Our entire story began with a brutal perimenopause (more on that here).
Around age 47, the founder started to have rolling anxiety and panic attacks.
Of course, 4-5 doctors (in succession) prescribed benzos, SSRIs, heart meds, and more during a 6 month period that landed her in the ER multiple times and almost broke her.
In the end...it was hormones.
We covered progesterone in detail here which is powerful for GABA (target for benzos) and immune support but estrogen is no slouch.
In fact, it's directly tied to our master mood regulator, serotonin.
We'll dive into that below.
We see this effect any time that estrogen is in flux:
- Monthly periods - about 3-4 days prior to the period
- Puberty - ramping up of the estrogen pathway
- Pregnancy and postpartum
- Perimenopause - downshifting and flux of estrogen
- Menopause - reduction in estrogen
On top of this, a now-disclaimed report in 2001 scared every woman and their doctor about hormones (both estrogen and progesterone) and set up a generation of women for nightmare outcomes.
We'll look at that as well plus the safety aspect which we've covered in detail here.
These are the topics we'll cover:
- Cycles of estrogen and its multi-tasking
- The estrogen and serotonin connection
- Estrogen and BDNF - our brain's fertilizer
- Estrogen is a growth factor - both good and bad
- Synthetic estrogen is not estrogen!
- Ways to protect against the growth side of estrogen
Let's get started.
Cycles of estrogen and its multi-tasking
We've written about 1M+ words on CBD research down just about every pathway you can think of.
What's fascinating with this level of analysis is how Mother Nature sure does like to multi-task.
If there's an existing pathway in use for say...reproduction...the body will also use that same pathway for a host of other things.
It's actually very efficient.
This is where everyone goes wrong with estrogen and our so-called steroidal hormones to begin with!
The lack of knowledge we discovered from the traditional medical field is nothing short of outrageous.
There's almost zero attention given to hormones and that's going to seem ridiculous once you read below.
You have millions of women going in their GP or OBGyn each year with anxiety and/or depression in their mid to late 40's.
This should be a total signal (the age alone) to look at hormones.
Instead, you'll get the "your hormones are fine for your age" and a prescription to Valium, Ativan, or Xanax (see CBD versus benzos)...
Those have a black box warning and shouldn't be used for more than 2 weeks due to tolerance and addiction.
If that doesn't work, you'll get a prescription to Lexapro, Effexor, or Prozac (see CBD versus SSRIs or how SSRIs actually work). Those work for about 30% of the people who try them and also build tolerance.
"Fine for your age" is where we're starting off on completely the wrong foot.
If estrogen and progesterone only guided reproduction, that would be fine.
They don't!
Every cell in your body has receptors for both and they're intimately tied into every system including:
- Brain function and replenishment (mood, cognitive function, mental illness, dementia, etc)
- Immune function (autoimmune, dementia, etc)
- Tissue repair and replacement (skin, hair, bones, etc)
- Heart function - progesterone and estrogen literally shape every heartbeat!
We can go and on.
Unfortunately, our genetic blueprint is from 40,000 years ago and the average person never saw perimenopause back then.
Of course, there's a huge drop at perimenopause late 40's but that's not the only fluctuation.
Puberty is the opposite side of the roller-coaster and equally upsetting.
In between, about 3-4 days before a period, both estrogen and progesterone will plummet.
Check out CBD and PMS to learn more about this. This is different from PMDD where GABA receptors become insensitive to progesterone metabolites (same article above).
We also look at the drop in hormones after delivery with postpartum depression (review here).
All these "transitions" can accompany huge swings is not only mood but mental health (especially with existing diagnosis).
So...hormones matter for mental health (and sleep and autoimmune and cancer and….)
Why?
We covered Progesterone's powerful effect on GABA, our brain's "brake" pedal here but let's focus on estrogen.
The estrogen and serotonin connection
We first need to introduce the most important player to your mood and feeling of well-being.
Serotonin.
It's basically the master regulator of all human behavior!
That's not an exaggeration. Check out our review on serotonin with just ridiculous studies.
Yes, it's directly tied into depression (we'll see why below) and anxiety but those are just the obvious examples.
- Sex - everything from desire to arousal to...yes...premature ejaculation (see more here)
- Appetite - serotonin directly manages the hormonal dance behind appetite
- Sleep - serotonin shapes the whole cycle of sleep
- Motivation via downstream effects on dopamine, our reward circuit player
- Self-esteem (see serotonin and self-esteem)
Okay...I think we just covered Maslov's hierarchy of needs.
When serotonin is too low, you see a range of different mental health issues:
- Depression
- Lack of motivation
- Low affect
- Risk-taking and addiction (see CBD and addiction)
Equally, when it's too high, you have another set of nasty effects:
- Restlessness
- Insomnia (fascinating histamine connection)
- Personality disorders
- Even suicidal or homicidal thoughts!
A good summary:
Serotonin is our body’s housekeeping chemical –it promotes feelings of well-being, hence the nickname “happiness molecule”. Serotonin also arms us against adversity, providing us with resilience.
https://www.zrtlab.com/blog/archive/impact-hormones-serotonin-depression/
Feeling comfortable in your own skin is directly tied to serotonin balance.
