This isn't just being tired.
It's similar to your energy level during a bad flu.
Hard to actually move.
I would find that a stressful day would leave me on zero reserves both physically and emotionally during the height of perimenopause.
You can actually "feel" your breaking point with the fatigue and exhaustion that sets in.
This was despite swimming almost every day, taking supplements, and doing everything I was supposed to do.
Turns out...hormones are important!
We'll get into all of that below but maybe, more importantly, we'll look at what research is showing for CBD and other tools to fight exhaustion and fatigue.
We'll cover these topics:
- Why does perimenopause cause fatigue and exhaustion
- Hormones like estrogen for fatigue during perimenopause
- Perimenopause and sleep for fatigue
- Thyroid activity during perimenopause for fatigue
- Can CBD help with fatigue and exhaustion
- Other remedies and vitamins for perimenopause exhaustion
- How much CBD for perimenopause fatigue
- The best CBD for perimenopause fatigue and exhaustion
Grab a cup of coffee and let's get started.
Why does perimenopause cause fatigue and exhaustion
Many women are taken by surprise from this result.
They're not really warned although some may have had an introduction during pregnancy (big clue).
First, understand that perimenopause is not a slow reduction in estrogen. At least, not for most women.
Progesterone starts dropping late 30's/early 40's but estrogen can go through a spasm as we approach perimenopause.
Usually around age 47!
We look at this transition in detail at our perimenopause versus menopause review.
Essentially, estrogen can go on a roller-ride as the body tries to produce one more egg.
Wild swings with increases higher than during pregnancy followed by drops.
But estrogen is just for making babies or for our periods, right?
Estrogen is so intimately tied into our energy, sleep, and almost every facet of our health (physical and mental).
During perimenopause, it's in a period of flux. During menopause, it's gone!
We'll look at the pathways below but first, an overview of the effects on energy from perimenopause.
First, we're talking about millions of women and a host of issues (many of which we have dived in already):
The menopause transition is experienced by 1.5 million women each year and often involves troublesome symptoms, including vasomotor symptoms, vaginal dryness, decreased libido, insomnia, fatigue, and joint pain.
We've covered each of those but let's now focus on the second to last one...fatigue.
Here's the kicker...when researchers looked at a large survey of women and their perimenopausal, one lept out:
The most common symptom experienced by perimenopausal women was fatigue (54.24%), which was the only single symptom that accounted for more than 50% of all symptoms.
Goodness! It accounted for 50% of ALL symptoms.
Another large study of Chinese women found similar results:
The most frequent five symptoms were fatigue (75.84%), insomnia (69.39%), irritability (67.02%), palpitations (62.78%), and depression (61.88%). The prevalence of 14 symptoms was significantly higher in the postmenopause compared with the perimenopause status group (all p < .05).
The top two are intimately tied of course and we'll look at that below.
What about chronic fatigue syndrome? Is there a tie-in there.
Just a little.
First, 80% of the diagnosis is for women (hello, hormones).
But maybe more telling:
The prevalence of CFS is highest in the 40–49-year-old age range.
Ding ding ding!
For a final word, let's look at the effects of ovariectomy (surgical removal of ovaries for cancer protection):
The most common symptoms reported were as follows: feeling tired/lacking energy (88%), loss of libido (87%), and hot flushes (83%).
It's not just physical as we mentioned up top...what about cognitive or thinking exhaustion (you know what I'm talking about...like trying to make your way through this article :)
Again, women who had ovaries removed:
We found that cognitive fatigue is frequent in oophorectomized women and negatively associated with self-perceived health and positively associated with BMI.
So, it's a big deal tied to perimenopause.
What' exactly is driving it if we know that perimenopause is a period of intense hormone flux and drop?
Let's go there now. Turns out, we're really complicated.
Hormones like estrogen and progesterone for fatigue during perimenopause
The big players during perimenopause are estrogen and progesterone.
Unfortunately, they have their fingers in many pies across the body.
Energy production does not get a pass!
Let's start with the lead actor...estrogen.
We did a full review of estradiol (our main estrogen) here because there's so much confusion out there.
One thing is clear, estrogen is very important to the female body and brain.
What about energy?
