Finally, Some Clarity on Topical versus Oral Estrogen (bioidentical)

new research on oral estrogen regarding safety - bioidentical

We've written extensively on the sordid history of estrogen guidance and research stemming from the 2001 WHI report.


We further went into the various benefits of estrogen in the female body with a focus on mental health.


That's all well and good (though vaguely understood by the medical community).


The final question we personally had from a safety point of view with estrogen was topical versus oral.


This was the last bit of back and forth with our naturopath who we love by the way!


Our founder tried the creams and gels but invariably, they would end up irritating the skin.


With every movement of location or shift of type (gel to cream), estrogen would drop, and boy did I feel it!


Mood would drop, pain sensitivity would go up….all of which makes sense when you read our estrogen and mental health review.


Serotonin's a powerful drug!


We wanted to test oral since it would avoid this skin issue and have a more level effect (we'll touch on this below) but we got lots of pushback.


The two discussion killers are quickly thrown out: 

  • Thrombosis (blood clots)
  • Cancer


How exactly do you come back against that?


With research!


Dre's Story - Perimenopause Survival Guide 


Finally, we have hard research to dispel this 20-year myth.


We'll go through the pieces to the puzzle here: 

  • The WHI report on estrogen 
  • The dearth of data on bioidentical (why that's so important)
  • The Bijuva study 
  • Ways to Protect against excess estrogen


Let's get started.


There are 1 million new souls hitting perimenopause each year in the US and a quarter of them are going to get decimated (see why some women are hit so hard by perimenopause see our story).

The WHI report on estrogen  

We'll leave why estrogen is important to every pathway in your body to our estrogen review.


Many women realize this during perimenopause when it can go through a roller coaster ride and then plummet (similar to 3-4 days before the period) into menopause.  


We've covered perimenopause in-depth here!


Let's focus on the safety aspect of supplementing.


Hormone replacement was actually the most prescribed medication in the US for quite a stretch up until 2001.


This all changed with the WHI massive study which led to the headlines…


HRT increases the risk of blood clots, strokes, and cancer.




Millions of women promptly came off of their HRT at their doctor's advice.


We dug deep into that flawed study at our Estradiol review as we're equally concerned.


One of our doctors literally grabbed me by the arm when I asked for bioidentical progesterone (see progesterone review) and warned me..


"You'll have a stroke!!"


That's great to hear when you experience rolling panic attacks and anxiety from a loss of progesterone and estrogen.


What did the report actually find?


It found an increased risk for women who started HRT later in life but the main point…


It was all based on synthetic hormones!


Let's go there because this is the crux of the argument.

The dearth of data on bioidentical (why that's so important) 

The WHI study and 99% of studies all focus on synthetic hormones.


Primarily CEE or estrogen derived from horses. Premarin was the big brand.


Most doctors today still don't distinguish between synthetic and bioidentical in terms of safety and effectiveness.


In fact, we asked our doctor friend and she said, "bioidentical hormones are a rip-off".


Unfortunately, the medical community has outsourced their knowledge base to pharma reps who are more than happy to sling synthetics that cost pennies to make.


Almost all birth control is synthetic progesterone.


Saying that synthetic hormones are the same as bioidentical couldn't be further from the truth.


First progesterone…


Breast cancer: 

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.


Goodness...a 33% reduction.




A meta-analysis of 3 studies involving 86 881 postmenopausal women reported that the use of natural progesterone was associated with a significantly lower risk of breast cancer compared with synthetic progestins


Goodness...bioidentical reduced risk while synthetics increased them.



The studies reviewed suggest bioidentical progesterone does not have a negative effect on blood lipids or vasculature as do many synthetic progestins


Okay...progesterone was less of the question but what about estradiol (our primary estrogen)?


Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures.


Potentially opposite.


Perimenopause book for women


How can that be if every doctor and their pharma rep is saying they're the same?


You would think we would have learned our lesson by now.


Slightly similar molecules do not interact exactly the same.


We have a laundry list of examples: 

  • Hydrogenated oil - one hydrogen added to oil - almost wiped out a generation with heart issues
  • Chlorinated sugar - one chlorine added to sugar (fake sugar) - see gut inflammation to learn more


Even the synthetic version of CBD (called epidiolex) has nasty side effect profiles that don't show up with CBD isolate.


Night and day.


There are multiple versions of THC that all pretty much the same chemical structures and different effects.


See Delta 8 versus CBD as an example.


This is where we get angry.


