Is it too late for HRT? Can CBD Re-Open the Window for HRT Benefits If Started Later?
The scaremongering that likely started an epidemic in dementia, heart issues, and many different issues back in 2002 did carry one morsel of useful information.
We're referring to the WHO study which caused doctors and millions of women to suddenly drop hormone replacement therapy.
It's amazing how many doctors still cling to this flawed report.
My second doctor literally grabbed my arm and warned me that I would get a stroke from bioidentical progesterone.
Despite the fact that at 47 and in full-blown perimenopause, I was completely spiraling.
One of the lucky 25% that experiences a debilitating transition.
So back to the study.
What did come out was this…
Women who waited until later to START HRT missed out on the benefits of doing so.
Keep in mind that they were dealing with synthetics or horse-derived hormones back then which have their own issues.
Even with that, the risk was starting too late!
Of course, this data was "blended" across the entire body of work and led to scary headlines of cancer and blood clotting.
Again, please read the full estradiol review to understand the real situation.
Then tell your doctor, please.
After reviewing research on CBD effects across a range of perimenopause issues (heart, mood, nervous system, pain, etc), estradiol and progesterone's roles in women's bodies are so important!
Estradiol alone is a master regulator with its foot on the gas pedal for serotonin.
You know… just our "feel-good" neurotransmitter and master-controller in its own right.
Let's look at this gap if we try to start HRT when we're older.
- HRT after 50
- HRT after 55
- HRT after 60?
Is there a way to still get the benefits of estradiol and progesterone if we start older?
Fascinating new research on CBD may hint at a reset button.
Let's check it out.
We'll cover these areas:
- The benefits of HRT
- Is it too late for HRT
- Can CBD re-open the window for HRT if older
- Can you take CBD with HRT
- How much CBD to take with HRT when older
- What's the best CBD to take with HRT in menopause
Let's get started.
The benefits of HRT
The easier way to address this question is to look at what happens when estradiol and progesterone are ripped away at perimenopause.
Here are links with in-depth looks at their pathways for specific perimenopause symptoms and systems:
- Can CBD help with perimenopause mood
- What are CBD's benefits for perimenopause sleep
- Can CBD help with perimenopause aches and pains
- Can CBD help with perimenopause weight gain and issues
- Can CBD help with perimenopause allergies or histamine response issues
- Can CBD help with perimenopause brain fog or cognitive issues
- Can CBD help with perimenopause fatigue and exhaustion
- Can CBD help with perimenopause blood pressure or heart palpitation issues
- Can CBD help with perimenopause neuropathy, tingling, and numbness
- Can CBD help with perimenopause anger and irritability
- Can CBD help with perimenopause migraines
- Can CBD help with perimenopause nausea
- Can CBD help with perimenopause anxiety
- Can CBD help with perimenopause depression
So… just those things.
Actually, estradiol (our main estrogen) and progesterone are pretty well integrated into almost every pathway in our body.
We didn't even cover bone health, maybe one of the most pronounced pathways for HRT.
It's actually quite fascinating how mother nature will dual-purpose a given chemical in the body/brain.
Men do not have nearly the levels of estradiol so many of the housekeeping functions held by estradiol are handled differently in men.
The fact that estradiol and progesterone literally shape our heartbeat is a good example.
Here's the key takeaway:
- Estradiol is a powerful pro-growth and housekeeping master-regulator
- Progesterone is a powerful agent for calming inflammation and offset to estradiol's pro-growth ways
Without estradiol "replenishing" effects, entire systems will begin to atrophy or wither away.
It's obvious in the skin and hair.
What about the brain (dementia), heart (cardiovascular disease), bones (osteoporosis), nervous system (mood, depression, etc).
Before we move on, let's pull back the curtain to understand why these two yin-yang hormones operate this way.
Think of your monthly cycle from before.
- Their effects are all tied to reproduction.
- Estrogen would literally build for potentially supporting a new fetus.
- Progesterone would then release after the egg to potentially protect the amniotic sac from being attacked by the immune system.
The amniotic sac is actually made from the father's DNA so it looks like a foreign entity to the immune system.
Progesterone calms this response system-wide (hello autoimmune diseases and histamine issues when progesterone drops).
We digress but it's interesting to understand why these two players operate the way they do.
Mother nature just dual purposed them for other tasks out of efficiency (growth support for estradiol and antiinflammatory/calming for progesterone).
You see the signature of these effects all over the body.
So…. THAT's why they're important to a woman be it at age 18, 47, or 60.
Is there ever an age to lose vitality?
The problem is that the 2002 study really scared everyone.
Major sites online still regurgitate the bogus take-away from that study TODAY!
Again, read the estradiol review to really understand the safety of HRT.
