Synthetic Hormones Are Not Bioidentical: Why the Women’s Health Initiative (WHI) Study Got It Wrong
If You Don't Understand This Difference, Nothing Else Makes Sense
Here's what you need to know: Women were scared away from hormone therapy for over 20 years because the WHI study used the wrong hormones entirely.
Not the hormones we use now. Not the hormones women's bodies even recognize. Not anything close to what modern bioidentical hormone therapy looks like.
The confusion between synthetic hormones and bioidentical hormones created decades of fear, suffering, and misinformation. And it's time to clear that up once and for all.
Let's break this down the way it should have been explained from the beginning: direct, clear, and honest.
The WHI Used Hormones That Were Never Meant for the Human Body
Here's where everything went wrong.
"They were using synthetic hormones, not bioidentical hormones that mimic natural physiology."
That alone should have stopped everyone from applying the WHI results to modern menopausal care. But it didn't.
Instead, synthetic hormones that don't behave like human hormones were treated as if they were equivalent to estradiol and real progesterone. They are not. And women paid the price for that confusion for over two decades.
The WHI studied two synthetic hormone preparations:
Premarin - conjugated equine (horse) estrogens
Provera (medroxyprogesterone acetate) - synthetic progestin
Neither of these resembles what your body naturally produces. Neither acts the way human hormones act. And neither is used in modern bioidentical hormone therapy.
Synthetic Estrogen: Horse-Derived and Stronger Than Anything Humans Produce
This part still shocks people when they hear it.
The WHI used Premarin—a horse-derived estrogen that contains multiple estrogens that are not made in the human body.
Let's sit with that for a second.
Premarin contains 17 different estrogens. The human body only produces 3 estrogens naturally (estradiol, estrone, and estriol). The other 14 estrogens in Premarin are foreign to human physiology.
These horse estrogens are:
Much stronger than human estrogens
Metabolized differently by the human liver
Processed differently by the vascular system
More stimulating to breast tissue than human estradiol
"It is insane to me that we thought it was okay to use Premarin on women and thought that that was the same thing as replacing estradiol."
Exactly. It's not the same thing. It never was.
Why This Matters for Breast Tissue
Premarin's stronger estrogens stimulate breast tissue much more aggressively than human estradiol. This is why the WHI saw increased breast cell proliferation—not because estrogen itself is dangerous, but because horse estrogen behaves differently in human tissue.
Modern bioidentical estradiol and estriol don't have the same aggressive stimulation effect. They work with your body's natural receptors in a physiologic way.
Synthetic Progestin: Shuts Down Progesterone Instead of Balancing Estrogen
Now let's talk about the other half of the hormone equation—because estrogen doesn't work alone. And this is where the WHI did the most damage.
The WHI used Provera—a synthetic progestin. It's not progesterone.
And here's the critical difference:
"It actually shuts off natural progesterone production."
What Happens When You Shut Down Progesterone
When you give synthetic progestin long-term, it blocks your body's own progesterone production. And when natural progesterone disappears, estrogen becomes unbalanced and unopposed.
When estrogen takes over without the protective effects of progesterone, that's when you see:
Increased cell growth in the breast
Increased uterine cell proliferation
Increased risk of estrogen-sensitive cancers
Increased clotting risk
Endothelial dysfunction (blood vessel damage)
Cardiovascular risk
"By blocking progesterone you're basically making estrogen take over… and that's not a good biologic process."
Synthetic Progestin Has Known Risks
Medroxyprogesterone acetate (Provera) has documented risks:
Increases breast cancer risk (because it doesn't balance estrogen properly)
Increases clotting factors
Causes blood vessel (endothelial) dysfunction
Blocks many of progesterone's protective effects
Doesn't support brain function the way real progesterone does
Doesn't help with sleep or anxiety like real progesterone
We know this because synthetic progestins are used in birth control pills. We've seen their effects over decades of use. They work for contraception (by shutting down natural progesterone), but they don't support physiology the way bioidentical progesterone does.
The hormones used in the WHI do not resemble modern hormone therapy at all.
Bioidentical Hormones Act Completely Differently
Now let's shift to what modern bioidentical hormone therapy actually uses.
