The number one search result in Google for "perimenopause numbness and tingling" states there's no connection.
We beg to differ!
This quick ability to dismiss a slew of different symptoms during this transition is nothing new.
Granted, there are other things that can cause numbness and tingling (neuropathy from diabetes and other issues, etc) but the timing sure is suspect.
I personally ran the gamut of symptoms including:
- Restless legs
- strange shocks (like mini, brief seizures),
- strobe lighting effects in corner of my eye
- Chronic, neuropathic pain in my feet
It's been a joy.
90% of this is gone with hormone replacement, CBD, and a merry band of supplements.
The brain fog (see CBD for perimenopause brain fog) made me think I was having early-onset dementia (I now feel better than I have in a decade) but the strange zaps that would shake me out of sleep really scared me.
Let's look at what's going on here as the medical community continues with their benzo and SSRI scripts.
Of course, hormones are front and center.
We'll cover these areas:
- Can perimenopause cause numbness and tingling
- Estradiol and nerve function
- Progesterone and nerve function
- Can CBD help with numbness and tingling
- Other important tools for numbness, tingling, and neuropathy
- How much CBD to take for numbness and tingling during perimenopause
Let's get started.
Can perimenopause cause numbness and tingling
First, a lay of the perimenopause land.
It's a primary transition of two dominant hormones in our bodies and brains.
- Estradiol (our main estrogen - see full review here)
This is not just about making babies or even governing your cycle.
These hormones are deeply woven into almost every pathway of your body.
Your nervous system does not get a pass!
Here's the deal.
- Progesterone has been dropping since your late 30's (at 50% of peak by age 40)
- Estradiol can go on a wild wind-down period during perimenopause
The latter is what contributes to 25% of women who have debilitating perimenopause transitions. (Hello, my name is Andrea - my perimenopause hell is here).
Learn all about is at our perimenopause versus menopause review.
Eventually, after this flutter of activity (estradiol can peak to levels higher than pregnancy), they both decrease significantly as our period stops.
What does this have to do with numbness and tingling?
Let's drill down further into the pathways affected by each hormone.
Estradiol and nerve function
First, understand that estradiol works like a steroid in the nervous system. It has a pro-growth bent in many pathways.
That's why certain areas of the body (skin, hair, vagina, etc) atrophy or wither as we lose estradiol.
In fact, there are two receptors in the body: Alpha and Beta.
Most of the pro-growth (as in preparing for babies) happens at the ERa receptor
Many of the house-keeping effects happen at the ERb receptor (big impact on mood, sleep, etc).
Let's look at the pro-growth area first since neuropathy can be caused by atrophy in the actual plumbing of our nervous system.
Let's introduce BDNF (see CBD and BDNF).
This is the superstar behind how serotonin works and works like fertilizer for our nervous system.
Repair. Maintenance. Construction.
Why does estrogen matter here?
Estrogen-sensitive response elements are present on the genes for both BDNF and VEGF, and they are potent modulators of neuronal, glial, and vascular function, making them logical candidates to mediate the multitude of effects of estrogen.
They can actually see the new spines grow on nerves from BDNF. Check out the image here:
Here's the important piece:
The suboptimal regeneration of peripheral nerves presents a challenge in medical care. Neurotrophins, particularly BDNF, have been studied for their pro-growth properties, and treatments that stimulate endogenous release of neurotrophins have been successful in enhancing regeneration in animal models
Healthy nerve function is a result of growing and pruning connections.
There's a careful balance in this "landscaping" and estrogen is critical for the growth side.
They also found that progesterone supported estrogen's role in promoting nerve growth.
There's also the question of too much estrogen.
Restless leg syndrome was associated with estrogen levels.
Women with RLS showed higher levels of estradiol during pregnancy compared to controls (34,211 ± 6,397 pg/mL vs. 25,475 ± 7,990 pg/mL, P < 0.05).
Estrogen has also been shown to boost NMDA receptors which are key to neuropathic pain.
