Why Estrogen Behaves Differently After 45 — And How Your Genes Shape the Experience

If your sleep feels lighter, your mood responds differently to stress, hot flashes seem unpredictable, or foods and supplements affect you in new ways, this episode helps explain what’s happening.

This episode explores how estrogen behaves after 45 — not simply as a hormone that declines, but as one that shifts roles — and why genetics play a key role in how those changes are experienced.

You’ll learn how:

• Estrogen influences more than reproduction, including inflammation, glucose balance, circulation, and stress response
• Hormone shifts change how receptors, detox pathways, and cortisol interact after 45
• Three key biological shifts make hormone patterns feel more noticeable in midlife
• Genes like ESR2, CYP1B1, SHBG, and COMT shape sensitivity, stability, and stress tolerance
• Simple, consistent foundations support estrogen metabolism and hormone balance without extremes

This episode is especially helpful if you’ve noticed fluctuating energy, changing stress tolerance, mixed hormone signals, or increased sensitivity to foods, supplements, or environmental triggers after 45.

To learn more about the work behind this podcast, visit inspiredlivingforwomen.com

Are you new to genomics?

Click Here to get your free guide, Genetics vs. Genomics: They Aren’t the Same Thing, to understand how genetic data becomes meaningful insight and why interpretation matters more than testing alone after 45.

This podcast is for educational purposes only and is not intended to diagnose, treat, or provide medical advice. The information shared reflects general biological and genetic principles. Always consult a qualified healthcare professional regarding your own health decisions.

Transcript

0:00
Intro Music
Your Genes by Design Podcast with Lauri Wakefield

00:31 — Welcome And Series Context
Perimenopause Begins and Why It Varies

Hi, I’m Lauri. Thanks so much for joining me today.

In this episode, we’re shifting to a topic that every woman moves through, and it begins in perimenopause.

This is the stage of life when estrogen levels start to change — not always dropping right away, but becoming more unpredictable over time. And that experience can look very different from one woman to the next.

Some women feel calmer, clearer, and more stable as estrogen drops. Other women feel more wired, more inflamed, and more sensitive to stress. Many women experience both, sometimes within the same week.

Your genes have a lot to do with why.

Today, we’re going to look at how estrogen behaves after 45 and how genes like ESR2, also called estrogen receptor beta, CYP1B1, SHBG, and COMT help shape those patterns.

1:37 — Estrogen’s Wider Role in the Body

If you’ve ever wondered why your sleep feels lighter, your mood responds differently to stress, hot flashes come and go without warning, your energy feels unpredictable, or certain foods or supplements hit harder than they used to, it’s because estrogen is no longer doing the same jobs it once did.

Estrogen isn’t just a reproductive hormone. It also shapes cognition, inflammation, glucose balance, fat storage, circulation, and even how your body handles stress.

When estrogen levels change, other systems respond — and your genes influence how noticeable or disruptive those changes feel.

What’s really happening is that the way your receptors respond becomes more visible. The way you metabolize estrogen and the way you clear stress metabolites also become more noticeable once estrogen shifts.

2:49 — Three Shifts After Forty-Five

The reason this matters after 45 is that estrogen doesn’t disappear — but the way your body uses it changes.

What becomes more important isn’t just the amount of estrogen you have, but the type of estrogen and the pathways your body tends to favor.

There are three things that start to matter more after the age of forty-five.

First, receptor sensitivity shifts — especially ESR2, or estrogen receptor beta. These receptors play a major role in breast health, bone health, and inflammation.

Second, detox pathways do more work. Lower estrogen doesn’t mean estrogen-related risk disappears. How efficiently you clear estrogen matters more than levels alone.

And third, stress becomes a bigger player. Estrogen normally helps buffer your cortisol response. When estrogen drops, cortisol’s influence becomes stronger, which is why stress feels different after forty-five.

This is one reason women can experience low-estrogen symptoms and estrogen-dominant symptoms at the same time. It might sound contradictory, but it’s simply how the body operates during this stage of life.

3:40 — Key Genes Shaping Hormone Patterns

Let’s look at some of the key genes that shape hormone patterns.

ESR2, or estrogen receptor beta, influences how sensitive your cells are to estrogen. Some variants are associated with stronger anti-inflammatory and anti-proliferative signaling, especially in breast and cardiovascular tissue. Other variants may mean you need more support from foods rich in phytoestrogens, fiber, and antioxidants.

If you carry a more protective ESR2 variant, you may experience fewer dramatic hormone swings or recover more quickly when they happen.

The second gene is CYP1B1. This is part of phase one estrogen metabolism, specifically the 4-hydroxylation pathway.

Certain variants can slow this pathway, which may increase sensitivity to environmental estrogens, certain fragrances, alcohol, and even high-dose biotin. This gene also influences how well your body responds to cruciferous vegetables and polyphenols that support estrogen processing.

Many women with CYP1B1 variants notice they’re more sensitive than they used to be — and that often reflects how estrogen metabolism changes after 45.

4:40 - SHBG Gene

The third gene is SHBG, or sex hormone-binding globulin. This one is often overlooked.

SHBG helps determine how much estrogen and androgens are free and available versus bound. It reflects how hormones are regulated and transported through the body.

Some variants naturally support more balanced hormone availability. When SHBG is supportive, many women feel more stable during hormonal transitions.

The final gene is COMT. COMT plays a role in phase two estrogen metabolism, clearing one branch of estrogen metabolites. It also helps clear stress metabolites like adrenaline.

If you have a slower COMT type, stress may feel more intense during hormonal shifts. If you have a faster COMT type, you may need more nutritional support, such as magnesium or B vitamins, to keep things steady.

This gene often explains why your experience feels the way it does.

Tests like the DUTCH test can show how these pathways are behaving in the body — but your genes help explain why they behave that way.

They provide the context behind the patterns.

5:50
Personalized Steps for Support

So what can you do to support your design?

Knowing your genetic variants helps personalize the foundations, because each pathway can need something slightly different.

A few grounded steps can make a noticeable difference.

Supporting estrogen metabolism consistently matters. Cruciferous vegetables, citrus, berries, fiber, and polyphenols help CYP1B1 move estrogen through preferred pathways.

Prioritizing stress regulation is key. If you have a slower COMT type, shorter fasting windows, consistent meals, lighter morning activity, and magnesium can create more stability.

Focusing on ESR2-supportive foods such as flaxseed, sesame, green tea, berries, and leafy greens helps support healthy estrogen receptor signaling.

And paying attention to SHBG patterns matters too. Steady protein intake, fiber, and omega-3s help keep hormone availability balanced.

One thing to remember is that estrogen doesn’t disappear. The way your body uses it changes.

6:44
Closing and Resources

That’s going to wrap things up for this episode.

If this episode helped you understand your experience a little better, follow this podcast and share it with other women who might benefit.

If you’re new to genomics, you might be interested in the free guide Genetics vs. Genomics: They’re Not the Same Thing. You’ll find a link in the show notes.

And if you’d like to learn more about me or the work I do, you can visit my website at inspiredlivingforwomen.com.

Thanks again for joining me, and have a great day.