Is It Really Menopause — Or Is It MCAS?
Photo by mojtaba mosayebzadeh on Unsplash.
Menopause has long been framed as an inevitable rite of passage for women in midlife: a period of hormonal adjustment marked by symptoms like hot flushes, sleep disturbances, mood swings, and weight gain. Women are often told it’s something simply to be endured.
Not so fast.
While some discomfort is to be expected as oestrogen and progesterone levels decline, the degree of suffering many women experience today often far exceeds what would have been considered ‘normal’ in previous generations.
This begs an important question: are these symptoms purely hormonal — or is there something else at play?
Increasingly, evidence suggests that for a significant number of women, the distress attributed to menopause may in fact reflect an underlying condition that dysregulates the immune, nervous, and endocrine systems: mast cell activation syndrome (MCAS).
While mast cells play an essential role in immune defence and tissue repair, in MCAS they become hypersensitive and prone to inappropriate activation, releasing histamine, prostaglandins, cytokines, and other mediators that trigger widespread symptoms (Afrin et al., 2016). For many women, this destabilisation coincides with perimenopause and menopause, creating a perfect storm where declining sex hormones reduce mast cell stability just as sensitivity to histamine and inflammatory mediators peaks.
In this post, I’m going to explore how MCAS can mimic — and magnify — menopausal symptoms, and why it's time we reconsidered how we assess and treat women in midlife.
Modern Lifestyles Increase Menopause Severity
I often hear from clients that they’ve had or are having a terrible time with menopause. Terrible sleep, fatigue, aches and pains, anxiety and mood swings, excessive weight gain, flare-ups of any skin issues - these are all symptoms that I hear about constantly.
And yes, menopause is a period of major change, so it should be expected to come with some changes. But not to the extent that most women are experiencing.
“Because hunter-gatherers are extremely vigorous and active even through the late menopause years, they are likely to have been among the least bothered by menopausal symptoms, as evidenced by data on sleep disorders in women from less developed nations as compared with sedentary women in post-industrial countries.”
Night-time wakings are considered a good marker of vasomotor symptoms associated with menopause. The better you sleep during menopausal years, the less affected you’re thought to be by the menopause process. What these researchers are saying is that the severity of the symptoms experienced in places like the US and Australia is abnormal, which they attribute to a more sedentary lifestyle.
That makes it sounds really simple - just get outside or into the gym and do some exercise.
But what if you’re active and still experience severe menopausal symptoms?
Clearly, there are other factors at play.
Hormone Shifts and Mast Cell Sensitivity
Oestrogen and progesterone aren’t just reproductive hormones — they also regulate mast cell activity. Oestrogen, in particular, has a biphasic effect: in low concentrations, it can stabilise mast cells, while in higher concentrations it can increase mast cell degranulation. Progesterone, by contrast, tends to act as a mast cell stabiliser.
As women transition through perimenopause and into menopause, oestrogen levels fluctuate. Meanwhile, progesterone falls progressively, in a more constant fashion. This means you can feel fine one day because oestrogen and progesterone are in relative balance, stabilising mast cells. Then oestrogen might spike or fall dramatically, putting everything out of balance. This increases the release of histamine and inflammatory mediators, amplifying symptoms traditionally ascribed to menopause.
The issue is further complicated by the fact that mast cells themselves express oestrogen receptors (ERα and ERβ) and progesterone receptors, meaning they directly respond to changing hormone levels. This makes the menopausal period a particularly vulnerable time for the activation or exacerbation of MCAS.
Histamine, Menopause Symptoms, and MCAS
Many of the symptoms attributed to menopause mirror those of histamine intolerance or MCAS, including:
Hot flushes and night sweats: Histamine is a potent vasodilator and thermoregulatory agent. Excess histamine can cause sudden vasodilation, leading to the classic heat surges associated with hot flushes.
Sleep disturbances: Histamine acts as a neurotransmitter involved in wakefulness. Elevated histamine, especially overnight, can disrupt sleep architecture and reduce sleep quality.
