The Hidden in Plain Sight Cause of Adrenal Fatigue

Estrogen's role in adrenal fatigue 

When we were deep in a perimenopause meltdown and running through about 4 different doctors, invariably the term "adrenal fatigue" was thrown at us.


Sounds very technical and feels so right.


But is it?


It's all the rage with the naturopath set for women in their 40's and 50's.


That alone should be a big clue!


The recommended treatment for this is a slew of supplements including adrenal material from pigs.


We'll explain why this can be a nightmare for the very women it's meant to help below.


More importantly...we'll look at estrogen.


The key driver of perimenopause is a flux and drop of estrogen.


Wait till you see why this is important for the adrenals.


Estrogen isn't the only agent here...progesterone is no slouch and we'll see why below.


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Here are the areas we'll cover based on research: 

  • A quick intro the adrenal glands and so-called adrenal fatigue
  • Why estrogen is important for adrenal fatigue
  • Why progesterone is important for adrenal fatigue
  • Other key supporters of healthy adrenal function
  • Final notes on estrogen and progesterone supplementation safety


Let's get started before some other poor women gets a bottle of bovine adrenal cortex tissue.

A quick intro the adrenal glands and so-called adrenal fatigue 

The adrenal gland is a fascinating little power-player in our hormone system.


We'll focus on three main outputs from it: 

  • Cortisol - our primary stress hormone
  • Androgens - the precursor to steroidal hormones like estrogen and progesterone
  • Catecholamines - adrenaline and the fight or flight messengers


Sure, there are other players in blood pressure and immune suppression (hello, autoimmune) but we want to focus on adrenal fatigue.


This isn't really an approved diagnosis.  


We're far from big supporters of the traditional medical field after our run-in with perimenopause and a sea of benzos and SSRIs which almost took our founder out but adrenal fatigue might be a big mistake on the naturopath side.


Essentially, adrenal fatigue is used as a catch-all diagnosis for a range of different issues per Mayo clinic: 

  • Fatigue
  • Body aches
  • Unexplained weight loss
  • Low blood pressure
  • Lightheadedness
  • Loss of body hair
  • Skin discoloration (hyperpigmentation)
  • The basic framework is that stress leads to the exhaustion of adrenal function since it makes cortisol, our primary stress hormone.


The tricky part is that this is typically foisted upon women around perimenopause when hormones are in flux.


We can get a hormone panel such as the Dutch Test to show both hormones and cortisol over a 24 hour period but that still doesn't explain the root cause.


Let's now dive into the hormone piece since we know for certain that they are in play during this time.


We'll start with the star of the show….estrogen.

Why estrogen is important for adrenal fatigue 

We covered quite a bit on estrogen already such as it's tied to mental health (here) and the new studies on supplementation safety (here).


There's also a massive review of perimenopause which is key to estrogen.


During this time (mid to late '40s), estrogen starts to go on a roller coaster ride after which it plummets leading into our 50's (on average).


Estrogen is a major player in every pathway of your body: 

  • Heart
  • Brain
  • Blood
  • Bone
  • Organs


You name it...there are estrogen receptors there.  Check out the mental health review to learn how it supports a healthy brain and nervous system.


Serotonin affects alone should warrant the read.  It's the master regulator of mood and all human behavior.


Yes, estrogen is tasked with supporting it in the female body and brain.


See CBD and serotonin to learn more.


What happens when a major support base starts to leave the scene as the ovaries stop producing estrogen?


The body panics!


There's only one other place to manufacture estrogen internally in the body.


Guess where that spot is….


The adrenals!


First the technical: 

Observations over the past decade using longitudinal data reveal a gender-specific shift in adrenal steroid production. This shift is represented by an increase in the circulating concentrations of delta 5 steroids in 85% of all women and is initiated only after the menopausal transition has begun.


Essentially, the adrenals ramp up to make up for steroidal hormone production ramping down in the ovaries.


These experimental results support the concept that LHRs are recruited to the adrenal cortices of mid-aged women that subsequently function to respond to increasing circulating LH to shunt pregnenolone metabolites towards the delta 5 pathway. 


The adrenals then become the focus of steroidal hormone creation as a stop-gap mechanism.


