The Hormone Hierarchy

You’ve heard the buzz about bioidentical hormones. Maybe your symptoms—crushing fatigue, weight gain, brain fog, vanishing libido—have sent you searching for answers. And somewhere along the way, someone mentioned hormone replacement therapy.

Here’s what most practitioners won’t tell you: simply replacing deficient hormones rarely solves the problem.

Recently, I sat down with my colleague Dr. Christian Jenski to discuss what we’re both seeing in our practices—a troubling trend where even in the integrative and functional medicine world, practitioners are doing hormone replacement rather than hormone optimization.

After treating thousands of patients over 25 years, I’ve learned that hormone optimization isn’t about throwing estrogen, progesterone, or testosterone at symptoms and hoping for improvement.

It’s about understanding your body’s hormone hierarchy—and respecting it.

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The Women’s Health Initiative: A Quarter Century of Confusion

Before we dive into hormone hierarchy, let’s address the elephant in the room. For nearly 25 years, women have been terrified of hormone therapy thanks to a deeply flawed study.

Dr. Jenski explained it perfectly: “The Women’s Health Initiative was actually run by a cardiologist, and the cardiologist’s goal was to determine if hormone replacement therapy decreased cardiovascular risk in women. And the average age of the woman in that study was 65. So just by that demographic alone, you knew the study results were gonna be skewed.”

During the study, the synthetic progestin arm showed a slight uptick in breast cancer. “And so this person came out and said, all hormones cause cancer. And everybody believed them and generations of women had their hormones taken away or were not offered hormones.”

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“So this person came out and said all hormones cause cancer. And everybody believed them and generations of women had their hormones taken away…”

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Here’s what they didn’t tell you: the study used synthetic hormones (Premarin and Provera), oral administration that increases clotting risk, and participants were often smokers. As I pointed out in our discussion, “There was a significant number of the females who were smokers, which we know hormones and smoking do not mix.”

By 2019, researchers quietly walked it back.

They acknowledged that bioidentical hormones, properly administered, may actually be protective. Some research even suggests women diagnosed with breast cancer while on bioidentical hormones have less aggressive disease.

But the damage was done.

As Dr. Jenski put it: “Generations of women were told their hormones were gonna kill you. Don’t use ’em.” It took six years after 2019 for them to say, “Just kidding. We were wrong… So sorry for all of the damage that you all have suffered.”

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Hormone Replacement vs. Hormone Optimization: What’s the Difference?

When I asked Dr. Jenski to define optimization, he explained: “Hormone replacement is… you have a deficiency and we’re giving you some back … and for a very few select individuals, you just give them back that hormone and all is right. Usually it’s a bit more complicated than that.”

Hormone optimization addresses the entire system. As Dr. Jenski described it: “Optimization is how that hormone is being utilized, processed, metabolized by the body. So things like the gut are involved. Things like the influence of these endocrine loops are involved. The autonomic nervous system or neurologic system in general is involved… there’s so many layers that might affect the way in which this person feels when they use hormones or not.”

Think of it this way: replacement therapy hands you a deficient hormone and says “here’s what you’re missing.” Optimization ensures your body can actually use what you’re giving it.

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Understanding the Hormone Hierarchy

Not all hormones carry equal weight. Your body has priorities, and understanding them is essential for effective treatment.

Primary Hormones: The Survival Trio

1. Cortisol (The Adrenal Hormone)

Cortisol is king. Produced by your adrenal glands in response to stress, cortisol regulates blood sugar, blood pressure, immune function, and inflammation. Without it, you die. Period.

Signs of cortisol imbalance include:

• Waking between 2–4 AM unable to fall back asleep
• Crashing energy in the afternoon
• Difficulty recovering from exercise
• Weight gain around your midsection
• Feeling “tired but wired”

For a deeper dive into cortisol’s role, read our comprehensive guide: Cortisol: The King of All Hormones.

2. Insulin (The Metabolic Master)

Here’s a statistic that should alarm you: roughly 80% of Americans show signs of insulin resistance.

Insulin resistance drives:

• PCOS and elevated testosterone in women
• Increased fat storage (especially abdominal)
• Chronic inflammation
• Accelerated aging
• Higher risk of diabetes, heart disease, and dementia

Your optimal hemoglobin A1C should be under 5.0. Most conventional doctors won’t flag concern until you’re over 5.7. That’s the difference between optimal function and metabolic dysfunction.

Learn more about fixing insulin resistance in our article on Insulin: Our Sticky Problem.

3. Thyroid (The Metabolic Conductor)

Your thyroid orchestrates metabolism at the cellular level. As Dr. Jenski pointed out: “Thyroid receptors don’t work without vitamin D and A.”

Yet most doctors only check TSH (thyroid stimulating hormone). That’s like judging a symphony based solely on whether the conductor showed up, without listening to the music.

A complete thyroid panel includes:

• TSH
• Free T4
• Free T3
• Reverse T3
• Thyroid antibodies (anti-TPO and anti-TG)

For the full story on thyroid function, see Thyroid: The Conductor of Your Hormone Symphony.