These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.
To translate, estrogen (estradiol) made rats more sensitive to nerve pain primarily by boosting activity at the NMDA receptor.
NMDA is where glutamate, our natural gas pedal, operates.
This also speaks to pain sensitivity differences during PMS with peak estrogen.
Keep in mind that during perimenopause, estrogen can explode to levels not seen before.
In the end, estrogen is all over nerve function.
In fact, it can even control the ability of nerves to transmit signals!
The post-menopausal women with peripheral neuropathy had significantly lower MNCV and serum estrogen and progesterone levels as compared to control subjects.
They statistically determined that the estrogen level was the main lever.
We'll leave with this before moving on:
Serotonin receptors are reduced or eliminated by the relatively rapid reduction in estrogen during the postmenopausal period, and damaged nerves exhibit hyperexcitability due to abnormal expression of Na+ channel subtypes.
Serotonin receptors. "Reduced or eliminated".
The net effect...hyperexcitability in nerves (the NMDA from above).
As for the pain side, the effects of estradiol have been known for a while but new research is pointing to exact pathways:
17β-Estradiol Attenuates Neuropathic Pain Caused by Spared Nerve Injury by Upregulating CIC-3 in the Dorsal Root Ganglion of Ovariectomized Rats.
To translate, estrogen (estradiol) was able to normalize a specific pathway in a certain part of the brain after loss of ovaries and reduce nerve-related pain.
We're going to need a full review of perimenopause nerve pain and new insights with calcitonin.
Very fascinating if you have unexplained back or foot pain (like I do). See CBD and perimenopause pain for now.
It's important though since peripheral neuropathy (retrenchment of nerves in your limbs primarily) has the following side effects:
Numbness, tightness, and tingling, especially in the legs, hands, and feet.
And the connection with estrogen?
It is the decline in serum oestrogen level which is critical in the development of peripheral neuropathy.
There's also a "skin-deep" effect on losing estrogen. Estrogen promotes skin and hair growth or replenishment.
When it drops, there is atrophy in these tissues. The net effect of this?
Skin loses its suppleness, with a feeling of intense tingling and formication owing to the effect on the neurovascular network in the skin collagen, which is largely influenced by sex hormones, especially estrogen, which declines after menopause.
So when your doctor tells you that your near-zero estrogen levels are just fine for your age, remember this:
In addition, estrogens regulate the function of the nervous system by acting on glial cells13,14, which are involved in a large variety of functions, including the regulation of neuronal metabolism, neuronal activity, plasticity, and neural regeneration.
Then go find another doctor.
Let's look at the other side of the pond for healthy nerve function.
Progesterone and nerve function
Progesterone is all over nerve function.
In general, it's protective for our entire nerve pathway where estradiol is pro-growth and excitatory.
You can think of progesterone as good cop to estrogen's bad cop (but you need both!!).
A quick summary look:
The functions of progesterone are indicated by the findings that it stimulates neurite outgrowth from dorsal root ganglia sensory neurons in explant cultures, accelerates the maturation of the regenerating axons in cryolesioned sciatic nerve, and enhances the remyelination of regenerated nerve fibers.
Okay...that's a mouthful. Let's break it down. Our nerves depend on it!
- First, progesterone spurs proper growth of new connections
- Spurs repair of generating nerves
- Repairs the padding that protects nerves
That last one...called myelination...is a game-changer.
This is the protective sheath that keeps your nerves intact and the messages flowing.
Here's the kicker for women:
The formation of myelin sheaths around axons is a sexually dimorphic process, as the sheaths are thicker in females than in males regenerating nerves.
Goodness...the very heart of our nervous system is supported by progesterone and it's dropped by 50% at age 40.
Studies looked at the effect of progesterone treatment following nerve damage:
CCI also caused a significant reduction in motor and sensory conduction velocities measured in the sural and tibial nerves, respectively. PROG at doses of 6 or 12 mg/kg induced a significant recovery of all electrophysiological changes.
