Cortisol, often referred to as the “stress hormone”, has been given a bad rap over the last few years. Everywhere you look, there’s information talking about the link between high cortisol and inflammation, cortisol and belly fat, and cortisol and anxiety.
Meanwhile, the supplement industry is abounding with products meant to reduce cortisol production and calm your nervous system in doing so.
And yet, I tend to see symptoms and biomarkers of adrenal hypofunction and low cortisol far more often than I see them high. This is across both genders, but especially in women. And these people are anything but tranquil and calm. They tend to experience anxiety, sleep disturbances, constant fatigue, brain fog, and a lower sex drive. They are also the women experiencing the greatest burden of disease, often with reduced capacity for work, caregiving activities, and loss of function in daily life.
What I see in clinic aligns with what’s seen in the literature. Several conditions disproportionately affect women and have been associated with hypocortisolism. These include fibromyalgia, chronic fatigue syndrome, chronic pelvic pain, and post-traumatic stress (PTS; I have deliberately left the disorder off the name here, because I think a trauma response is anything but disordered). The trauma research here is particularly interesting: a recent line of work on trauma exposure found that childhood trauma predicts blunted cortisol reactivity in women but not in men exposed to the same trauma. Same stressor, sex-specific outcome, suggesting something about female HPA-axis regulation itself responds to chronic/early stress by going quiet rather than staying loud.
This doesn’t give us exact numbers on who is affected most by hypocortisolism, but we can infer from this work that women are disproportionately impacted.
Why hypocortisolism is more common in women
So, why are women struggling more with hypocortisolism?
Possibly something to do with sex-specific biology.
Estrogen and progesterone pull in different directions on HPA-axis regulation. Estrogen, acting through estrogen receptor alpha, tends to increase HPA responsiveness — which on its own would predict women have more reactive, not less reactive, cortisol output. Progesterone complicates that: it reduces glucocorticoid receptor sensitivity, meaning that even when cortisol is produced, the tissues respond to it less efficiently. Women in the luteal phase specifically show reduced glucocorticoid sensitivity alongside increased inflammatory cytokine production, a pattern that looks a lot like glucocorticoid resistance. The same amount of cortisol is doing less work for you.
Androgens are the other side of it: testosterone and DHT actively suppress HPA-axis reactivity in men. Women, with far less circulating androgen, don’t get that same brake — which should, in theory, make women’s stress response more reactive, not less. That’s part of why this area is genuinely unresolved: some sex-hormone mechanisms point toward women being more reactive, while the receptor-sensitivity and feedback-efficiency mechanisms point toward women being more prone to the blunted, resistant pattern once stress becomes chronic.
The honest read is that acute stress reactivity and chronic hypocortisolism may be governed by different parts of this system, and the sex-hormone literature has mapped the acute side more thoroughly than the chronic one. This likely explains some of what I see in clinic, because the people I work with are generally dealing with chronic conditions, not coming in for acute issues.
There’s also a non-hormonal piece worth considering: women are disproportionately exposed to some of the chronic and interpersonal stress exposures most strongly linked to hypocortisolism later on, including childhood sexual trauma, which shows up repeatedly in the trauma-and-blunted-cortisol literature. It also shows up a lot in my clinic, whether I’m doing therapy with a client or not. That’s an epidemiological/social explanation sitting alongside the biological ones, not a competing one. The effects compound with those related to gender-derived biochemistry.
What cortisol is for
While it’s true that cortisol is linked with stress, its role in anxiety and mental health is badly misunderstood in popular culture and even amongst many health professionals. The dominant model treats chronic stress as a problem of too much cortisol. It’s worth mentioning here that women were largely excluded from the development of this model - it is built predominantly on research in men. A growing body of evidence shows that hypocortisolism and glucocorticoid resistance (cells becoming less responsive to the cortisol that is present, measurable via dexamethasone suppression testing) produce their own distinct pathology. For example, Raison and Miller published a review article in 2003 describing impaired feedback control over immune activation and inflammation in stress-related neuropsychiatric disorders.
The main mechanism that links how we feel to immune activity runs through the coordinated action of catecholamines and cortisol. Noradrenaline and adrenaline fire fast, switching on an inflammatory response that, left unchecked, runs hot. Cortisol arrives to apply the brakes, not to shut inflammation down but to cap it, and all three hormones are needed to bring inflammation to resolution once its job is done. Lose the brake, and inflammation runs longer than it needs to.
So, not only is the idea that high cortisol is the outcome or reason for high stress levels a misnomer and largely based on research not taking women’s biology into account, but the idea that suppressing cortisol is somehow going to fix things is also false.
The surprising pattern in endometriosis
I had already been thinking about misperceptions around cortisol after a recent conversation with a client, but this week it moved front and centre when I was doing a deep-dive on the endometriosis literature.