Okay...so what's the connection with estrogen?
So a quick understanding of the serotonin cycle.
Serotonin (called 5HT) is made from tryptophan, a common amino acid found in meat.
That's why tryptophan is a popular supplement for sleep and mood. Learn more about it here.
A key limiting player on this transformation from tryptophan to serotonin is called TRPH.
Finally, on the back end, we have a powerful chemical tied to mental health called MAO.
It breaks down neurotransmitters like serotonin.
So...estrogen's (our most potent version is called estradiol) effect?
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.
https://www.zrtlab.com/blog/archive/impact-hormones-serotonin-depression/
Goodness...estrogen works like a natural SSRI...without the nasty side-effects (and it's a cluster you-know-what. See here). It's mother nature's Prozac!
Interestingly, the system that keeps serotonin in check is the endocannabinoids system where CBD works which is why we spend so much time there.
It works like a feedback mechanism to support serotonin when low but not when high!
See CBD and depression to learn more.
Our focus though is on estrogen.
As we mentioned before, serotonin is a master regulator….but of what!
Well, one powerful downstream player is dopamine. (see our dopamine review here).
Dopamine is the key to why you get up out of bed (or don't!!).
It's a motivating neurotransmitter and also critical for addiction (see CBD and addiction).
The keynote:
A number of studies indicate that serotonin and dopamine (DA) systems interact closely at a basic neurophysiological level (Daw, Kakade, & Dayan, 2002; Kapur & Remington, 1996; Wong, Feng, & Teo, 1995), and that impairment of the serotonin system function can lead to dysregulation of the dopamine system
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612120/
So...if serotonin is out of balance (especially low), dopamine becomes dysregulated.
This is a big deal. In fact, the driving factor of schizophrenia is dopamine imbalance (too much in the striatum and too little in the prefrontal cortex).
See CBD and schizophrenia (probably one of the most powerful examples we have of this balancing effect).
Probably the most powerful downstream effect of estrogen on serotonin is a pathway you've never heard of.
You're going to want to get acquainted after finding out what it does.
BDNF!
Estrogen and BDNF - our brain's fertilizer
Simply put, BDNF is our brain's fertilizer.
Think of your brain and nervous system as an epic battle between insults and repair.
On the insult front, you have the following:
- Chronic stress
- Trauma
- Infection
- Hyperactive immune response (can be primed early in life..even in utero)
- Drugs and alcohol
- Medications
The usual list of bad actors across all mental health.
BDNF and the family of neurotrophins (see CBD and BDNF) are your main defense to repair, rebuild, and even create new pathways.
Just two examples of how powerful this is.
First, studies dug deep into how SSRIs actually work (see review here).
Essentially, they boost available serotonin but when the conversion for BDNF was blocked, the neurogenesis (brain repair) and anti-depressant effects went away!
Even with elevated serotonin!
See...serotonin directly boosts BDNF.
Another critical example with addiction.
The two most common triggers of relapse with addiction:
- Stress hormone levels
- BDNF levels!
Okay, the first one is pretty easy to see but the second?
This is a game-changer and BDNF is the key behind other powerful tools for mental health:
- Exercise. Boosts BDNF
- Mindful meditation and yoga? BDNF
- Psilocybin (magic mushrooms)? An explosion of BDNF>
We have reviews on all of those (just search at top of page).
So...to recap.
- Estrogen directly drives serotonin
- Serotonin directly drives BDNF
Class dismissed.
Really check out our review of CBD and brain repair or CBD and BDNF to learn just how powerful this is.
Our giant review of CBD and mental health shows how serotonin and BDNF are spread across the whole class.
For women, Mother Nature chose to piggyback estrogen's roles with supporting this entire pathway.
But hey...your numbers are fine for your age! Here's a Lexapro.
If you're angry by now, it's not estrogen's fault. It's the medical community's total disregard for the power of estrogen.
So...let's look at why this is common practice (in the US anyway) for women who are losing their estrogen.
Estrogen is a growth factor - both good and bad
We did a deep dive on our primary estrogen called estradiol here….primarily from a safety aspect.
Estrogen actually has two dominant receptors in the body:
- A or Alpha - generally a growth and replenish bent
- B or Beta - more of a housekeeping effect
There was a giant study in 2001 from the WHI which basically said that supplementing steroidal hormones like progesterone and estrogen would lead to blood clots and cancer.
Read our review here where we really dig into the study and those that followed.
The report has been largely debunked now and there were numerous flaws.
Newer studies looking at BIOIDENTICAL estradiol and progesterone actually show better profiles for uterine growth and clots! That's the link here.
Remember, there's a constant destruction-construction cycle going on.
You can see this with skin, hair, and bones.
One of the first things to reflect a drop in estrogen is the vitality (for lack of a better word) of this type of tissue which requires estrogen to constantly rebuild.
In fact, atrophy (a withering of tissue) is a common side effect from estrogen leaving the scene.
This is especially true in areas heavily tied to estrogen's pathway such as vaginal and urinary tracts.