CCI is the induced nerve injury. "Significant recovery".
Remember how there was too much activity at the peripheral nerves via glutamate and NDMA?
What's the opposing force there?
Let's introduce allopregnanolone...a metabolite of progesterone.
Technically, it's called a neurosteroid and is the basis for the new blockbuster postpartum depression medication (you can boost it with pregnenolone here).
Back to GABA (key to anxiety by the way), what does it do there?
Neurosteroids are considered the most potent endogenous modulators of GABA-A receptors. Its production and levels decrease in acute and chronic painful conditions.
What does it feel like?
This is how researchers put it:
The behavioral effects and physiological consequences of allopregnanolone resemble benzodiazepines and ethanol.
Benzos and alcohol but without the addiction and cancer.
No wonder so many women during perimenopause are self-medicating with wine. Also, see CBD versus benzos for anxiety here.
Back to our pathway of too much glutamate activity at NDMA receptors in nerves:
Allopregnanolone (allo) are able to protect central nervous system (CNS) neurons against the neurotoxic action of N-methyl-d-aspartate (NMDA) [3,4] and to decrease cell death and cognitive deficits after traumatic brain injury.
To add insult (age) to injury (perimenopause hormone drop):
The production rate and levels of neurosteroids decline rapidly with age, increasing the vulnerability of neurons to neurodegenerative processes.
We're getting hit twice, ladies.
Can CBD help with numbness and tingling
We've covered a great deal above.
Let's zero in on research for these pathways tied to tingling and numbness:
- CBD and serotonin balancing for nerve function
- CBD and gaba/Glutamate balance for nerve function
- CBD and neuroinflammation for tingling and numbness
The perimenopause effect all has to do with estradiol and progesterone management being sacked.
Those two pieces are critical and other "remedies" may be whistling in the wind until that ship is righted.
What about CBD in this pathway?
CBD and serotonin balancing for nerve function
We saw how depleted estradiol drops serotonin function.
Does CBD support that pathway?
We'll start in the nervous system:
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
What's allodynia? Oh just nerve sensitization to pain (exaggerated).
It's your systemic nervous system response when it's running too hot.
We'll throw in anti-anxiety and the most important word there…"normalized" 5HT.
5HT is code for serotonin.
Normalize is very important since we don't want it too high or too low (see CBD versus SSRI and serotonin syndrome).
Another study on depression found similar effects:
Our results suggest that the antidepressant-like effect induced by CBD in the FST is dependent on serotonin levels in the central nervous system (CNS).
If you read our article on exactly how SSRI's work, you'll know that the real star of the show downstream is BDNF.
What about CBD and BDNF...our nerve's fertilizer?
CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6).
Check out CBD and BDNF for much more information.
Next up...a critical system.
CBD and gaba/Glutamate balance for nerve function
Serotonin has a role here but remember how hyperexcitability can cause nerve damage and dysfunction.
First, is the endocannabinoid system (where CBD supports) even involved in the nerves?
At a cellular level, CB1 receptors are found mainly at the terminals of central and peripheral neurons, where they usually modulate the release of excitatory and inhibitory neurotransmitters.
Excitatory (glutamate) and inhibitory (GABA) neurotransmitters.
This came down to an imbalance between glutamate and GABA at NDMA receptors in peripheral nerves.
In a study of autism (ASD), powerful effects were found with this key system:
Thus, CBD modulates glutamate-GABA systems, but prefrontal-GABA systems respond differently to ASD.
Maybe one of the most fascinating results looked at schizophrenia as a result of maternal viral exposure:
Overall, these findings show that CBD can restore cannabinoid/GABAergic signaling deficits in regions of the brain implicated in schizophrenia pathophysiology following maternal poly I:C exposure.
Check out our CBD and schizophrenia comprehensive review to understand why this is so important.
As for nerve issues, the GABA/Glutamate system is critical.