There's a total lack of due diligence when it comes to women's health and hormones OUTSIDE of reproduction.


In fact, most doctors just think estrogen and progesterone are primarily for reproduction.




They are intimately tied into every pathway of your body and brain.



They both work to manage your actual heartbeat rhythm!!  Literally, shape it!


So...we told millions of women to drop their progesterone/estrogen because "your numbers are fine for your age".


The problem is that every study was on synthetic so the constant pushback from our doctor pointed to this risk.


We went through study after study including the big French one but synthetic muddied all waters!


The French study showed that topical (usually applied to the labia) estrogens (still synthetic) were better than oral (synthetic).


Same problem with the synthetic nonsense in the mix.


Perimenopause book for women


Until now.


Thank you Bijuva.

The Bijuva study  

We've been waiting for this to make its way through the FDA gauntlet.


Originally called TX-001HR, this drug combines bioidentical estradiol and progesterone for ORAL delivery!


We finally have the results and this should be the biggest news for women's health!


We looked at the issues referenced in the big French study: 

  • Thrombosis (blood clots)
  • Cancer (excessive growth called hyperplasia) 


The results were just as we expected.


First...the cancer risk: 

Reported at a rate of ≤1% in women receiving BIJUVA consistent with the expected incidence rate in a postmenopausal population1,3


So, no difference between women in menopause in general.


As for the blood clot worry with oral estrogen: 



Remember that the big French study (biggest bugaboo regarding oral estrogens) showed risk in the first year but not after.


The Bijuva study then looks at various metrics tied to the blood clot issue and they are all the same or better than women not taking it.


  • Fibrinogen dropped from 9.4 to 9.1 - fibrinogen is tied to the clot-forming process
  • Thromboplastin has a lower increase than placebo which means it actually was beneficial
  • Prothrombin decreased with Bijuva where it increased with placebo


If anything, it appears that bioidentical progesterone and estradiol are beneficial for managing the clotting process.


The fascinating piece while looking at the results from the very thorough FDA safety testing requirements is this!


They still had to print the results of the WHI studies even though they were completely countered by the actual study results!


If you read our million+ words of research, we're not big fans of pharma (see CBD versus SSRIs or CBD versus benzos).


Here, we have to give credit to Bijuva for actually focussing on the real health metrics of bioidentical and putting it through its paces with an oral delivery.


This one study decimated 2 decades of unneeded pain and suffering for women:

  • Bioidentical progesterone and estrogen
  • Oral delivery
  • Estradiol by itself


The final piece is interesting as there's a big push of bi-est which is estradiol combined with estriol (E3).


We covered the different estrogens in detail but the main push was to use E3 to protect from the pro-growth push of estrogen (the cancer piece).


Let's look at this as an insurance policy if you will.

Ways to protect against excess estrogen 

This really gets down to which estrogen receptor our 3 versions of estrogen plug into and at what strength.


As for the receptors:

  • E alpha is our pro-growth side 
  • E beta is our maintenance side and it can protect against E alpha's pro-growth if excessive.


There are ways to do this separately and still get the powerful benefits of estradiol.


An insurance policy if the Bijuva study is unable to completely eradicate 2 decades of fear.


The whole push for bi-est (with estriol added to estradiol) is that estradiol hits E beta more than E alpha.


This is thought to be protective from too much growth from estradiol.


Interestingly, estriol (E3) only kicks up during pregnancy and explodes in levels.


It's like a backup estrogen to juice the system during this highly pro-growth time.


There are other ways to stimulate E beta receptors for protection as well.


The big ones are: 

  • Siberian rhubarb - see full review here
  • Phytoestrogens - like from organic soy products


Just a head's up...90% of soy in the US uses nasty pesticides like glyphosate which is going in the wrong direction.


These substances act like SERMS such as tamoxifen used for breast cancer.


They are powerful E beta boosters for protection.


There are other powerful tools that support our immune system to deal with cancerous cells.


Anti-tumor agents like NAC, fisetin, metformin, berberine, CBD, and Vitamin D are important to curb wayward cells


Our main focus was the oral versus topical estrogen piece since topical became a dead-end for us (skin irritation...especially on the labia) and it wore off as the day went on.


The Bijuva is the first (that we can find) study looking at bioidentical progesterone and estradiol (our primary estrogen) taking oral which address these concerns.


Give it another few decades for our medical community to 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. 

Dre's Story - Perimenopause: A Surivival Guide

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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