Goodness...the body is frantically trying chemistry workarounds to get to estrogen and progesterone.


This is a big misconception in our entire healthcare system.


Estrogen and progesterone are just for reproduction




They govern every pathway in the body.


Progesterone and estrogen literally shape the heartbeat rhythm on the front and back end.




Mother Nature is ruthlessly efficient.  She will take an existing pathway and piggyback it for many other uses. 


For example, the COX2 pain pathway that Ibuprofen and NSAIDs manage also helps govern heart and gut function.


Hence, the side effects there for longer-term use (see CBD versus antiinflammatories or CBD versus Tylenol).


Estrogen has powerful effects across the body and brain both from replenishing and growth aspects as well as maintenance.


Let's give just one powerful example.




It's our master mood regulator and basically the manager of all human behavior (see CBD and serotonin).


Estrogen directly drives serotonin in the brain: 

Estradiol is especially nurturing towards serotonin – it stimulates TRPH expression to ensure that enough serotonin is made and suppresses MAO A levels to prolong the longevity of the neurotransmitter. boosts its creation from tryptophan (TRPH) and slows its removal (MAO).


This is the linchpin for depression, anxiety, sleep, mood issues, pain, and just about every mental health issue.


In fact, the most common antidepressants boost serotonin (See CBD versus SSRIs) till they start building tolerance.


More importantly, there's a downstream pathway driven by serotonin called BDNF.


BDNF is your brain's fertilizer and it's probably the most powerful mental health player you've never heard of (see CBD and BDNF or CBD and brain repair).


A study looked at the most telling triggers of relapse with addiction and they were: 

  • Stress (serotonin is a stress buffer)
  • BDNF levels 


This should be front-page news!


In fact, the brain benefits of exercise, meditation/yoga, and psilocybin can all be partially given to BDNF.


So...estrogen goes into extreme fluctuations around the mid to late 40s and then plummets.


No wonder the body panics and reroutes estrogen production to of the few places it can still make estrogen.


With such a high demand (high priority) demand on production, no wonder adrenals are exhausted and other key players go awry: 

  • Low cortisol - fatigue, lethargy
  • Low aldosterone - blood pressure
  • Low adrenaline - brain fog, fatigue, low mood

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It's not just estrogen which is more sudden (late 40's).

What about progesterone 

We mentioned before that adrenal glands need to take over "steroidal hormones" which means the entire panoply of players.


This includes progesterone: 

Progesterone is produced in gonads, adrenal cortex, and also in the brain in both males and females.


Remember that the ovaries (gonads in females) are closing shop with perimenopause.


Interestingly, progesterone has a completely different trajectory than estrogen.


It starts dropping right after our early 20's much like testosterone for men.


In fact, progesterone has likely dropped by 50% at age 40!


That's fine though right?  We just need it for making babies.




Progesterone is just as important as estrogen across almost every pathway.


We'll look at just two powerful aspects.


First, progesterone calms the immune system when it's too strong.


This speaks to the constant ramp-up of autoimmune that hit women 8/10 times compared to men.


See CBD and autoimmune.


Keep in mind that autoimmune is THE disease of the day in places you might not think (see CBD and dementia).


It's fascinating as to why progesterone has this effect.


The amniotic sac is actually made by the father's DNA.  Because of this, there's a danger that the mother's immune system will see it as a foreign entity and attack it.


Progesterone spikes up during pregnancy and it calms this response.


In fact, recent research tied low progesterone to premature births and other complications.


Secondly, let's turn to the brain and nervous system.


There's a powerful metabolite of progesterone called allopregnanolone which directly boosts and manages GABA.


GABA is the brain's "brake pedal" and it's the direct target of benzos like valium, Xanax, and Ativan.  See CBD and GABA or CBD versus benzos.


GABA is critical for sleep, calm (anti-anxiety), depression, brain health, and pain.


It's very common that anxiety, depression, pain issues like fibromyalgia all creep up with women during their 40's.


A synthetic version of the allopregnanolone is the new blockbuster postpartum (drop-in progesterone) drug.


Pregnenolone is a cheap supplement that supports this powerful metabolite.


A brand new study showed that reduced levels of progesterone earlier in life are tied to more severe perimenopause transitions.