Bioidentical hormones are structurally identical to the hormones your body already produces. They're not foreign molecules. They're not synthetic derivatives. They're the exact same molecular structure as human hormones.
This means:
Your body recognizes them
They bind to receptors correctly
They're metabolized the way your natural hormones are metabolized
They support physiology instead of disrupting it
Bioidentical Progesterone vs. Synthetic Progestin
"Bioidentical progesterone does none of these things. It literally just supplements and gives you back some natural progesterone."
Here's what bioidentical progesterone actually does:
✓ Supports the brain through GABA receptor stimulation (the highest concentration of progesterone receptors in your entire body is in your brain)
✓ Helps you sleep naturally by calming the nervous system
✓ Reduces anxiety without sedation
✓ Protects breast tissue by balancing estrogen's growth signals
✓ Reduces cancer risk in estrogen-sensitive tissues (breast, ovaries, uterus, colon)
✓ Improves insulin sensitivity and supports metabolism
✓ Supports muscle maintenance
✓ Works with your body, not against it
That's the exact opposite of synthetic progestin.
This is why the data from the WHI cannot be applied to bioidentical progesterone. They're completely different molecules with completely different effects.
Modern Estradiol Is Physiologic and Protective
Let's talk about the estrogens used in modern bioidentical hormone therapy.
The estrogens used safely and effectively are:
Estradiol (E2) - the primary estrogen your ovaries produced before menopause
Estriol (E3) - a weaker, protective estrogen
Both are human estrogens. Both are much milder than the horse estrogens in Premarin. And they have completely different effects on breast tissue, cardiovascular health, and bone density.
"We use estradiol and estriol… very moderate to weak estrogen. We don't use any estrone which was used in that old hormone therapy."
Why This Matters for Safety
Bioidentical hormone therapy focuses on estradiol and estriol—not estrone—which is why the safety profile is completely different from old synthetic hormone therapy. Estrone (E1) is the strongest human estrogen and is more common after menopause when it's produced from fat tissue. Higher estrone levels (especially from synthetic sources) are associated with increased cancer risk.
Using the bioidentical hormones of estradiol and estriol (and avoiding estrone) to:
Not overstimulate breast tissue
Support cardiovascular health when started early
Reduce inflammation instead of increasing it
Improve bone density
Support brain function and cognition
Maintain vaginal and urinary health
None of this resembles the WHI hormone protocol.
Delivery Method Matters: Why Oral Hormones Are Problematic
The WHI made another critical error: they only used oral estrogen.
"They only used oral estrogen… which increases clotting factors… raises triglycerides… increases inflammatory pathways… raises CRP."
Why Oral Estrogen Is Different
When you take estrogen orally, it goes through the liver first (called "first-pass metabolism"). This causes:
↑ Clotting factors (increased thrombosis risk)
↑ Triglycerides (worse lipid profile)
↑ Inflammatory markers (especially C-reactive protein/CRP)
↑ Blood pressure in some women
Modern Delivery Methods Avoid These Problems
Modern bioidentical hormone therapy uses delivery methods that bypass the liver:
For Estrogen:
Transdermal patches or creams (absorbed through skin)
Sublingual troches (dissolved under the tongue)
Vaginal estrogen (local application)
For Progesterone:
Transdermal creams
Sublingual troches
Oral micronized progesterone (which is processed differently than synthetic progestin)
"We do not see the same effect with sublingual or transdermal estrogens… They were not tested in the WHI study."
So again: The WHI findings cannot be applied to modern treatments. The hormones are different. The delivery is different. The physiology is different.
This Is Why the WHI Cannot Be Used to Judge Modern Hormone Therapy
Let's be crystal clear about what the WHI actually studied versus what modern therapy uses:
What the WHI Studied:
❌ Synthetic horse estrogen (Premarin)
❌ Synthetic progestin (Provera)
❌ Oral delivery only
❌ One-size-fits-all dosing
❌ Women aged 63+ (10-15 years post-menopause)
❌ Non-symptomatic women
❌ No individualized monitoring
What Modern Bioidentical HRT Uses:
✅ Human bioidentical estradiol and estriol
✅ Human bioidentical progesterone
✅ Transdermal, sublingual, or vaginal delivery
✅ Individualized dosing based on labs and symptoms
✅ Women during perimenopause/menopause (ages 40-60)
✅ Symptomatic women seeking relief
✅ Regular lab monitoring and dose adjustments
"Modern bioidentical hormone replacement therapy is not the same hormones. We are using physiologically the same hormones in much lower doses in different formulations."
