The Estrogen Wars Continue

Jul 30, 2024

Just as we are recognizing that the Women’s Health Initiative (WHI) “Estrogen Only” group of ladies, in every re-analysis, clearly demonstrated that estrogen protects breasts, we now have some experts with wide platforms vilifying estrogen.

Saying estrogen dings brain health.

Yesterday Mercola did another estrogen disservice.

But there are also some OBGYNs online almost begging women to avoid the second estrogen, estriol.

It’s as though hormones can never get a break.

Hormones might be more polemic than nutrition.

Everybody’s got an opinion.

But are women missing out all the while on the most powerful and protective anti-aging tools we have: balanced individualized hormone replacement?

And Mercola is on, I am assured by those close to him, testosterone replacement.

So his brain is protected.

All the while he keeps shouting from the roof tops that estrogen is an exotoxin.

I say “Hogwash”!

Let’s take a dive ourselves into all these fear messages yet again about estrogen.

First off, clinical acumen must trump these ups and downs of studies.

Studies have lots and lots of issues.

We are seeing that what are called “confounding factors” can mess up out comes.

Confounding variables are very hard to figure out. That is why they are called confounding.

In a cause-and-effect study, a confounding variable is an unmeasured variable that influences both the supposed cause and effect.

This is especially an issue in research like Mercola cite, that is not a cause and effect study but just looking back at statistics. Called retrospective study.

Confounding variables can mess up what you might think an outcome “really” is.

The WHI was shown by Hodis to have a terribly flawed “methodology” that misled us into thinking estrogen was not breast protective.

Hodis did a deep dive and was able to show that estrogen is so breast protective, that by not taking out the women in the placebo arm that had had estrogen therapy in their past histories, they didn’t get a true statistical outcome from the study.

This uncontrolled confounding variable actually “protected” the placebo arm.

Making it look like more breast cancer cases occurred in the experimental or estrogen arm.

This made it inaccurately look like there were more cases of breast cancer in women taking hormones, than not.

But this “uptick” of breast cancer in the experimental group was due to not controlling for that “confounding” variable.

But recurrent reanalyses over and over (almost 15 consistent reanalyses) showed that women on estrogen therapies for an average of 5 years, have greatly reduced risk of getting breast cancer in the first place.

Or dying from it if you do get it, in the second place.

This is the abstract from that shocker when Hodis showed that the WHI was fatally flawed. Due to estrogen being so very breast protective. That there was “confounding” going on.

Can’t get great statistics as important variables had NOT been accounted for.

Accounting for confounding variables is NOT EASY.

The WHI with it’s wrong bad news was first published in July 2002. And Hodis did not figure this out or publish it till 2018, 16 years later it took to figure out the issue with the not identified confounding variable!

Hodis Abstract: Menopausal hormone therapy and breast cancer: what is the evidence from randomized trials

The relationship between menopausal hormone therapy (HT) and breast cancer is complex and further complicated by misinformation, perception, and overgeneralization of data.
These issues are addressed in this mini-review through the lens of the Women's Health Initiative (WHI) that has colored the view of HT and breast cancer.
In the WHI, unopposed conjugated equine estrogen (CEE) reduced breast cancer risk and mortality.
In the WHI CEE plus continuously combined medroxyprogesterone acetate (MPA) trial, although the hazard ratio (HR) was elevated it was statistically non-significant for an association between CEE + MPA and breast cancer. (synthetic progestins are not good for the breast)
In fact, the increased HR was not due to an increased breast cancer incidence rate in women randomized to CEE + MPA therapy but rather due to a decreased and unexpectedly low breast cancer rate in the subgroup of women with prior HT use randomized to placebo.
For women who were HT naïve when randomized to the WHI, the breast cancer incidence rate was not affected by CEE + MPA therapy relative to placebo for up to 11 years of follow-up.
The current state of science indicates that HT may or may not cause breast cancer but the totality of data neither establish nor refute this possibility.
Further, any association that may exist between HT and breast cancer appears to be rare and no greater than other medications commonly used in clinical medicine.

But what about brain health?

Mercola is calling out that estrogen is bad for brains.

Mercola called out the estrogen alarm yet again yesterday.