Anxiety and mood swings: Histamine crosses the blood–brain barrier and modulates neurotransmitters including serotonin, dopamine, and GABA. Elevated levels can drive anxiety, irritability, and depressive symptoms.
Migraines and headaches: Histamine-induced vasodilation of cerebral vessels is a well-documented migraine trigger, which worsens during hormonal fluctuations.
Palpitations: Histamine acts on cardiac H1 and H2 receptors, increasing heart rate and contributing to palpitations and tachycardia.
Brain fog: Neuroinflammation driven by mast cell mediators can impair cognitive function, manifesting as memory lapses and poor concentration.
Weight gain, gastrointestinal symptoms, joint pain, and skin rashes — all commonly attributed to menopause — are also classic features of MCAS. This overlap often means MCAS remains underdiagnosed, its symptoms dismissed as part and parcel of midlife hormonal changes.
Is It More Than Menopause? Red Flags for MCAS
Now, all of this isn’t to say that hormonal changes don’t play a role in the menopausal transition. They clearly do, which is why hormone replacement therapy can be so helpful in controlling symptoms.
But when symptoms are severe, resistant to conventional treatments, or accompanied by a history of atopy, food sensitivities, chemical intolerances, or unexplained systemic symptoms, I strongly believe that MCAS should be considered.
Key features suggestive of an underlying mast cell issue include:
A history of cyclical symptom worsening around ovulation and menstruation (when oestrogen peaks).
Heat intolerance and flushing triggered by foods, stress, alcohol, or exertion.
Persistent or multiple unexplained symptoms across different systems (e.g., gut, skin, nervous system).
Poor tolerance of hormone replacement therapy (HRT) or worsening of symptoms on certain formulations.
It’s worth noting that while menopause can destabilise mast cells, women with a lifelong but subclinical tendency towards mast cell hyperreactivity may only become overtly symptomatic during this period of endocrine transition.
Emerging Research: Mast Cells, Oestrogen, and Menopausal Disorders
Recent studies underscore the complex interplay between mast cells and sex hormones. A 2019 study published in Frontiers in Cell Neuroscience highlighted how declining oestrogen may lead to increased mast cell degranulation in brain regions responsible for thermoregulation, contributing to vasomotor symptoms.
Additionally, animal models have shown that blocking mast cell mediators can attenuate hot flushes and anxiety-like behaviours in oestrogen-depleted states.
And in one of the most fascinating studies of all (though I feel for the rats in this one), female rats with asthma were found to experience less airway inflammation once their ovaries were removed. Overactive mast cells (as seen in MCAS) play a leading role in asthma and airway inflammation, so when oestrogen production was reduced through ovary removal, so did airway inflammation. Moreover, when the ovariectomised rats were given HRT to replenish oestrogen, their airway inflammation increased once more.
These findings support the idea that mast cell dysregulation is not merely a side effect of menopause but may be a driving factor in the severity and breadth of symptoms many women experience.
Putting This Into Practice
If you’re navigating menopause and struggling to get relief from your symptoms, understanding how MCAS might be playing a role could be life-changing. This is especially true if you’ve tried HRT to no or little avail. For many of you, addressing the MCAS itself may be a better path towards relief from symptoms.
Understanding the bi-directional relationship between the endocrine, immune, and nervous systems is crucial as part of this. Mast cells interface with all three, which means that addressing one system in isolation is unlikely to resolve the broader pattern of dysfunction. As such, all three often need to be addressed synergistically to really move the dial.
There are multiple ways of doing this, and no two people are exactly the same. This means that, while principles like minimising oxidative and reductive stress whilst optimising mitochondrial function hold true for everyone, there’s no one best way of tackling this issue. It requires a nuanced and reflexive approach - one that takes your personal context, goals, and preferences into account.
One thing is for certain, though.
It’s time to move beyond the narrative that debilitating symptoms are a normal part of ageing — and start asking whether it’s really menopause, or if it’s MCAS.