Let's focus on three key areas:
- Estrogen and serotonin function for fatigue
- Estrogen and insulin/sugar function for fatigue
- Estrogen and metabolism
Let's start just there. Keep in mind that mood and sleep are paramount for energy levels.
We'll look at them in detail below at they are greatly affected by perimenopause.
Estrogen and serotonin function for fatigue
Most of us have heard of serotonin as our "feel good" neurotransmitter but it's much more than that.
It's a workhorse messenger in the brain and gut with hands-on many levers.
Energy levels are front and center.
Within mammalian species, the central nervous system serotonergic signaling influences both behavioral and physiological determinants of energy balance.
That's its function in the hypothalamus which is a master control for energy use and creation.
While many areas of the brain have demonstrated roles in transmitting and integrating energy balance signals, the hypothalamus is pivotal.
But it's not just in the brain for serotonin and energy balance?
Within the gastrointestinal tract, serotonin mediates diverse sensory, motor, and secretory functions.
Its effects are all over appetite by the way (see CBD and perimenopause weight) as part of this pathway.
We could go on for page and pages but what does this have to do with estrogen?
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.
That article is a wonderful look at just how all-present serotonin is across the body.
The effect of estradiol leaving the scene is found in the next sentence:
This relationship between estradiol and serotonin is prominently featured in perimenopause, when estradiol levels eventually plummet, leaving serotonin down in the dumps as well.
Basically, estradiol governs the creation and removal of serotonin, our primary housekeeping neurotransmitter.
No wonder perimenopause (and even menopause) can be a mess.
Check out CBD and serotonin here to look at how it works in detail.
Next up...the whole metabolism angle.
Estrogen and insulin/sugar function or metabolism for fatigue
Estradiol is all over the controls of metabolism...our energy and fuel balancing system.
Here's a small smattering...back to the hypothalamus..our control center:
Estrogen actions in hypothalamic nuclei differentially control food intake, energy expenditure, and white adipose tissue distribution.
A big part of this is the entire sugar and insulin complex. And it is complex!!
Why does this matter for fatigue?
Let's look at diabetes where a primary symptom is...fatigue.
Diabetes and fatigue seem to have a bidirectional relationship, both feeding and worsening each other, thereby creating a vicious cycle of DFS.
Estrogen is a key manager in all the components of metabolism and when it leaves, bad things can happen:
Estrogen deficiency promotes metabolic dysfunction predisposing to obesity, metabolic syndrome, and type 2 diabetes.
One study looked at energy availability in just the brain from loss of estrogen:
A decline of 15%–25% in metabolic function in the brain was observed after the loss of estrogen by surgical removal of ovaries or reproductive endocrine aging.
Ladies...we could stop right there.
Your brain loses up to ¼ of its energy processing with loss of estrogen.
Still, think it's just for making babies?
There are dozens of studies on estradiol's effect on metabolism such as these:
In both male and OVX female control mice, subcutaneous E2 implant improved insulin sensitivity and suppressed gluconeogenesis.
Researchers are now digging further down and found that the imbalance in sugar and insulin start to affect the very powerplants of our cells called mitochondria:
Evidence suggests, however, that calcium ion availability at the sarcoplasmic reticulum of the mitochondria, which is linked to a decrease in ATP synthesis, may lead to fatigue .
Let's go there now...and yes, estrogen even operates at this basic level.
Estrogen and mitochondria for fatigue
Your energy literally comes from little, ancient bacteria that our ancestors took hostage almost 1 and ½ billion years ago.
Estrogen is all over our energy production via mitochondria.
This will get technical but we'll decipher:
We showed that estrogen, such as estradiol and estrone, was able to improve bioenergetics and antioxidant defenses in primary neuronal cultures and in human neuroblastoma cells (SH-SY5Y) by increasing mitochondrial membrane potential (MMP), ATP levels, basal respiration, and MnSOD activity.
Basically, estrogen ramped up energy and the pathways needed to clear out its waste.
ATP is is literally a little packet of energy for our cells!
Mitochondria health is a known biomarker for aging in general.
Next up, the little chemical that makes you feel focused, alert, and engaged.
Here's the point...estrogen is pro-growth in the body and brain.
Newer studies are showing that estrogen directly increases energy production in the mitochondria:
Oestrogens seem to be able to up-regulate genes coding for some electron transport chain components present in nuclear and in mitochondrial DNA.