A 2008 study by Petrelluzzi, Garcia, Petta, Grassi-Kassisse & Spadari-Bratfisch, published in the journal Stress, called “Salivary cortisol concentrations, stress and quality of life in women with endometriosis and chronic pelvic pain” brought what I was seeing a lot of in clinic into focus. The researchers found that women with endometriosis and chronic pelvic pain showed markedly lower salivary cortisol across all three sampling points in the day, plus a blunted cortisol awakening response, alongside high perceived stress and poor quality of life. To be specific, the average awakening cortisol was around 0.19 μg/dL in the endometriosis group versus 0.78 μg/dL in controls. That’s almost four times lower in the endometriosis cohort.
A second, complementary finding comes in the form of a study in Fertility and Sterility that found that among women with endometriosis, those who also met criteria for chronic fatigue syndrome had higher psychological stress and lower cortisol than those without CFS. This suggests the hypocortisolism isn’t incidental but tracks quite neatly with symptom burden.
A separate line of intervention evidence is worth a mention too. Petrelluzzi’s own follow-up work found that physical therapy and psychological intervention normalised cortisol levels and improved vitality in women with endometriosis. This doesn’t mean nervous system work and exercise are going to fix everything in women with endometriosis, but it does indicate that they can be a solid starting point.
The pattern repeats
This is where things get really interesting. In their 2005 review article, Fries, Hesse, Hellhammer & Hellhammer named this as a recognised cluster: hypocortisolism appears in roughly 20–25% of patients with chronic fatigue syndrome, chronic pelvic pain, fibromyalgia, PTSD, irritable bowel syndrome, chronic low back pain, burnout, and atypical depression — unified by a triad of heightened stress sensitivity, pain, and fatigue. Nearly every one of those is female-predominant or substantially female-skewed.
Fries et al. also propose that hypocortisolism likely develops as a downstream adaptation after a period of HPA-axis hyperactivity under chronic stress. In essence, the system turns its own volume down rather than staying permanently loud. That’s where glucocorticoid receptor desensitisation fits: it’s actually your body trying to adjust to its new normal.
The other thing that I see, though, is an outright inability to produce cortisol. Looking back over a month’s worth of testing recently, I noted that at least 50% of the women I had tested for vitamin C were outright deficient, by which I mean they were below the (very broad) lab range. A small handful of these were so low that they were flagged at risk of scurvy. Around another 35% were sub-optimal. Only a few had vitamin C in the optimal reference range. This isn’t published data and it’s important that I acknowledge it’s from a very specific subset of people, all with chronic health concerns, so it can’t be taken as representative of the wider population. But it’s certainly striking enough that I now screen for vitamin C deficiency in almost every client.
Vitamin C is a required cofactor for both adrenal cortex and adrenal medulla steroidogenesis, and the adrenal cortex holds one of the highest tissue concentrations of vitamin C in the body, up to 50 times plasma levels. HPA-axis activation triggers active secretion and depletion of adrenal vitamin C, and animal studies show adrenal ascorbate stores drop within minutes of an acute stress event. Every stress response has a nutritional cost and the women I work with are paying the price of it.
I also frequently supplement pantothenic acid (B5) alongside vitamin C. It’s one of the nutrients that’s impossible to test unless running an Organic Acids Test (OAT), but it comes with few side effects and a solid evidence base in adrenal function. A series of 1950s–60s animal studies established that B5 deficiency causes adrenal atrophy, hemorrhage, and reduced corticosteroid output. B5 acts as the precursor to coenzyme A, which is required at the very first step of steroidogenesis (cholesterol to pregnenolone).
So two things can be happening at once: reduced ability to utilise cortisol, and reduced ability to produce it.
The clinical stakes of guessing wrong
If you take nothing else away from this article, remember this: there is a price to be paid for suppressing a system that’s already struggling to make ends meet. Taking supplements that reduce cortisol production further can make you feel even more tired, washed out, and inflamed than before if your adrenals are already struggling or your system is trying to downregulate cortisol’s effects.
This is why testing, not guessing, matters. A single morning cortisol reading tells you almost nothing about a system that’s supposed to rise and fall across the day; four-point salivary testing (or a DUTCH test, which adds metabolite detail) shows you the actual rhythm and whether the problem is low output, a blunted awakening response, or poor clearance. Pair that with nutrient markers like vitamin C, and you’ve got a far more honest picture than cortisol alone.
Cortisol was never the villain of this story. It’s the thing holding the line while everything else in the system is still trying to recover. Before you reach for something that turns its volume down further, find out whether it was ever turned up to begin with. Test it. Then decide.
Want to dig deeper into your own cortisol status but don’t know where to begin? Book a free orientation call to find out more about how I can support you in moving forward with your health.