Secondary Hormones: The Supporting Cast

Only after your primary hormones are balanced should we address sex hormones:

• Estrogen — Learn about its functions in Estrogen: The Younger Sister
• Progesterone — Discover why it matters in Progesterone: The Elder Sister
• Testosterone — Understand its role in Testosterone in Women’s Health

What is critical to understand, is that you cannot adequately address the secondary hormones until you have addressed your primary hormones. While sex hormones are important for sexual development and healthy, vibrant living, they are not essential for life itself. Insulin, cortisol, and thyroid hormone are the critical factors to focus on first.

The Fourth Factor: Your Autonomic Nervous System

Dr. Jenski brought up a critical point that often gets overlooked: “The autonomic nervous system or neurologic system in general is involved.”

I elaborated: “When someone’s in sympathetic overdrive, they have trauma… when that’s really elevated, those are the people who do really poorly when I start messing with the hormones if I have not addressed that stuff first.”

Conditions like POTS, mast cell activation syndrome, and hypermobility often overlap with hormone imbalances. If these aren’t addressed, hormone therapy alone won’t provide lasting relief.

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Why Gut Health Can’t Be Ignored

Here’s something most practitioners miss: your gut is where sex hormones go to be detoxified.

Your liver processes estrogen through two phases of detoxification, packages it for elimination, and sends it to your gut. Your gut microbiome determines whether that estrogen gets eliminated or reactivated.

For women with PCOS, perimenopause, or any hormone imbalance, addressing gut health isn’t optional—it’s foundational. Read more in our articles on PCOS in Young Women and Hormones After 40.

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Nutrient Deficiencies: The Missing Piece

As I mentioned to Dr. Jenski: “If your vitamin D level’s low, if your magnesium’s low, if your potassium’s low… how are hormones gonna work without magnesium and calcium being balanced?”

I’ve also observed something fascinating about hypermobile patients (approximately 20% of the population): “If you’re hypermobile, all of a sudden you’re gonna have a tendency towards deficiencies in a lot of amino acids, vitamin C, trace minerals and you tend to have low vitamin D levels.”

This is why optimization requires addressing nutritional status before—or alongside—hormone supplementation.

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The Right Order of Operations

Based on our extensive discussion, here’s the proper sequence for hormone optimization:

1. Address Stress and the Autonomic Nervous System
– Implement stress-reduction techniques
– Support vagal tone
– Address trauma if present

2. Optimize Metabolic Health
– Improve insulin sensitivity
– Ensure adequate vitamin D (critical for insulin receptors)
– Address inflammation

3. Support Thyroid and Adrenal Function
– Provide necessary nutrients (iodine, selenium, zinc, tyrosine, magnesium, B vitamins)
– Use botanical support when appropriate

4. Heal the Gut and Detoxification Pathways
– Restore healthy gut microbiome
– Support liver detoxification
– Ensure regular bowel movements

5. Balance Sex Hormones
– Test comprehensively
– Use bioidentical hormones when needed
– Apply topically (never oral estrogen)

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Life Stage Considerations

As I explained in our conversation, your approach should match where you are in life:

Ages 20–35: “If you’re 20, 25, you haven’t had any kids, you should be able to fix your hormone issues without hormone replacement. It becomes an issue of what’s going on in your gut. Stress, sleep, cortisol issues, you know, trauma, sleep, wake cycles, what’s your diet look like?”

Ages 30–45: “There’s a span from 30-ish to early forties where… testosterone levels will start to come down a little bit initially. A little later, progesterone will start to dip while estrogen is maintained.”

Perimenopause: Dr. Jenski called this phase “a moving target,” explaining that “you’re just kind of supporting that area and when it’s high, really ramp up detox and then catch it right as it’s on its way out.”

Menopause and Beyond: This is when replacement becomes straightforward. And here’s critical information: there’s no age limit on hormone optimization. As I told Dr. Jenski: “Estrogen is directly related to maintenance of your hippocampus, which is where your memory is… it’s also related with cerebral volume… Would you want to maintain that health advantage that estrogen gives you? Yes.”

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The Path Forward

As Dr. Jenski summarized: “Optimization can be a little bit generalized… but it always has to be personalized and it depends on parameters, clinical correlation, and where you are within normal.”

You deserve more than hormone replacement. You deserve optimization.

In the next article in this series, we’ll explore how your gut and nervous system influence hormone balance in ways most practitioners never consider. We’ll discuss practical strategies for supporting these critical systems and why environmental toxin exposure may be sabotaging your hormone therapy.

Read Next: Your Gut & Nervous System: The Hidden Hormone Influencers (Coming Soon)

Want to dive deeper into specific hormones? Explore our comprehensive hormone library:

• Cortisol: The King of All Hormones
• Insulin: Our Sticky Problem
• Thyroid: The Conductor
• Estrogen: The Younger Sister
• Progesterone: The Elder Sister
• CIRS vs Hypothyroid

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This article is part of a four-part series based on conversations between Dr. Aaron Hartman and Dr. Christian Jenski about hormone optimization. The information provided is for educational purposes and should not replace personalized medical advice from your healthcare provider.