (spinach, sweet potato, pumpkin, bananas, courgettes and carrots) alongside calming practices like breathwork, yoga or vagal nerve stimulation which can be additionally very helpful.
Other key functional strategies:
Liver Detoxification: As mentioned above, your liver breaks down oestrogen. And cruciferous veggies can be helpful alongside bitter greens, and herbs like dandelion root or milk thistle.
Blood Sugar Stability: Fluctuating blood sugar worsens hormonal and histamine sensitivity. I always suggest you focus on protein packed meals, adequate fibre intake, and healthy fats to keep glucose steady through your day. I often add in blood sugar balancing support with supplements like chromium, berberine and alpha lipoic acid. But these should be monitored carefully as for some they may lower blood sugar too far and cause another set of unhelpful symptoms.
Adrenal Support: Chronic stress disrupts progesterone balance and raises histamine. I love using adaptogens like ashwagndha, rhodiola or holy basil (only with guidance) to calm the HPA axis.
Self tracking strategies and cycle mapping:
Logging symptoms, food, medication, and emotional states across your cycle can reveal patterns and support more effective care decisions. Tracking apps or simple journals can offer useful insights over time (7). Use your menstrual cycle as a guide. Anticipate symptom flares by tracking your physical and emotional patterns throughout the month. Stock essential supplies, schedule rest, and plan challenging tasks for more stable phases.
Functional Lab testing that may help clarify what’s going on:
I am well versed in some key functional testing to uncover YOUR root causes and areas of imbalance:
Dutch Hormone Panel: Measures oestrogen/progesterone metabolism and cortisol imbalances as well as uncovering neurotransmitter and nutrient deficiencies htat could be contributing to, or worsening, symptoms
Histamine & DAO levels: To evaluate histamine breakdown capacity.
Comprehensive Stool Test: Assesses gut health, which is key for hormone and immune regulation as well as assessing bacterial and yeast overgrowths that can drive higher histamine levels.
Nutrient Panels: Especially B6, magnesium, zinc, and vitamin C.
Organic acid testing: can be helpful in understanding and addressing certain aspects of both neurodivergence, like ADHD, and Premenstrual Dysphoric Disorder (PMDD). OAT analyses urine for metabolic markers, providing insights into mitochondrial function, neurotransmitter imbalances, gut health, and nutrient deficiencies, all of which can be relevant to both presentations.
Gentle Movement and Regulation
Lastly safe movement is essential, but all exercise must be approached carefully in hypermobile bodies.
I always stress how important it is to work with a trained specialist in Hypermobility or EDS. Some techniques involve:
Joint-safe dynamic mobility
Breathing techniques to calm the autonomic nervous system
Movements designed to activate the parasympathetic response, reduce stress, and minimize post-exertional flares
Even a few minutes of intentional movement or deep breathing can be beneficial on difficult days.
Final thoughts
Symptoms associated with PMDD, MCAS, ADHD, autism, and EDS/HSD are frequently dismissed, misdiagnosed, or treated in isolation. Yet, many people with these conditions, report a shared experience: their bodies seem to overreact to everything, from hormones and foods to stress and movement.
Recognizing the biological intersections among these diagnoses is a first step toward better care. Awareness leads to more precise diagnosis, and from there, more targeted, effective treatment
It’s not in your head.. the link is there and becoming more recognised.
When PMDD, EDS/HSD, MCAS, and neurodivergence overlap, the immune system, hormones, neurotransmitters, and connective tissue are all speaking the same language. A functional medicine and nutritional approach recognises these links and empowers you to address the root causes, not just mask the troubling symptoms.
If you’ve felt dismissed, overwhelmed, or invisible in your experience – or if this is the first time you’ve realised there are links - know that there are strategies that work with your body, not against it. Get in touch for support.
References:
1. Premenstrual syndrome and premenstrual dysphoric disorder: definitions and diagnosis
3. PMDD, Autism, and ADHD: The Hushed Comorbidity
4. Histamine, Hormones and Hypersensitivity
6. PMDD, Histamine, and Mast Cells: Exploring New Avenues for Treatment
7. Mast Cell Activation Syndrome: Tools for Diagnosis and Differential Diagnosis