In fact, one major chain of it (called complex 4) slows way down when we lose estrogen.
This has huge impacts not just for fatigue but also for dementia, depression, and mood. (See CBD for perimenopause mood).
Estrogen and choline for fatigue
Choline is a fascinating chemical and you're going to want to eat your daily eggs after this.
Choline feeds the acetylcholine pathway in our brain.
Think of it as the "arousal" circuit.
You remember those days when you felt enlivened and motivated.
That's partially due to acetylcholine.
Guess the two big drugs that stimulate this pathway?
Yes, caffeine nicotine. Multi-billion dollar markets so there's clearly something there.
- Caffeine enhances acetylcholine release in the hippocampus in vivo by a selective interaction with adenosine A1 receptors.
- Need further proof?
- Nicotine binds to and activates nicotinic acetylcholine receptors, mimicking the effect of acetylcholine at these receptors
- Why bring this up?
Estrogen increases the enzyme choline-acetyl transferase and stimulates the synthesis of acetylcholine, an important neurotransmitter related to learning and memory.
In fact, women that take HRT (see CBD and HRT) have better acetylcholine levels.
Ladies, this may be the linchpin for Alzheimer's and Dementia (along with inflammation).
This is not just about fatigue and arousal.
It goes to the heart of almost all cognitive decline with perimenopause and menopause.
The entire "growth" and repair complex goes down across the body and brain.
We'll leave with this to drive home the point (we really need a full article on this):
Estradiol appears to be able alone to support the survival of transplanted cholinergic neurons.
As for the effects of nicotine?
Estradiol may have nicotinic effects as well, including increasing the density of hypothalamic α-bungarotoxin nicotinic receptors (Morley et al., 1983), and facilitating the response of neurons to the excitatory actions of acetylcholine.
It's generally understood that people who smoke (beyond the addiction piece) are trying to self-medicate for acetylcholine.
And estradiol is its primary supporter in the female brain.
Goodness. Our medical field has let us down.
Speaking of which, acetylcholine is shown to directly govern our circadian clock.
Having trouble getting to sleep or going back to sleep at 4 am?
Let's go to sleep now since it directly affects perimenopause fatigue and exhausting (duhhh).
Perimenopause and sleep for fatigue
One of the big "symptoms" of perimenopause is a disruption in sleep.
We wrote an entire article on CBD and perimenopause sleep here.
The obvious results from this:
The clinical consequences of a poor night’s sleep include daytime fatigue and sleepiness, which can be subjectively measured and form the basis for a referral for a sleep study.
New studies are pointing to a more complex scenario involving health (weight, insulin, etc) and mental health (depression) as well as life situations (occupation, etc).
Here's one interesting facet to look at with the loss of estradiol:
For example, one study suggested that wake-promoting brain structures failed to show the normal decline in metabolism from wakefulness to sleep in individuals with insomnia.
Let's bring back acetylcholine, shall we:
The cholinergic forebrain arousal system acts directly on the circadian pacemaker.
They go on to say:
Cholinergic input from the basal forebrain is both necessary and sufficient for eliciting this arousal-induced resetting of the circadian clock.
And estradiol boost choline pathways.
Goodness. Also, see the effects of progesterone for sleep at our pregnenolone review.
One other note from that research:
This was paralleled by a finding of reduced metabolism in the prefrontal cortex during wakefulness, which could very well underlie complaints of fatigue during the day.
Metabolism….let's go there now.
Thyroid activity during perimenopause for fatigue
This requires a full article as the thyroid is so important.
It's also under assault during perimenopause.
Thyroid dysfunction is common, especially among women over the age of 50.
Big shocker since peak perimenopause averages around that same time.
Why is the thyroid important for fatigue and exhaustion?
These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds.
So, what's the connection.
First estradiol and the hormones of the thyroid
The results of this study revealed that serum levels of T3 and T4 decreased in ovariectomized animals and significantly increased after estradiol treatment, while TSH increased in ovariectomized animals and decreased with estradiol treatment.
Estradiol directly drives the primary thyroid hormones, especially T3.
Progesterone caused a significant FreeT4 increase that was discovered during this randomized controlled VMS trial.
We're losing both of them so the resulting hypo (too little) thyroidism is common after perimenopause.
Finally, let's get to CBD.
