Estrogen Dominance, Interstitial Cystitis, and Adrenal Fatigue
The hidden link between estrogen dominance, interstitial cystitis, and adrenal fatigue
This post is for you if you have high estrogen levels and either suspect (or know) your cortisol levels are tanked.
This is also your article if you've been told your labs are "normal" and yet, you’re struggling with a laundry list of mystery symptoms: IC/chronic UTI, brain fog, inflammation and that "raw" histamine-y feeling (MCAS), bladder trouble, gut trouble, autoimmune, and yes even erratic blood pressure.
There are a few ways to define estrogen dominance:
Estrogen is high compared to progesterone.
Estrogen is high.
We're focusing on that second definition here. You already know your ovaries make estrogen, so it makes no sense now that you're "perimenopausal" for estrogen to be so high when your ovaries are "winding down reproductive capacity" or whatever the doc said.
Here's what you haven't been told... the adrenal glands (one sits atop each kidney) also make estrogen.
Low cortisol and estrogen dominance
Whether we call it adrenal fatigue or low cortisol, when the adrenals lose their ability to keep up with the brain's demand for cortisol, the adrenals still receive the signal to make cortisol. That signal isn't unique for cortisol alone though. Let's take a big step back and look at the HPA axis really quick.
The hormones of the hypothalamus-pituitary-adrenal (HPA) axis
Every hormone axis (or hormone loop) in the body starts at central command, which is the hypothalamus a gland seated within the brain. The hypothalamus itself is deeply reliant on inputs from the executive brain (pre-frontal cortex), the limbic brain (emotional brain), and the survival brain (lower brain) and also the optic nerve. The hypothalamus interprets and integrates the signals to determine which hormones to ramp up and which to ramp down.
To trigger the adrenals to release cortisol, the hypothalamus secretes the hormone CRH (corticotropin-releasing hormone). CRH is interpreted by the pituitary gland (another gland in the brain) and the pituitary secretes its own hormone, ACTH (Adrenocorticotropic Hormone). ACTH is interpreted by the adrenals.
The adrenals don't read ACTH as "we need cortisol" instead, it's more like the alarm going off on Monday morning. Meaning, the adrenals don't just stretch and yawn and look out the window before getting out of bed to start the day at a leisurely pace, they hit the ground with both feet and start multi-tasking immediately. Releasing cortisol, DHEA and other androgens, aldosterone (part of the set of hormones that help regulate blood pressure... a separate hormone axis, the RAAS is the main driver for aldosterone, but it's important to know (especially if you're dealing with dysregulated blood pressure) that ACTH has a role in regulating blood pressure too)).
Whether you ascribe to the term "adrenal fatigue" or not, there's a very real scenario where cortisol rhythm gets dysregulated. And, whether cortisol is chronically high, chronically low, or chronically dysregulated all hugely impact this delicate hormone axis.
Usually, clients I work with struggle with either chronically low cortisol or a dysregulated cortisol rhythm (which often results in inflammation after breakfast/earlier in the day, insomnia at night, or waking at 2 am and peeing like a race horse in addition to whatever big symptom cluster you're dealing with... IC/chronic UTI symptoms, MCAS, etc.).
What's interesting is... the DHEA released by the adrenals can be converted into estrogen by other tissues of the body and when cortisol is low, the brain doesn't stop secreting CRH and ACTH. CRH is pro-inflammatory and ACTH prompts the adrenals to keep producing these other hormones even when the adrenals have lost their capacity to secrete cortisol at the levels the body needs it.
And, the particular region of the adrenals that secrete DHEA are also capable of making estrogen directly as well. This is why when I see a client with high estrogen levels, I immediately suspect low or dysregulated cortisol rhythm.
Does that mean you always have to have high estrogen to have low cortisol? No. Estrogen and cortisol are both steroid hormones which means cholesterol is the pre-cursor for both. When you don't have enough cholesterol (yes, that's possible and more common than you might think) it's possible for both estrogen and cortisol to be low.
The Biological Brownout & Mystery Symptoms
Back to the scenario of high estrogen/low or dysregulated cortisol. This adrenal-driven estrogen surge creates a "Biological Brownout" by destabilizing mast cells (creating more inflammation which has to be handled) and interferes with the Sodium-Potassium Pump.
The sodium-potassium pump is an energy driven process that maintains an electrical gradient between the outside of the cell (extracellular space) and inside of the cell (intracellular space). It supports a salt gradient with high sodium concentration outside the cell and enables glucose to enter the cell through a "backdoor transit" without the need for insulin. If you're curious about this, here's a deep dive into this topic.
When this pump slows down due to this particular biological brownout, you may experience:
The "Phantom" Flare: Your bladder nerves become hypersensitized by catecholamines (adrenaline and other inflammatory signalling molecules) and high histamine. You feel all the symptoms of a UTI/IC flare, but it’s actually an energy-depleted bladder.
Unexplained Weight Gain: Part of a body's response to any kind of energy gap and excess inflammation is to hold onto weight. The story's a little more complicated than that. When the sodium-potassium pump slows down, it also slows down a backdoor entry for glucose (blood sugar) into the cells.
Insatiable Hunger: Often in bodies struggling with low or dysregulated cortisol rhythm, insulin resistance is high. This is especially common when you're struggling with IC/chronic UTI symptoms. Slowing down the backdoor transit for glucose into cells leaves the brain begging for food and the cells of the body jittery.
If this is you, you want to read this article.
