If you're on HRT, dosage isn't the only question that matters — how well your body clears and metabolizes that estrogen matters too. In this episode, Karen Martel talks with David Roberts and John Gilday of Mara Labs about estrogen metabolism, receptors, xenoestrogens, and detoxification pathways, and why "estrogen dominance" is often more nuanced than it sounds.

If you're taking HRT, it's not enough to only ask how much estrogen you're using. You also have to ask a second question: how well is your body actually processing and clearing that estrogen?

In this episode, I sit down with David Roberts and John Gilday from Mara Labs to unpack estrogen metabolism, estrogen receptors, environmental hormone disruptors, and detoxification pathways — and why the conversation around "estrogen dominance" is often way too simplistic. We talk about the difference between having high estrogen and having estrogen that isn't being metabolized efficiently, especially in perimenopause, when estrogen can fluctuate wildly while progesterone starts dropping.

We also get into xenoestrogens, microplastics, estrogen metabolites, and the body's phase one, phase two, and phase three detoxification pathways — along with why compounds like sulforaphane, resveratrol, black cohosh, and curcumin have become such a point of interest in midlife health conversations.

The big message here: hormone optimization isn't always about adding more. Sometimes it's about making sure your body has the tools it needs to use, metabolize, and eliminate hormones effectively.

 

In This Episode, We Discuss

• What "estrogen dominance" can actually mean in perimenopause
• Why low progesterone can change the way estrogen affects the body
• Estrogen receptor alpha versus estrogen receptor beta
• How xenoestrogens and endocrine-disrupting chemicals may interfere with hormonal signaling
• Why estrogen metabolism matters whether your estrogen is natural or coming from HRT
• Phase one, phase two, and phase three detoxification explained
• Why genetics may affect how efficiently women metabolize estrogen
• What sulforaphane is and why broccoli sprouts get so much attention
• Sulforaphane vs. DIM for estrogen metabolism
• The roles of resveratrol, black cohosh, carnosic acid, and curcumin
• Why inflammation, oxidative stress, and detoxification are all connected
• How supplements may fit into a broader midlife hormone strategy

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Key Takeaways

• "Estrogen dominance" isn't always about having too much estrogen. It can also reflect estrogen relative to progesterone, or estrogen that isn't being metabolized and cleared efficiently.
• If you're on HRT, clearance matters as much as dosage. The body has to metabolize and eliminate estrogen through the same pathways whether it's naturally produced or introduced through therapy.
• Not all estrogen receptors behave the same way. Estrogen receptor alpha and beta can have different effects in different tissues, which helps explain estrogen's wide-ranging impact throughout the body.
• Everyday environmental exposures may add to your estrogenic load. Xenoestrogens from plastics and other sources can interact with estrogen receptors independently of your own hormone levels.
• Detoxification happens in three phases. Supporting phase one, two, and three processes — not just one — may be relevant for efficient estrogen metabolism.
• Genetics can influence how efficiently you metabolize estrogen, which may help explain why women respond differently to the same HRT dose.
• Compounds like sulforaphane, DIM, resveratrol, black cohosh, and curcumin are supportive tools, not stand-alone solutions. They work best as part of a broader, personalized hormone strategy.

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5. Frequently Asked Questions

What does "estrogen dominance" actually mean?

Estrogen dominance doesn't always mean your estrogen level is too high — it can also mean estrogen is elevated relative to progesterone, or that your body isn't metabolizing and clearing estrogen efficiently. In perimenopause, fluctuating estrogen alongside declining progesterone can create this relative imbalance even when lab values look normal.

Is estrogen dominance normal during perimenopause?

A relative shift toward more estrogen influence — often because progesterone is dropping faster than estrogen — is a common pattern during perimenopause. This doesn't mean every woman experiences it the same way, and symptoms can vary widely depending on individual hormone levels and metabolism.

Does taking HRT mean I don't need to worry about estrogen metabolism?

No — estrogen from HRT still has to be metabolized and cleared through the same detoxification pathways as naturally produced estrogen. Supporting those pathways can be relevant for women on HRT, not just for women managing naturally elevated estrogen.

What are phase one, phase two, and phase three detoxification?

These refer to the stages the body uses to process and eliminate estrogen: phase one converts estrogen into intermediate metabolites, phase two attaches molecules to make those metabolites easier to eliminate, and phase three transports them out of the body. When one phase isn't working efficiently, it may affect how well estrogen is cleared overall.

What's the difference between sulforaphane and DIM?

Sulforaphane is a compound found in broccoli sprouts, while DIM (diindolylmethane) comes from cruciferous vegetables more broadly, and both are discussed for their potential role in supporting estrogen metabolism pathways. They aren't interchangeable, and how each is best used can depend on an individual's specific needs — this is a good topic to discuss with a knowledgeable practitioner.

Can supplements alone fix estrogen dominance?

Supplements like sulforaphane, DIM, resveratrol, black cohosh, and curcumin may support the body's detoxification and metabolism pathways, but they aren't presented as a stand-alone fix. They tend to work best as part of a broader strategy that also considers hormone levels, lifestyle factors, and individualized testing.

Should I get my estrogen metabolism tested?

If you're experiencing symptoms that don't seem to line up with your standard hormone lab results, testing that looks at estrogen metabolites specifically may provide more insight than a standard estrogen level alone. This is a conversation worth having with a provider familiar with hormone metabolism testing.

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