Why do too much and too little estrogen feel the same?
In your 40s you start skipping ovulation. On those months you make almost no progesterone, while estrogen keeps swinging. So estrogen runs without its counterweight, which causes trouble without ever being high. Other months it drops out from under you. Bad sleep, anxiety, brain fog, fatigue, low sex drive and mood swings happen at both ends.
Your genes decide how well you receive estrogen and how fast you clear it. That is the part a blood test cannot see, and the part a genetic test can.
The printable guide for this.
Six pages, written for someone who has never heard any of this before. The gene table, the symptom chart, what to do on your own, what to ask me about first, and the red flags that need a doctor. Free, no email required.
Estrogen has to get in, and it has to get out.
Think of estrogen as a message.
For the message to do anything, something has to pick it up. Your cells have receptors, which work like a lock the message fits into.
Once the message is delivered, your body has to get rid of it. Your liver breaks it down and wraps it up. Your gut carries it out.
So there are two places things go wrong. How well you pick up the signal. And how well you clear out what is left behind.
Your genes affect both. That is the reason you and your sister can go through the same transition and have completely different years.
A blood test tells you how much estrogen was floating around on the morning you got stuck. It does not tell you how well your body receives it, or how fast you clear it. Those parts are written into you, and they do not change month to month.
Too much and too little feel the same.
Every month you ovulate, what is left behind makes progesterone. Progesterone balances estrogen out.
In your 40s you start skipping ovulation. On those months you make almost no progesterone, while estrogen keeps swinging.
So estrogen ends up running without its counterweight. It does not have to be high to cause trouble. It just has to be unbalanced.
Other months, estrogen drops out from under you. Same woman, same year, opposite problem.
Same symptom, two different causes
| When estrogen is high or unbalanced | Either way | When estrogen is low |
|---|---|---|
| Heavy or long periods Sore, swollen breasts Bloating Worse PMS Headaches before your period |
Bad sleep Anxiety, irritability Brain fog Fatigue Low sex drive Mood swings |
Hot flashes, night sweats Vaginal dryness Pain with sex Skipped periods Aching joints |
Look at the middle column. That is most of what women actually complain about, and it happens at both ends.
This is why guessing from symptoms does not work. It is also why one blood test does not settle it.
These are the genes I look at.
You do not need to memorize these. I just want you to see that they are real, specific things with real, specific jobs.
The estrogen pathway, gene by gene
| Gene | Its job | If yours runs slow or different |
|---|---|---|
| ESR1, ESR2 | The receptors. The locks estrogen fits into. | The signal may land differently than it does for someone else at the same level. |
| CYP19A1 | Aromatase. Turns other hormones into estrogen, including in fat tissue. | Affects how much estrogen you make. The strongest known genetic influence on estrogen levels. |
| CYP1A1, CYP1B1 | The first cut. Your liver can break estrogen down more than one way, and the pieces are not identical. | Shifts which pieces you make more of. CYP1B1 favors the harsher one. |
| COMT | Puts a small tag on those pieces so they can leave. Also clears your stress hormones. | The slower version makes 2 to 3 times less tagged product in the lab. It is also busy with adrenaline, so stress competes for it. |
| MTHFR | Supplies the raw material COMT uses to make those tags. | Less raw material available. One study found about 12 percent lower levels of the key ingredient. |
| GSTM1, GSTT1 | The cleanup crew for the harsher breakdown pieces. | Some people are missing these genes entirely. Cleanup may run leaner. |
Notice how they chain together. CYP1B1 makes a piece, COMT tags it, MTHFR supplies what COMT needs, GST cleans up what is left.
One slow step is manageable. Two or three slow steps stacked on top of each other is a different situation, and that is the part a symptom quiz will never tell you.
These genes are real and their jobs are established. What no gene test can do yet is predict exactly which symptom you will get, or guarantee how you will respond to hormone therapy. Anyone promising that is ahead of the science.
What your results do tell us is where to look first, and in what order to fix things. That is the difference between a plan and a guess.
Supporting the pathway is not the same as replacing the hormone.
This is the most important part, so I am going to say it plainly.