Clinical Acumen

First off, in clinical practice, we see that most women and men on hormone therapies, have less anxiety, better cognition, and feel more like their old younger better versions of themselves.

Not a diminution of thinking.

The weight of what is seen in the clinical trenches is not small.

It is truly more how medicine evolves, or should evolve, than attempts at randomized trials.

You see how confounding can get confounding. And can take years to figure that out.

Mercola wrote:

This new analysis of women who were diagnosed with breast cancer and thus put on estrogen blocking drugs, were tracked for their risk of losing cognition.
In this retrospective cohort study, hormone therapy was associated with protection against ADRD in women aged 65 years or older with newly diagnosed breast cancer; the decrease in risk was relatively greater for Black women and women under age 75 years, while the protective effect of HMT diminished with age and varied by race in women.

Suggesting, say these actual authors, in their abstract “with no hard science”, that estrogen therapy might be bad for cognition, not good.

But these women had just been diagnosed with breast cancer.

Since I specialize in adjunctive cancer care, I know that once you get a cancer diagnosis, most people “clean up their act”.

They eat better, cut out sugar, get into thinking what can I do to protect myself - so you cannot control for this confounding variable in this not hard science that even the authors say this is not hard science, in their published abstract.

You cannot scream to the skies that this is hard science or definitively shows estrogen is brain bad.

This is very similar to the issue of confounding variables not being identified and screwing up statistical outcomes in the WHI from July 2002 that nobody figured out till Hodis took the trouble to statistically figure it all out. In 2018. It took that long.

Confounding variables are that confounding!

This is not the hard science Mercola is implying and making women yet again scare of estrogen.

And through the Pandemic we now see that these “prestigious” journals are not so all the time so prestigious.

Science is not simple.

This mesmerization with statistics gets us into the weeds.

Patients are told to be fearful and often miss out inappropriately.

Mercola wrongly writes yesterday:

This recent study is perhaps the most damaging piece of evidence I've encountered in the last five years that contradicts the claim that estrogen protects the brain.

No this study does not clearly show that to make such a harsh statement.

For shame on these scare tactics. Berkson

The research, published in one of the most prestigious medical journals, found that using pure estrogen receptor antagonists or aromatase inhibitors was associated with a lower risk of developing dementia across the entire expected female lifespan.

But this was only in women who just got a diagnosis of cancer. This changes everything! For shame. Berkson

What makes this study particularly significant is its use of "pure" anti-estrogen drugs. Previous studies showing protective effects against dementia often used selective estrogen receptor modulators (SERMs) like clomiphene, tamoxifen, or raloxifene. These drugs have anti-estrogenic effects in some tissues but are potent estrogens in others.

I work with these patients all the time.

Going on estrogen blockers often produces brain fog, severe joint pain, weight gain, and misery. We see this so often, it’s shocking to think those statistics showed women on estrogen blockers think better. We do not see this in practice!

What we see clinically does not validate what this not heavy science is suggesting.

There are confounding factors here at play that are NOT being discussed.

Also, it was a very weak hazard ratio.

This is not hard data.

This was not a definitive study showing without a doubt that estrogen is brain kryptonite.

And why is it that testosterone is okay for the brain, but not estrogen?

Both estrogen and testosterone signal to receptors in brain tissue.

Both hormones are highly part of keeping the volume of the hippocampus larger. So more memories are stored, while more are being made.

This is more scare tactics from questionable data.

That is not controlling for critical confounding variables. That is retrospective.

That is called NOT HARD data even by the original authors.

And also, older women were shown to be benefitted by estrogen replacement. That wasn’t discussed or teased apart.

This fear of estrogen, this supposed brain damaging effect, does not hold up when you look at patients clinically and see their response on balanced hormones.

And this study has huge confounding variable flaws.

On balanced hormone therapies, most of the time, most of people feel emotionally better. Think better. More like their younger selves.

Be very careful whose fear you let enter your cells and take residence.

Say NO to the inappropriate hormone fears!

Knowledge is power.

Be careful whose scare tactics you decide to be scared by.

Size matters.

You want your hippocampus voluptuous and signaling away.

What helps do this?

Estrogen in women.

Testosterone in men.

Dr. B.

Agile Thinking

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