For this reason, many women either stopped or never started HRT beyond perimenopause.
Can't you just start up HRT later in life to get the benefits?
Is it too late for HRT
When they finally went back analyzed that WHO data, they found this.
Women who started HRT late had higher risks than those who started early.
Essentially, there was a level of damage that occurred by not having those hormones functioning for a period of time.
This makes sense since they're so critical.
Researchers now fully have a hand on this effect parsed out from the original study:
There is a substantial increase in quality-adjusted life-years over a 5–30 year period in women who initiate HT in close proximity to menopause supporting HT as a highly cost-effective strategy for improving quality-adjusted life.
More detail points to a 10-year window from initiation of menopause.
The total from the data indicates that the “window-of-opportunity” for reducing CHD and overall mortality is the initiation of HT before 60 years of age and/or within 10 years of menopause.
Let's backtrack a bit.... when does menopause really start?
If you read our perimenopause versus menopause article, you'll see that it's officially kicked off after 12 months with no period (with no following period to occur).
This generally occurs from age 47-50 but can be much earlier for some women.
Keep in mind that progesterone has been dropping for some time now and is at 50% of year age values by age 40!
Estradiol then plummets during perimenopause and both drop significantly during the 12-month transition from perimenopause to menopause.
So… according to all the data, the ideal time to start HRT for its benefits is during perimenopause really.
Definitely by the start of menopause.
During the 10 years following the initiation of menopause (which takes us to age 60), there is an accumulation of damage from the disappearance of estrogen and progesterone.
If you're angry about this apparent betrayal from mother nature after age 50, understand that the rules were written 10's or 100's of thousands of years ago.
Just over 100 years ago (1900), the life expectancy for women was 49.
Menopause didn't really matter till the last century!
What about starting hormone replacement later in life?
Here, it gets more nuanced.
There are really two sets of "symptoms" tied to estradiol.
- Atrophy-related symptoms such as vaginal dryness, incontinence, bone loss, etc
- Housekeeping related symptoms such as mood, sleep, cardiovascular health
In our estradiol guide, we really dig down deep to show that the first is more tied with the ERa receptor and the latter is tied to the ERb receptor.
It's not as great for incontinence, vaginal drying, and other pathways that require estradiol's powerful "replenishing" effect.
Why do we bring this up with later life HRT?
Initial studies showed that starting HRT later in life had positive effects on the so-call "vasomotor" symptoms (hot flashes, heart palpitations, etc).
That's the ERb receptor that Siberian Rhubarb is so good at.
Keep in mind that we're totally losing the powerful effects of progesterone with just estrogen pathway stimulation.
What about the pro-growth side of estradiol (ERa receptor)?
A study threw a monkey wrench in the whole equation.
Enter studies on dementia.
It found that women who started HRT early had a huge protection from dementia.
1524 women (27%) were diagnosed with dementia during the follow-up period. Compared to women never on HT, those taking HT only at mid-life had a 26% decreased risk.
But when they looked at women who started HRT later in life, there was actually an increase!
While those taking HT only in late-life had a 48% increased risk.
Now...a really big caveat…
They were using horse derived estrogen and synthetic progestins.
The fact these are still prescribed is tantamount to negligence at best.
There are lots of studies comparing the effects of bioidentical hormones and synthetics.
Just one (of many) examples with progesterone versus synthetic for breast cancer (ONE of the big boogey boos out there with doctors).
Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55–0.81.
That's a 33% reduction in risk!
And yet...millions of women are on synthetic progestins for HRT and birth control.
You can look across the spectrum of "risks" and see this effect.
This really requires a deep dive (we covered some of it in our estradiol guide) but here's the take-away…
We can't really look at the risk associated with late HRT that's based on synthetics since our bodies don't process them the same way (as evident from the breast cancer risk).
You would think we might have learned something from the following:
- Hydrogenated oils - "synthetic" oil which doomed a generation to heart risk
- Fake sugars - "synthetic" sugars which are now showing a host of issues
So… back to dementia.
There are powerful data supporting the effects of hormones in the prevention of dementia.
Researchers are final drilling down into the exact mechanisms (besides the growth support we showed in estradiol review).
Interesting new pieces of research are teasing out the mechanisms such as HRT's effect on gene risks (APOE) and cellular aging (telomere shrinking):
Women who carried APOE-e4 showed less reduction in telomere length if they stayed on HRT.
As for the dementia piece, we await research on bioidentical estradiol and progesterone started later in life.
Don't hold your breath as there's no way to profit off of such a discovery from big pharma.
Otherwise, we wouldn't still be prescribing synthetics to half our population despite the data.
If you read our CBD for perimenopause brain fog, it doesn't make sense that estradiol/progesterone (bioidentical) would do anything but protect.