We need estrogen's growth (the alpha receptor) but too much of it and that's where the cancer piece comes into effect especially if genetics come into play.
Let's go back to that the WHI study that caused millions of women to drop estrogen (and progesterone).
It was based on synthetic estrogen (estrins) and/or horse-derived estrogen (primarily Premarin).
One thing we've learned from the million+ words of research on this site is that synthetic NEVER matches the safety profile of bioidentical.
I can't believe we even need to go there but…
- Hydrogenated oil - almost killed a generation with cardiovascular issues
- Fake sugars - see our review on gut inflammation
- Progestins versus progesterone - almost opposite safety - see progesterone review
Even synthetic CBD (called Epeliodex) has a completely different side effect profile than just CBD isolate. CBD isolate is much much better on this front.
Unfortunately, most women are on synthetic hormones either via birth control or hormone replacement.
Again, we go deep into estrogen supplementation safety here. Work with your doctor or better yet, a naturopath who might actually run a Dutch test and deal with hormones.
Let's turn our attention to synthetic versus bioidentical.
Synthetic estrogen is not estrogen!
This is really important.
There's a general belief in the medical community that synthetic estrogens are just fine.
It's really just ignorance.
Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures.
https://pubmed.ncbi.nlm.nih.gov/19179815/
As for progesterone versus progestins (the primary use in birth control):
Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins
https://pubmed.ncbi.nlm.nih.gov/19179815/
Okay...increased risk with synthetic but REDUCED risk with bioidentical!
Remember...progesterone is a natural push-back on estrogen's growth aspects.
Balance.
There's an interesting piece of the WHI study that's never discussed.
The study found that women who started hormone replacement late in life (synthetic by the way) had issues later on.
There are two ways to read this. Essentially, women who "missed out" on the initial window (say age 47 - 53 depending on the woman), had health issues later.
Women who started early (with the nasty synthetics by the way) didn't have these issues.
Even with the missed window, the difference was small as we went through in our estradiol review.
In a fascinating study, we looked at how CBD might "re-open" this window for women who start hormones later. That full review is here.
Again, this is mainly for women who are seeing longer-term drops in progesterone and estrogen (perimenopause and menopause).
Hormone replacement wouldn't make sense for monthly cycles with temporary drops in progesterone and estrogen.
There is, however, an argument for supplementing the key pathway we discussed above:
- Tryptophan to serotonin.
- CBD for serotonin rescue (see CBD and serotonin).
We covered CBD and PMS here.
Postpartum depression is a total drop in progesterone following delivery. We looked at pregnenolone which supports all steroidal hormones but most importantly, there's a metabolite called allopregnanolone which is the basis for the new blockbuster post-Partum depression treatment.
See pregnenolone for more info or our review on postpartum depression.
Ways to protect against the growth side of estrogen
Here's the important takeaway...there are ways to protect against too much growth on the alpha receptor:
- Progesterone is a powerful counterweight to estrogen's growth excesses (must be bioidentical)
- Beta receptor boosters are also protective - Siberian rhubarb, phytoestrogens like soy (organic), and even the like
- Anti-tumor agents like NAC, fisetin, metformin, berberine, CBD, and Vitamin D are important to curb wayward cells (search up top for guides)
The whole theory of bi-est which combines estriol (e3) and estradiol (e2) is based on the beta receptor angle.
E3 hits beta receptors more and is therefore taken to be protective against the growth side.
Check out the research on Siberian rhubarb which has profound effects on peri and menopause mental health issues like anxiety, depression, anger, and mood.
Again...it's a big beta-receptor player.
Nature's way to range-bind estrogen's growth factor is in fact...progesterone.
Also, the system that kills cancer before it starts is the immune system and it just so happens that our endocannabinoid system keeps it in balance!
See CBD and cancer to learn more.
One side note...we feature turkey tail in the cancer review.
An interesting example of just how powerful estrogen is for mood.
We try all sorts of supplements personally along this journey which is why we have deep dives on berberine, Vitamin D, glycine, etc.
Our founder tried the turkey tail after dialing in the hormone piece (everyone's different...get a Dutch test).
Her mood dropped pretty significantly. She stopped and her mood came back.
Why would this happen from a simple mushroom?
It turns out that the main cancer-fighting chemical in turkey tail mushrooms called PSK has a side gig…
It's an aromatize inhibitor!
Translation...it blocks the conversion of estrogen!
Don't discount the power of estrogen for brain health (we haven't even touched on dementia), mood (see CBD and perimenopause mood changes), and mental health.
Oh...and pain, sleep, immune, heart health, and more.
Didn't want to leave that out since they're all intertwined! Check with your doctor or naturopath about Estrace (oral, bioidentical estradiol).
Be well. Take care of each other. Take care of yourself.
This glimpse into perimenopause is just the beginning. 'Dre's Story' offers our complete, research-rich journey into hormones, tools to feel better, and safety. The full Perimenopause Toolkit with new additions can be found Here. Please review so other can learn. Feeling better starts with understanding what is happening.
Related Guides:
Progesterone and Mental health Guide
My Estrogen Journey - Fighting all the Way
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.