This is the truth women were never told.
Why This Distinction Matters So Much
The WHI created 20+ years of fear by studying:
The wrong hormones
At the wrong doses
In the wrong population
At the wrong time
With the wrong delivery method
Then those results were applied to every woman considering hormone therapy, even though none of those factors matched modern treatment.
That's not science. That's overgeneralization that caused massive harm.
Women lost access to treatment that could have:
Prevented bone loss and fractures
Protected cognitive function
Reduced cardiovascular risk (when started early)
Improved quality of life dramatically
Supported metabolic health
Maintained vaginal and urinary health
All because synthetic hormones were incorrectly equated with bioidentical hormones.
What Modern Bioidentical Hormones Actually Do
"The hormones we use now are extremely beneficial."
And that's not an exaggeration. Here's what bioidentical estradiol and progesterone support:
Brain & Cognition:
Reduces brain fog
Supports memory and learning
Protects against cognitive decline
Supports neurotransmitter function
Increases mitochondrial energy production
Sleep & Mood:
Improves sleep quality (especially progesterone)
Reduces anxiety naturally
Stabilizes mood
Supports emotional regulation
Bone Health:
Decreases bone breakdown
Increases bone mineral density
Reduces fracture risk dramatically
Cardiovascular Health (when started early):
Improves endothelial function
Reduces arterial plaque formation
Improves lipid profiles (lowers LDL, raises HDL)
Reduces systemic inflammation
Metabolic Health:
Improves insulin sensitivity
Supports healthy fat distribution
Helps maintain muscle mass
Supports mitochondrial function
Sexual & Genitourinary Health:
Maintains vaginal tissue thickness and lubrication
Reduces painful intercourse
Reduces recurrent UTIs and yeast infections
Supports libido
Skin, Hair & Connective Tissue:
Improves collagen production
Increases skin elasticity and thickness
Reduces hair thinning
Supports joint health
Overall Quality of Life:
Reduces hot flashes and night sweats
Improves energy levels
Enhances sense of well-being
Supports ability to exercise and build strength
Women need to know the truth. Women deserve better than the confusion and fear created by the WHI.
The FDA (Food and Drug Administration) Finally Acknowledged the Difference
After more than 20 years, the FDA removed the black box warning from estradiol—not from synthetic estrogens, but from human bioidentical estradiol.
Why? Because they finally acknowledged what functional medicine providers have been saying for years: bioidentical estradiol is not the same as conjugated equine estrogens.
This is historic. This is validation. And this opens the door for better, more accurate conversations about hormone therapy.
Final Thoughts: You Cannot Compare Them
You cannot compare estradiol and bioidentical progesterone to horse estrogen and synthetic progestin.
They are not the same molecules. They do not act the same way. They do not have the same risks or benefits.
That's why the old WHI data never made sense. That's why women and their doctors felt confused for decades. That's why the FDA finally removed the black box warning. And that's why millions of women can finally get relief without outdated fear.
"This is a major opportunity for you guys to look at your own body, how you're feeling… You do not have to live with those things."
Women deserve clarity. Women deserve options. Women deserve accurate information about what modern bioidentical hormone therapy actually is—not what it was incorrectly compared to 20+ years ago.
If you're experiencing symptoms of perimenopause or menopause, you deserve to know that safe, effective, physiologic treatment options exist. You deserve a provider who understands the difference between synthetic and bioidentical hormones. You deserve informed consent based on current science, not outdated fear.
Ready to Learn More?
Watch the full video where I break down the difference between synthetic and bioidentical hormones in detail
Download the free patient handout with everything you need to know about modern hormone therapy
Read the full blog series on the WHI study flaws and the FDA's reversal
Follow Dr. Lori on social for real talk about women's health and hormone education
Schedule a consultation to discuss your symptoms and whether bioidentical hormone therapy is right for you
The science is clear. The confusion ends here!
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