Just two quick but powerful examples.
Estradiol is a powerful supporter of serotonin (controls both the creation and removal of it) in the brain.
Serotonin directly drives BDNF which is our brain fertilizer.
This is literally estradiol's pro-growth strategy for brain mass!
New research is pointing to choline as being THE key to dementia.
You can supplement it here, and by the way, my mind feels immediately clear when I take mine for perimenopause.
We're about to point you to information that shows a direct correlation between estrogen loss and dementia via choline.
This is out there in the research NOW while your doctor tells you that your estrogen levels are perfectly fine for post-menopause.
The only source of choline other than the diet is from the de novo biosynthesis of phosphatidylcholine, which is catalyzed by phosphatidylethanolamine-N-methyltransferase (PEMT) (1). The PEMT gene has several estrogen response elements in its promoter region, and the gene is induced by estrogen.
Let's translate because it's too important to miss.
- There is one way to get choline and it requires the PEMT gene.
- PEMT gene requires estrogen interaction and is actually "triggered" by estrogen.
Excuse our language but holy crap!
Their net takeaway…
Because of their lower estrogen concentrations, postmenopausal women have a higher dietary requirement for choline than do premenopausal women.
New 2019 research:
In a new study, Biodesign researchers reveal that a lifelong dietary regimen of choline holds the potential to prevent Alzheimer's disease (AD).
Eat your eggs or supplement with CDP Choline here.
To add insult to injury, the two most common classes of medication we come across for women with perimenopause or menopause are benzos and SSRI's.
Both have been shown to actually rip choline!
It's a 1-2 punch of dementia risk for millions of women. The data is all there on NIH!
There's no excuse.
That's just 2 very powerful examples of estradiol's role in protecting the brain (out of dozens if not 100's).
So… what if we want to start HRT later in life.
Is there a trick to neutralize the years of hormonal neglect?
Can CBD re-open the window for HRT if older
This is brand new and really fascinating research.
Interestingly, mice show the same "window of opportunity" for HRT.
If HRT is administered to mice who undergo ovariectomies (removal of ovaries and hence, estradiol and progesterone), they will avoid the later occurring memory and cognitive decline.
Here, we found that facilitation of memory extinction and long-term depression by 17β-estradiol (E2) was normal in mice 1 week after ovariectomy (OVXST), but it was impaired in mice 3 months after ovariectomy (OVXLT).
Keep in mind that 1 week or 3 weeks is a lot longer in mouse years.
So… if estradiol is given right after loss of hormones, there is protection.
Wait longer, protection goes away.
Here's where it gets interesting.
They found that the loss of hormones basically down-regulated activity at the CB1 receptors.
CB1 is our nervous system's primary receptor for endocannabinoid like anandamide and 2-AG.
Anandamide is the primary "key" to this receptor's lock although THC can mimic it pretty well (albeit with some downside - see CBD versus THC).
Why would the loss of estrogen affect CB1 activity?
Goodness...we told you estradiol is a master regulator.
It directly governs activity at this juncture.
In fact, researchers are looking at this interaction to explain key differences in stress and emotional response.
Such as this one…
Our data reveal that males and OVX females have higher amounts of hypothalamic and lower amounts of amygdalar cannabinoid receptor binding relative to both cycling females and OVX + E females.
To decipher that… males and females who lost their hormones (ovariectomy or OVX) had a totally different activity for endocannabinoid processing than women with HRT.
Sorry… we digress.
Here's the key point...anandamide, the main key to CB1 activity is called the "bliss molecule" named after Anand, the Hindu goddess of bliss.
Yes… you can guess what it feels like.
It also goes to the heart of stress response and a slew of other effects (less pain, less anxiety, less depression, etc).
Back to our mice.
What happens when the researchers stimulated the CB1 activity for the mice who were given HRT later?
Replenishing of miR-221-5p or treatment with a CB1 agonist rescued the impairment of fear extinction in E2-treated OVXLT mice.
The benefits of HRT came back even if started late.
miR-221-5p is a pathway affected and it turns out that women in perimenopause see a similar drop...LATER in menopause.
Blood samples from postmenopausal women aged 56–65 indicated decreases of miR-221-5p and 2-arachidonoylglycerol compared with samples from perimenopausal women aged 46–55.
That other one is 2-AG, our other primary endocannabinoid (with anandamide).
miR-221-5p is a relatively new player in our knowledge. It's tied with Nitrous Oxide pathways inlining of our cardiovascular system.
Nitrous oxide is very important in supporting the "tone" of our vasculature:
eNOS has a protective function in the cardiovascular system, which is attributed to NO production.