Can CBD help with fatigue and exhaustion
First, understand that CBD cannot replace the hormones we're losing.
Otherwise, we're just plugging holes in a dam that's coming down!
Back to CBD.
We've covered a lot here.
Many pathways in which perimenopause (and menopause) lead to fatigue and exhaustion.
Just a quick recap:
- CBD for serotonin with perimenopause fatigue
- CBD for insulin/sugar with perimenopause fatigue
- CBD for mitochondria function with perimenopause fatigue
- CBD for choline with perimenopause exhaustion
- CBD for sleep-related perimenopause exhaustion
- CBD for wake-promoting
- CBD for thyroid function
Let's dive into it!
CBD for serotonin with perimenopause fatigue
This may be one of the biggest pathways that CBD affects.
We've covered in-depth at our CBD versus SSRI's for serotonin.
Millions of women are prescribed SSRI's at perimenopause (usually for depression/anxiety).
I was put on Lexapro and it almost killed me (that story is here and how I weaned off Lexapro is here).
What about CBD's effect? Does it just boost it like SSRI's sending the brain the other way as a response (called normalization)?
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
That's one of many studies across issues from pain, sleep, to schizophrenia.
The most important word in that sentence is "modulates".
We see a lot of that...modulate, normalize, etc.
This is critical with serotonin since it's tied to so many systems.
We don't want to boost it or drop it in one direction. Both directions have nasty side effects.
The study on CBD and serotonin for schizophrenia is the best example of CBD's role in "balancing" key neurotransmitters.
Check out how SSRI's really work (hint hint...BDNF!!!) for more info.
CBD for insulin/sugar with perimenopause fatigue
This is state of the art research...brand new.
Essentially, too much activity at the CB1 (our primary cannabinoid receptor) in the liver has a host of bad effects in the liver:
Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses.
When they block this activity, it can help across these issues.
Big pharma is on a search for either antagonist (block CB1 activity) or inverse agonist (push the other way):
There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance.
The ones they come up with keep having pretty big side effects.
CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1- and CB2-expressing cells or tissues.
Let's decipher, please.
Big pharma is looking for a substance that blocks CB1 activity.
CBD does this but in a very different way.
It blocks things that boost CB1 activity!
6 or half a dozen but with very different side effects and safety profiles.
We look forward to researching on CBD and the whole metabolic complex.
There are some other powerful tools for this pathway we'll look at below.
Next up, the power packs in our cells!
CBD for mitochondria function with perimenopause fatigue
Mitochondria failure is a known biomarker of aging.
Can CBD help there?
Calcium is literally the currency of mitochondria and our cells.
It's the balance between the inside and outside of our cell governs activity including mitochondria.
What does CBD do there:
Here, we characterize the mechanisms by which CBD regulates Ca2+ homeostasis and mediates neuroprotection in neuronal preparations. Imaging studies in hippocampal cultures using fura-2 AM suggested that CBD-mediated Ca2+ regulation is bidirectional, depending on the excitability of cells.
Let's translate because this has powerful effects on cancerous cells as well.
Homeostasis is a fancy word for balance.
The effect of CBD depends on the state of the cell and it can actually cause cell death if the cell is faulty (pre-cancerous).
Check out CBD and cancer or CBD and mitochondria here.
Back to fatigue and exhaustion.
Does CBD lead to more energy via mitochondria?
Chronic and acute CBD administration increases the activity of mitochondrial complexes (I, II, II-III, and IV), and of creatine kinase in the brain of rats.
What about choline?
CBD for choline with perimenopause exhaustion
Choline is our arousal neurotransmitter and the target for both caffeine and nicotine.
What about CBD there?
Here, we demonstrate that systemic injections of CBD (0, 5, 10 or 30 mg/kg, i.p.) at the beginning of the lights-on period, increase the extracellular levels of ACh collected from the basal forebrain and measured by microdialysis and HPLC means.
Interestingly, they found the result lasted up to 5 hours.
Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control.
That's great during the day but we don't want it at night, right?
Notice the words, "lights-on period". Daytime.
We covered this in our article, Can you take CBD in the middle of the day.
What about at night?
CBD for sleep-related perimenopause exhaustion
We covered this in-depth at our CBD and perimenopause sleep or insomnia.