There's new research that looks at ketamine to block NDMA hyperactivity in peripheral nerves for complex regional pain syndromes and nerve pain.
Look at this experiment:
CBD significantly augmented the activating effects of ketamine, as measured by the activation subscales of the BPRS. However, CBD also showed a non-significant trend to reduce ketamine-induced depersonalization, as measured by the CADSS.
So… it improved the NMDA calming effect but blocked the negative side effect from systemic ketamine use.
Ketamine is a known NMDA blocker. I personally have used topical ketamine on my heels and it definitely helps without the psychoactive effects.
What about inflammation in our nerves?
CBD and neuroinflammation for tingling and numbness
We wrote an entire review on this at our CBD and neuroinflammation since it's present across new research for almost every issue.
Neuropathy can be the end result of an immune system that either targets our nerves directly or as collateral damage.
You can think of tingling and numbness as discount nerve damage. Early signs of nerve dysfunction.
The immune system governs this:
Peripheral nerve damage activates glial cells, which release inflammatory mediators and stimulate the production of pain signaling molecules (e.g., glutamate, substance P, calcitonin gene-related peptide); prolonged release of pro-inflammatory mediators can cause central nervous system changes that may result in neuropathic pain.
There's that glutamate (excitatory). And we have a member of the calcitonin family.
The glial cells are where we want to focus since they're in charge of how to respond at the local site.
In a study of one of the more severe nerve-related diseases, MS:
we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia.
All that other stuff??? Inflammatory agents which can do more damage if left unchecked chronically.
Again, check out CBD and microglia here.
Let's look at a powerful example of this effect.
Paclitaxel is a well-studied chemotherapy agent. One of its common and most frustrating side effects:
Peripheral neuropathy (numbness and tingling of the hands and feet)
CBD's effect there?
Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy.
We're going to drop our mic on that one.
Let's quickly look at other tools.
Other important tools for numbness, tingling, and neuropathy
- Vitamin B6 (B complex really) - this is key for proper nerve function
- Siberian Rhubarb or estradiol - support of estrogen's role is still critical (Estradiol review here - Siberian Rhubarb here)
- Salmon Calcitonin - I'm about to test this now for the heel nerve pain. I'll post my results
- Pregnenolone - mother of steroidal hormones including progesterone and allopregnanolone
- Fisetin - powerful anti-inflammatory
- Berberine - improves gut inflammatory response
On to some practical questions.
How much CBD to take for numbness and tingling during perimenopause
We don't have hard research here yet.
A generally accepted test dose is around 25-30 mg to see how your body responds.
We can focus on the BDNF and serotonin function of CBD.
Studies showed that neurogenesis (building new nerves) peaks at 300 mg.
It starts to go down from there so we wouldn't want to go higher than that for nerve support.
Of course, work with your naturopath with any supplement and make sure any tingling or numbness does not have some other cause.
What about the type of CBD for nerve support?
The best CBD for nerve support
We start with the basics:
- 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).
Next up is full-spectrum CBD versus CBD isolate.
All the research at NIH and summarized across our reviews (100's of studies) are based on CBD isolate.
The full spectrum push is marketing until we see hard research.
Here's the deal...women in perimenopause are at the eye of the histamine or allergy storm.
40-60% of the population has histamine issues and this number goes up as we get older…. And for women!
Now read this little bit:
The term ‘neurogenic inflammation’ has been adopted to describe the local release of inflammatory mediators, such as substance P and calcitonin gene-related peptide, from neurons. Once released, these neuropeptides induce the release of histamine from adjacent mast cells.
There's that calcitonin again. And voila...Histamine release!
The last thing we want is full-spectrum CBD with all that plant material causing its own histamine release!
That's why so many women have bad first interactions with CBD. You'll see it all over our reviews.
Hopefully, we provided some guidance on CBD and numbness or tingling. Make sure to eliminate other sources but now you know just how powerful your estradiol and progesterone are in the nervous system.
Now if your doctor can catch up.
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.
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.