Hans' Substack

Hans' Substack

Share this post

Hans' Substack
Hans' Substack
Lowering estrogen, gut focused

Lowering estrogen, gut focused

The Gut-Based Protocol That Took Me from 90 pg/mL to <25

Hans's avatar
Hans
Jul 11, 2025
∙ Paid
7

Share this post

Hans' Substack
Hans' Substack
Lowering estrogen, gut focused
5
4
Share

Before we dive into how to lower estrogen through the gut, it's important to understand what drives estrogen up in the first place, especially in men. Most people blame high estrogen on genetics or age, but in reality, it’s often the result of chronic inflammation, liver dysfunction, poor bile flow, and microbiome imbalance.

Here are the major contributors:

1. Aromatase Activation

Aromatase - an overview | ScienceDirect Topics

Aromatase is the enzyme that converts testosterone into estrogen. When it’s overactive, estrogen rises while testosterone drops, causing a double hit to your hormonal balance.

What increases aromatase?

  • Endotoxin (LPS) – Produced by gram-negative bacteria in the gut. A major trigger of inflammation and aromatase expression.

  • Inflammation – IL-6, TNF-α, and other inflammatory cytokines upregulate aromatase.

  • Cortisol – Chronic stress raises cortisol, which promotes aromatase.

  • Histamine – High histamine levels (often from gut-derived mast cell activation) can increase aromatase, shown clearly in women, and likely in men too (R).

  • Nutritional deficiencies – Zinc, magnesium, selenium, and vitamin D all play a role in suppressing aromatase. Deficiencies remove this brake.

  • Low T3 (thyroid hormone) – T3 suppresses aromatase, so hypothyroid men often have a high estrogen-to-testosterone ratio despite “normal” labs.

If your inflammation is high and your T3 is low, your testosterone will get hijacked and converted to estrogen.

2. Poor Estrogen Detoxification via the Liver

null

Your liver is responsible for metabolizing and clearing estrogen. This involves two main steps:

Phase I:

  • Enzymes like CYP1A1 and CYP1B1 convert estrogen into intermediate metabolites (e.g., 2-OH-E1, 4-OH-E1).

Phase II:

  • These intermediates are conjugated (methylated, sulfated, or glucuronidated) into water-soluble forms and sent out via urine or bile.

If your liver lacks the necessary enzymes, nutrients, or energy, this system backs up. This leads to a build-up of:

  • More potent estrogens (like estradiol)

  • Toxic intermediates (like 4-OH-E1 and 16-OH-E1)

  • Estrogen dominance symptoms

Without proper liver support, even normal estrogen levels can cause problems due to poor clearance.

3. Insulin Resistance

Insulin resistance promotes estrogen dominance in several ways:

  • Increases aromatase activity in fat tissue

  • Reduces SHBG, increasing free estrogen

  • Worsens liver detox (since insulin resistance promotes fatty liver)

And what’s one of the key drivers of insulin resistance?

👉 Endotoxin.

Endotoxin promotes:

  • Liver inflammation (via Kupffer cell activation)

  • Hepatic insulin resistance

  • Fatty liver (NAFLD)

  • Inflammation-driven estrogen buildup

Studies show that just a small rise in LPS levels can cause a rapid increase in:

  • Liver TNF-α

  • Hepatic fat accumulation

  • Aromatase activity

So if your gut is inflamed and leaking LPS into your liver via the portal vein, your estrogen will climb—even if your testosterone production is solid.

4. Poor Bile Flow

Once your liver detoxifies estrogen, it sends it into the bile for elimination. If bile flow is sluggish:

  • Estrogen stays stuck and gets reabsorbed in the intestines

  • Bile’s antimicrobial action drops → gram-negative bacteria overgrow

  • This creates a vicious cycle of more LPS, more inflammation, more aromatase

Bile is the body’s waste chute. If it clogs up, estrogen builds up fast.

5. Beta-Glucuronidase Overactivity

null

Even when your liver does everything right, certain bacteria can sabotage the process.

Beta-glucuronidase breaks the glucuronic acid bond on conjugated estrogen, allowing it to re-enter your bloodstream.

It’s highest in:

  • Dysbiosis

  • Constipation

  • Low-fiber diets

  • Inflammation-driven microbiome shifts

This enzyme silently blocks detox and keeps estrogen circulating longer than it should.

Now let’s discuss how to optimize each of these in depth.

Hans' Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.

This post is for paid subscribers

Already a paid subscriber? Sign in
© 2025 Hans
Privacy ∙ Terms ∙ Collection notice
Start writingGet the app
Substack is the home for great culture

Share