Interestingly...eNOS has anti-proliferating effects (anti-cancer) and anti-clotting effects.
Those are two key concerns with synthetic HRT!!
As for bioidentical estrogen's effect:
E2 significantly increased NO2 levels irrespective of its concentration in both cell lines by 35 % and 42 % (p < 0.05).
See why we're angry with the medical community on women's health and HRT!!
So...what can we do to support CB1 activity.
THC directly plugs in but it has negatives and the body will actually normalize or offset its effect by reducing our natural CB1 activity.
What about CBD?
CBD works in a very different way.
Let's first look at CBD's effect on anandamide which is designed to work with CB1 receptors.
CBD blocks FAAH which our body uses to disable anandamide.
The results of this:
Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement.
That was actually a study on schizophrenia (see CBD and schizophrenia).
What about the miR-221-5p which boosts levels of nitrous oxide in our blood vessels and arteries?
Nitrous oxide is tied to the relaxation of our cardiovascular system.
It's one reason why blood pressure goes up as we get older.
What about CBD and this pathway as a hint to up-river effects on the miR-221-5p?
Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1 activation.
It's all right there:
- Endothelium - the lining of our vascular system - the "e" in eNOS above (dropped later in menopause)
- Vasorelaxation - the direct mark of eNOS
- CB1 activation!
It's the trifecta from above with the study on mice and re-opening the window of HRT for older women.
We need more research.
The endocannabinoid system and estradiol are all-star players across almost every system in the body.
We would expect this eNOS effect is just one knock-on effect of loss of estradiol.
Having a study that shows the direct ability to re-open HRT's "window of opportunity" is hopeful and fascinating.
It definitely re-opens the question of starting HRT later in menopause.
This brings up a practical question.
Can you take CBD with HRT
We did a deep dive into whether you can take CBD with hormone replacement therapy.
Out of self-interest!
- I take bio-identical estradiol/estrone and progesterone.
- I also swear by CBD for its effects (along with a host of vitamins).
I didn't want my CBD to interfere with my hormones and vice versa.
You can check out the full review of CBD and HRT here.
In general, they are supportive of each other which makes sense when you see that the two systems (steroidal hormones and endocannabinoid system) are highly intertwined and supportive.
The one thing we did find was that CBD may slow or impede the metabolism of oral progesterone.
They both use the same pathway in the liver to process and much of progesterone's punch actually comes from the metabolite allopregnanolone (the basis for the new post-partum depression medication).
CBD metabolism may slow or impede this metabolism.
For that reason, I take it at least 4 hours apart.
That brings up the next practical question.
How much CBD to take with HRT when older
The test dose is usually around 25-30 mg to see how your body responds.
I take 150 mg of CBD in the morning and 150 mg after dinner (4 hours before I take progesterone at bedtime).
Progesterone is huge for sleep (see CBD and perimenopause sleep issues).
We don't want to interfere with that!
Why 300 mg?
Research is pointing to 300 mg as the max level for neurogenesis...a fancy way to say brain repair and replenishment.
- Estradiol directly promotes serotonin
- Serotonin directly promotes BDNF
- BDNF is our brain and nerve fertilizer (key to neuropathy as well)
Max neurogenesis was found at 300 mg of CBD.
Of course, most doctors will prescribe SSRIs to women in peri and menopause but the brain will normalize against this artificial boosting by downregulating your natural system.
Of course, work with a doctor or naturopath with any supplement including CBD.
Many women are immediately thrown on benzos or SSRIs which can be really tricky to navigate.
One final (but important) practical question.
What's the best CBD to take with HRT in menopause
Many women hear about CBD, decide to try it...and learn the hard way.
Just like we did in the beginning.
Everyone's pushing full-spectrum CBD.
The problem for women in perimenopause or menopause is that our histamine system can be on overdrive.
That's allergies for a layperson.
We go into detail why this is the case at our CBD and perimenopause allergies and histamine here.
Of course, it's the hormones! Especially progesterone.
Back to the market...we had bad reactions to 3-4 of the biggest CBD brands on the market until we found CBD isolate.
That's why we focus on Isolate in MCT oil. Just 2 ingredients.
All those reactions went away with a high-quality Isolate.
As for high quality, these requirements are mandatory:
- Organically grown at an FDA registered US farm
- 3rd party tested
- CO2 processed
- No THC (See why CBD offsets THC's negative effects)
- No Solvents
- No Pesticides
- No Heavy Metals
- No Mold
- No Bacteria
Our 3rd party testing is available on every product page and at the top of EVERY page.
We test twice for our oils since our whole family uses this product.
Starting HRT later in menopause had some serious questions but we have a way to bypass or reverse the "damage" of waiting with activating the endocannabinoid system.
We await more research to this effect.
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.