In fact, it acted like a stress-response buffer with protection from depression as well.


A chronically stressed brain quickly becomes a depressed brain.


On a side note, alcohol boosts both GABA and serotonin until tolerance actually makes it worse.


No wonder so many women are drinking into their 40's.


See CBD versus alcohol to learn more.


Back to the adrenals...sorry for the detours.

Why progesterone is important for adrenal fatigue 

Most of the symptoms tied to adrenal fatigue don't just smack us at 48 with the onset of perimenopause.


There's a slow creep of pain, inflammation, histamine response, and more.


Remember that progesterone starts dropping much earlier and just keeps going down.


50% by age 40.


So the adrenal gland production is slowly being diverted to progesterone and then gets slammed by the drop in estradiol.


And remember: 

Since the adrenal glands “take over” sex hormone production postmenopausally, holistic treatment for menopausal symptoms necessitates optimizing adrenal gland function


To that end...

Other key supporters of healthy adrenal function 

Let's start with our own anecdotal story.


When the founder first started taking the Dutch test, our cortisol cycle was totally upside down.


It peaked in the middle of the night around 4 am, was low in the morning, and trailed off during the day.


Naturally, there's a little bump around 4 am which is why many people get up.


It should spike in the morning to get us moving.


The trail off during the day matches a slow exhaustion.


With the addition of progesterone and estrogen supplementation (see details here and here), this cortisol response fell back in line!


This is fascinating since we only changed the hormone makeup.


As a side note, we bounced between the estradiol gel versus cream plus the location which always causes a drop in estrogen absorption temporarily.


As a result, the Dutch test showed some issues in the 24-hour cortisol response (really trails off as the day goes on).


Once the estrogen was corrected, it came back in line.


These systems are all interwoven and highly complicated but steroidal hormone support is critical.


We had to research and fight our way to get bioidentical hormones (see topical versus oral estradiol).


A new study on Bijuva leads the fight against the horrible precedent set in 2001 by the WHI study.


In addition, there are critical components needed for adrenal function: 

  • Vitamin B's - critical to adrenal function
  • Magnesium Threonate or glycinate 


Look at Vitamin B effects under stress: 

Improvement of the enzyme system in adrenal glands in animals through swimming training with addition of vitamins B1, B6 and B12 leads to faster and long-term production of hormones necessary for stress response known as General Adaptation Syndrome


Research is here:


Then there's mag (see our big magnesium review for mental health here): 

Magnesium also acts at both the pituitary and adrenal levels. In the pituitary gland, it modulates the release of ACTH, a hormone that travels to the adrenal glands, stimulating cortisol release. In the adrenal gland, it maintains a healthy response to ACTH, keeping cortisol release within a normal range.


In the end, there's no substitute for estradiol and progesterone to alieve this workaround on the adrenal glands and correct the cortisol imbalance.


If you need just one of many examples, look at estrogen's role with blood pressure and cardiovascular health: 

The cessation of endogenous estrogen production contribute to a raise in BP,2,6 thereby increasing the risk of hypertension, atherosclerotic vascular disease, myocardial infarction, and stroke.


Goodness...when estrogen goes down, the entire cardiovascular complex deteriorates.


Now...if you go into a doctor's office asking for hormone replacement therapy, they'll warn you that it might cause a stroke.




Let's go there now.

Final notes on estrogen and progesterone supplementation safety 

We've covered this in detail (for our own curiosity and safety) here: 

  • Estradiol supplementation safety history
  • Topical versus oral estrogen update


Here's the rub….decades of research show nasty results from…


Synthetic hormones!


There's a clearly different risk profile between bioidentical and synthetic.


It's all over NIH research but the hormone replacement studies are based on synthetics.


Read the reviews.


The fact that we had to wait for the Bijuva studies to get a clear representation with robust FDA clinical requirements for bioidentical estradiol and progesterone this late in the game (2019) is infuriating.


Check out the Bijuva safety studies review here.


For two decades, millions of women were just left out to dry.




Find a naturopath or doctor who is up to speed (very few from our experience) and bring research with you.


When "adrenal fatigue" invariably comes up (more on the naturopath side), you'll be better versed now.


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Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.


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