The Liver’s Role in Maintaining Blood Sugar
The liver maintains fasting glucose within a narrow range through:
Glycogenolysis (immediate release of stored glucose into the bloodstream for fuel)
Gluconeogenesis (generating glucose from lactate, amino acids, glycerol)
Cortisol prompts the liver to release glucose between meals so that the entire body (all the cells of the body) has sufficient fuel (in case you've never been told this, glucose is the body’s preferred fuel source and some cells of the body, like red blood cells can only meet energy requirements using glucose... they aren't capable of making energy from fats or protein).
You may have heard about the insulin resistance → insulin sensitive spectrum. What might be new for you is the term cortisol resistance.
Just as cells can become resistant to the effects of insulin (if insulin is a key, the door lock on the cells get a bit rusty in insulin resistant states so the key doesn’t work as effectively at unlocking the door to allow glucose inside), liver (and other cells of the body) can become resistant to cortisol.
We’ll talk about this more further down this post, first, I want to lay the foundation for how this impacts energy/metabolism. And, let me just reiterate, chronic UTIs/UTI symptoms and IC flares are symptoms of a body in energy crisis (unable to meet energy demands effectively/low energy state). In this state:
Mitochondrial output drops (feeding the low energy state)
Liver glycogen stores run low (feeding the low energy state)
Glucocorticoid Receptors on cells become inefficient (leading to that insulin resistant state as those receptors aren’t responding readily to insulin like they’re made to → fueling that energy gap)
Tissues become desensitized to cortisol (cortisol resistance)
In this state, the body shifts energy conversion to alternate fuel sources leaning more heavily on:
Fatty acid oxidation
Ketone production
Amino acid–driven gluconeogenesis (catabolic, breaking down proteins)
The problem is: immune cells, urothelial (bladder) cells, the nervous system, and the brain rely heavily on glucose for stable function. In fact, next to red blood cells, the bladder lining is one of the most glucose dependent cell types in the body.
When glucose delivery becomes unreliable:
Catecholamines (basically adrenaline and other pro-inflammatory compounds) rise to compensate.
It’s worth noting that catecholamines (adrenaline) increase the permeability of the bladder wall. So, it's a double whammy: the nerves are hypersensitized by these compounds, and the barrier is physically weaker due to low ATP.Mast cell stability weakens (mast cells tend to activate or granulate releasing histamine).
Bladder sensory nerves become hypersensitized.
AND, you feel insatiably hungry (thanks to the brain freaking out over a perceived lack of energy). In other posts, especially my post on the adrenal cocktail for MCAS and hypersensitive bodies, we discuss this more. For now, let’s focus on those first three bullets…
The result of this increased inflammation (from high histamine and catecholamines) plus a hypersensitized sensory nerve intensifies urinary urgency.
Low metabolic tone → impaired cortisol responsiveness (cortisol resistance) → unstable glucose release → increased sympathetic (fight-or-flight) tone → mast cell activation/increased catecholamines (pro-inflammatory compounds) + hypersensitized bladder sensory nerves → UTI-like flares
Putting a bow on this convo: cortisol resistance
In cortisol resistance (also known as glucocorticoid resistance), your cells become "numb" to the signals of cortisol. Even if your body is producing plenty of the hormone, the receptors on your cells aren't responding to it effectively creating an energy gap.
The energy gap induced by Cortisol Resistance
When your cells stop "hearing" cortisol, two major systems fail to function properly:
Fuel Delivery Fails (The Energy Gap): Normally, cortisol tells your liver to release glucose between meals to keep your brain and organs fueled. In a state of resistance, the liver ignores this "release" order. This leads to unstable blood sugar levels (crashing between meals).
Inflammation Goes Unchecked: Cortisol is your body’s primary "fire extinguisher" for inflammation. When your immune cells become resistant, they keep pumping out pro-inflammatory compounds (like histamine and cytokines) because cortisol isn't there to tell them to stop. This is why "phantom flares" and bladder sensitivity increase during periods of resistance.
Why Does This Happen?
Cortisol resistance is an adaptive survival mechanism caused by:
Chronic Stress Overload: If the "cortisol alarm" has been ringing for years due to chronic pain or life stress, the cells eventually downregulate (remove) their receptors to protect themselves from overstimulation.
Insulin Resistance Crosstalk: High levels of insulin can actually interfere with the cortisol receptor's ability to work. They "jam" each other's signals.
The Circadian Mismatch: If your cortisol rhythm is flat (no morning peak), the receptors never get a "rest" period, which makes them less sensitive over time.
In other words, cortisol resistance is the body's highly intelligent response to chronic stress.
But, my cortisol levels are “normal”
This is the most common comment I hear among clients (whether we’re talking cortisol, insulin, or thyroid). You might have "normal" cortisol levels on a blood test, but if your receptors are resistant, your tissues are essentially in a state of cortisol deficiency.
Your bladder nerves feel the "fire" of inflammation because the "extinguisher" (cortisol) can't get into the cell to put it out.
And, blood tests are one of the worst ways to "see" what's really going on with cortisol. A four point saliva test does a much better job of "mapping" cortisol rhythm throughout the day and picking up low, high, or dysregulated patterns.
The free method I use with my clients for tracking cortisol? Monitoring your basal body temperature (BBT), in other words, tracking what your temperature is at the start of the day.
If you'd like to know more about how to use your basal body temperature as a sign for cortisol rhythm, stay tuned to an upcoming post.
In the meantime, if you're struggling with interstitial cystitis flares or chronic UTI symptoms, book your initial consult with me here.
