The Problem with Oral Estrogens: Everything You Need to Know - Birth Control , Hormone Therapy, and others.

Birth Control, HRT, and others

Proper and safer Hormone Therapy. Why do I talk about this so much?

My goal here is to help you understand what you're putting into your body so you can make informed decisions. I’m not against the use of estrogens in hormone therapy — the key point is that the route of administration matters and can completely change how your body reacts. Oral estrogens are widely used in birth control, hormone replacement therapy (HRT), and for treating conditions like menstrual disorders and menopause. But let’s break down what this really means for your health.

Oral Estrogens: Why Do They Need to Be Modified to Work?

If you ingest a natural estrogen like estradiol, it gets destroyed by stomach acid before it can be absorbed. To survive the digestive process, it’s chemically modified. The most common forms are:

• Ethinylestradiol: found in birth control pills.

• Conjugated estrogens: used in HRT.

These modifications make the hormone more stable but also much more potent when it passes through the liver — and that’s where things get complex.

What Happens in the Liver: Metabolization and Metabolites

Once oral estrogen is absorbed, it passes through the liver (first-pass metabolism) before entering the bloodstream. During this process, it’s broken down into different metabolites:

• 2-hydroxyestrone (2-OH-E1): known as the “protective” metabolite due to its antioxidant properties.

• 4-hydroxyestrone (4-OH-E1): a metabolite with pro-oxidant effects that can increase oxidative stress.

• 16α-hydroxyestrone (16α-OH-E1): a proliferative metabolite that promotes cell growth and contributes to inflammation.

Why does this matter? An increase in 16α-hydroxyestrone production is associated with a higher risk of endometrial hyperplasia and chronic inflammation.

Coagulation and Blood Clot Risk: What Does Oral Estrogen Do to Your Blood?

When the liver processes oral estrogens, it increases the production of proteins involved in blood clotting, such as:

• Fibrinogen

• Factor VII and Factor VIII (key players in coagulation)

• C-reactive protein (CRP) (an inflammatory marker)

The issue? This thickens the blood and raises the risk of clot formation, especially for women with a genetic predisposition.

Factor V Leiden:

Women with this common genetic mutation have difficulty “turning off” the clotting process, making them more prone to developing blood clots when using oral estrogens.

How Oral Estrogens Affect Your Cholesterol Levels

The liver also regulates fat metabolism during estrogen breakdown. As a result, oral estrogens can:

• Increase triglycerides

• Lower HDL (“good” cholesterol) in some women

• In some cases, increase HDL levels depending on the type of progestin used.

Additionally, higher levels of 16α-hydroxyestrone are linked to increased inflammation and oxidative stress, further worsening lipid profiles.

SHBG: Why Estrogen “Binds” Your Hormones

SHBG (sex hormone-binding globulin) is a protein produced by the liver that binds to hormones like testosterone, estradiol, and DHT, controlling how much is available for your body to use.

What happens with oral estrogens? They significantly increase SHBG production, which:

• Reduces free testosterone levels (essential for libido, energy, and muscle strength).

• Can lead to fatigue, low drive, and difficulty maintaining muscle mass.

Liver Overload and Increased Inflammation

The liver works overtime to metabolize oral estrogens, releasing enzymes and inflammatory markers during the process.

Potential consequences:

• Increased liver enzymes (ALT, AST, GGT)

• Elevated CRP, indicating systemic inflammation.

• Increased VLDL production, a lipoprotein that carries triglycerides.

For women with a history of insulin resistance or liver conditions, this can exacerbate metabolic issues.

The Impact of Oral Estrogens on Other Hormones

The liver doesn’t just metabolize estrogen — it also processes other key hormones like progesterone, testosterone, and DHEA. Oral estrogen stimulates the production of enzymes from the CYP450 family, which speeds up the breakdown of these hormones.

What this can lead to:

• Lower progesterone levels, causing an imbalance with estrogen (also known as estrogen dominance).

• Decreased free testosterone, affecting energy, strength, and libido.

• Impaired DHEA conversion, making it harder for the body to produce other hormones derived from this precursor.

Common symptoms:

• Intense PMS

• Difficulty gaining or maintaining muscle mass

• Mood swings and constant fatigue

Oral Estrogen and Your Gut: A Complicated Relationship

After being metabolized in the liver, part of the estrogen is excreted via bile into the intestines. Here’s where it gets tricky: some of the metabolites can be reabsorbed with the help of an enzyme produced by gut bacteria, called beta-glucuronidase.

Potential issues:

• Microbiome imbalance, promoting the growth of inflammatory bacteria.

• Re-circulation of estrogens, leading to higher levels of free estrogen in the body.

• Increased intestinal permeability (“leaky gut”), which contributes to systemic inflammation and can worsen autoimmune conditions.

Practical Consequences

• Gut dysbiosis: an overgrowth of harmful bacteria.

• Worsened PMS and endometriosis symptoms: due to elevated free estrogen levels.

Chronic inflammation: which can contribute to insulin resistance and abdominal fat gain.

Are There Safer Alternatives?

Yes! Transdermal estrogens (gels, patches, creams) are absorbed through the skin and enter the bloodstream directly, bypassing the liver. This reduces the impact on coagulation, SHBG, and lipid metabolism.

Why Does the Route of Administration Matter?

Because you can manage your symptoms and maintain hormonal balance without overloading your liver and gut.

Conclusion: Before starting or continuing the use of oral estrogens, talk to your doctor and evaluate whether it’s the best option for you.

Did you already know that the route of administration makes such a big difference? Let me know in the comments!

References and Sources:

1. Scientific articles on hormone metabolism and oral estrogens: PubMed.gov

2. Clinical guidelines for hormone replacement therapy: Endocrine Society's Clinical Practice Guidelines

3. Information on coagulation and genetic predispositions: National Library of Medicine resources

4. Studies on gut microbiome and hormone reabsorption: Research articles from journals like Nature and Gut Microbes

5. Insights into lipid profiles and hormonal impacts: American Heart Association reports

6. Endocrinology and metabolism reviews: Society for Women’s Health Research reports and medical journals on estrogen pathways.