Nutrients help the machinery run. B vitamins, fiber, crucifers, all of that supports the steps above.
But none of it makes estrogen.
If your estrogen has genuinely dropped, no supplement is going to fill that gap. That is what hormone therapy is for, and that is a conversation with a prescriber.
In my opinion this is where a lot of women get stuck. They are handed a supplement plan when they needed hormones, or handed hormones with none of the clearance side supported. Both halves matter.
Why your genes matter even on HRT
If you start estrogen, your body still has to clear it. The same COMT, CYP and GST steps are still doing that job, at whatever speed you were born with.
That is why knowing your genetics before or during hormone therapy is useful. Not to decide whether you take it. That is your doctor's call. But to know what needs support while you do.
One thing genuinely worth asking your prescriber
Estrogen swallowed as a pill goes through your liver first, which raises clotting proteins. Through the skin, as a patch or gel, it mostly skips that trip.
In the French ESTHER study, the pill form carried about 4 times the clot risk of taking nothing, while the skin form showed no measurable increase. ACOG's own guidance tells doctors to weigh that.
What to do on your own, and what to ask me about first
Worth doing on your own
| Cut back on alcohol | Best evidence here by far. In a controlled study, 2 drinks a day raised estrogen about 27 percent. Free. |
| Fiber, 25 to 30 g a day | Estrogen leaves through your gut. Fiber keeps it moving. |
| Crucifers as food | Broccoli, cabbage, Brussels sprouts, several times a week. |
| Daily bowel movements | Gut bacteria can unwrap estrogen on its way out and send it back around. Keep things moving. |
| Track one full cycle | Length, flow, symptoms by day. More useful to your doctor than any single blood test. |
Ask me first. DIM and I3C, which lowered blood levels of tamoxifen's active form in a 12-month trial and should never be taken on tamoxifen without a prescriber's sign-off. Calcium-D-glucarate, which is sold hard for this and has no human study behind it. Licorice root hiding in "hormone balance" blends. Black cohosh if you have any liver history. High-dose B6, which can cause nerve damage.
Let's find out which one of these is yours.
You have spent enough time guessing. The genetic test maps the genes above, and the intake goes through your results next to what you actually eat, take, and feel. You come out with the 2 or 3 things that are yours to work on, in the order that makes sense for your body. Or start with the free Dirty Gene Test, which takes about 10 minutes.
This is one practitioner's opinion and a summary of public research. It is educational, not medical advice, not a diagnosis, and not a treatment plan for you specifically. Sarah is not a physician and does not diagnose, treat, or prescribe. Diagnosis and medication decisions belong with your licensed provider. Do not start, stop or change any medication because of anything here. If you take tamoxifen, an aromatase inhibitor, or any prescription, clear every supplement with your prescriber first. See a doctor promptly for bleeding between periods or after sex, very heavy periods, any bleeding after a full year without one, swelling or pain in one leg, chest pain, trouble breathing, or a new severe headache with visual aura.
Sources referenced
- Canonico M, et al. Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women: The ESTHER Study. Circulation, 2007;115(7):840-845. (ahajournals.org)
- ACOG. Postmenopausal Estrogen Therapy: Route of Administration and Risk of Venous Thromboembolism. Committee Opinion 556, reaffirmed 2020. (acog.org)
- Thomson CA, et al. A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Res Treat, 2017;165(1):97-107. (PMID 28560655)
- Reichman ME, et al. Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women. J Natl Cancer Inst, 1993;85:722-727. (PMID 8478958)
- Goldin BR, et al. Estrogen excretion patterns and plasma levels in vegetarian and omnivorous women. N Engl J Med, 1982;307:1542-1547. (PMID 7144835)
- Santoro N, et al. The Menopause Transition: Signs, Symptoms, and Management Options. J Clin Endocrinol Metab, 2021;106(1):1-15. (academic.oup.com)
- Obi N, et al. Estrogen metabolite ratio: is the 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio predictive for breast cancer? Int J Womens Health, 2011;3:37-51. (PMID 21339936)
- ACOG. Should I have hormone testing before starting hormone therapy? Reviewed December 2025. (acog.org)