CBD is a big fan of GABA, our primary sleep-promoting agent.
In fact, the leading sleep agents, benzodiazepines, primarily boost GABA (albeit with nasty side effects like addiction).
What does CBD do for GABA?
Across regions, CBD increased GABA+ in controls.
Secondly, sleep is complicated with an orchestrated series of events and cycles.
We don't want to interfere with that (THC can actually disrupt our quality of sleep).
What about CBD there?
The present findings support the proposal that CBD does not alter normal sleep architecture.
CBD for wake-promoting
We touched on this part with the acetylcholine effect above but there's more research on this effect during the daytime.
Remember the master controller under assault during perimenopause...the hypothalamus?
Supporting this observation, it was also found that this cannabinoid increased c-Fos expression in wake-related brain areas, such as hypothalamic nuclei as well as dorsal raphe nuclei (DRN).
Finally, maybe the most important piece for fatigue.
CBD for hypothyroidism
Fatigue is a known (maybe THE) symptom of hypothyroidism (too little T3 and thyroid function).
We saw how estradiol and progesterone both boost this pathway.
What about CBD here?
Let's go one level down to Anandamide, the so-called bliss molecule.
In conclusion, anandamide has the ability to acutely inhibit TSH release in eu- and hypothyroid rats, acting at the hypothalamus-pituitary axis.
Interestingly, it did not have this effect when we have too little TSH (hyperthyroidism).
Elevated TSH is a sign of hypothyroidism.
Its primary symptom….fatigue.
We need more research here but it's well established that the endocannabinoid system is intimately involved.
That's anandamide...what's the connection with CBD?
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.
Let's look at other tools we found along the way.
Other remedies and vitamins for perimenopause exhaustion
- Berberine - powerful effects on insulin/sugar systems. Review here. Buy here.
- Fisetin - similarly powerful effect on inflammation. Review here. Buy here.
- Selenium - thyroid function. Buy here.
- Iodine - thyroid function. Buy here
- CPD Coline - support acetylcholine function. Buy here.
- Siberian Rhubarb - analog for estrogen with a strong safety record. Buy here
- Pregnenolone - supports dropping steroidal hormones including progesterone. Buy here
- NAD-supports natural levels that decline with age.
- B-complex- Buy here
On to some practical questions.
How much CBD for perimenopause fatigue
We don't have hard research on this front.
The generally accepted introductory dose is around 25-30 mg.
- Sleep research is pointing at about 160 mg
- Neurogenesis (hippocampus repair) peaks at 300 mg
A support level is probably between 50 - 100 mg daily depending on your system.
Start low and work up based on how you feel.
It can take a good 30 days for CBD's effects to really show since we're talking about systemic pathways (hormones are powerful!)
Again, CBD can only help support these pathways above but they are driven by steroidal hormones.
Have been for decades (until they weren't)!!
Let's look at the type of CBD...this important.
The best CBD for perimenopause fatigue and exhaustion
Of course, the basics apply for ANY CBD use:
- Organically grown in the US at an FDA certified farm
- 3rd party tested (we test both biomass and finished product separately)
- THC free (THC can actually cause psychosis)
- No pesticides
- No mold
- No heavy metals
- No bacteria
That's a baseline (which many brands don't meet).
We actually test twice (biomass and finished product) since our whole family uses our CBD.
There's another important aspect.
CBD isolate versus full-spectrum CBD for perimenopause fatigue.
Most of the market is pushing full spectrum but we're not sure based on what.
All the research (above and through our site) is based on CBD isolate. By itself.
Check out CBD isolate versus full spectrum for anxiety here to see what we mean.
This is especially important for perimenopause.
Allergy and histamine issues peak with perimenopause.
Check out CBD and perimenopause allergies to see why (hint hint...hormones).
The last thing we need is a bunch of plant material to set that system off.
CBD Isolate is the cleanest way to get the benefits listed above.
If you look at our reviews, many women try other CBD products and have bad reactions only to find that CBD isolate feels much better.
That's how we stumbled on isolate ourselves (that story is here) after 3-4 of the biggest full spectrum brands gave us side effects.
Be well. Be informed. Take care of each other. Eat your eggs...choline is queen right now!
See CBD and perimenopause brain fog to understand why!
Get specific links for CBD and Perimenopause symptoms and questions here.
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.