Drug & supplement interaction

Eleuthero + Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate brand name: Activella.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Estradiol, Norethindrone Acetate falls into 3 drug categories that Eleuthero can interact with; the most serious is rated moderate. Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Eleuthero and Estradiol, Norethindrone Acetate

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Eleuthero interacts with whole categories of medication. Estradiol, Norethindrone Acetate falls into 3 of those categories, so it can interact with Eleuthero in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Eleuthero interacts with.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.
In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2. This effect has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for your Activella (estradiol with norethindrone). Part of how your body clears estrogen runs through a liver enzyme called CYP1A2. In lab dishes and animal studies, eleuthero appeared to slow that enzyme down. If that held true in people, your estrogen levels could drift a little higher, which in theory might mean more of the usual estrogen-type effects like breast tenderness, bloating, nausea, headaches, or mood changes.

The honest part: this has only been seen in test tubes and animals, never confirmed in humans, so it's very much a theoretical concern rather than something proven. I wouldn't lose sleep over it, but since you take this daily, it's worth a quick mention to your pharmacist or doctor before adding eleuthero.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harkey MR, Henderson GL, Zhou L, et al. Effects of Siberian ginseng (Eleutherococcus senticosus) on c-DNA-expressed P450 drug metabolizing enzymes. Alt Ther 2001;7:S14.
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 3

Estradiol, Norethindrone Acetate also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, eleuthero might increase levels of P-glycoprotein substrates.
In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein. However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Let's talk about pairing eleuthero with your Activella (estradiol and norethindrone). In a lab setting, eleuthero appears to slow down a transporter called P-glycoprotein, which is one of the pumps your body uses to move certain medicines along. The thinking is that if that pump is slowed, a little more of your hormone medicine could stay in your system. In theory, that might nudge up the usual estrogen-related effects, things like breast tenderness, bloating, nausea, or breakthrough spotting.

Here's the reassuring part: this is based only on test-tube research, not on real people, so we honestly don't know if it matters at all in everyday use. I wouldn't lose sleep over it. Still, it's worth a quick mention to your pharmacist or doctor so they can keep an eye on how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Takahashi T, Kaku T, Sato T, et al. Effects of Acanthopanax senticosus HARMS extract on drug transport in human intestinal cell line Caco-2. J Nat Med. 2010;64(1):55-62. PubMed
  2. Freye E, GLeske J. Siberian ginseng results in beneficial effects on glucose metabolism in diabetes type 2 patients: a double blind placebo-controlled study in comparison to panax ginseng. Int J Clin Nutr. 2013;1(1):11-17.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Estradiol, Norethindrone Acetate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

If you're taking Activella (estradiol with norethindrone) and thinking about eleuthero, here's the gist. The estrogen and progestin in this pill are partly broken down by a liver enzyme called CYP3A4. Lab and animal studies hinted that eleuthero might slow that enzyme down, which in theory could let your hormone levels nudge a little higher. That might mean more of the usual hormone-type effects like breast tenderness, bloating, nausea, or breakthrough spotting.

The good news: when researchers actually gave eleuthero to healthy people, it did not meaningfully change CYP3A4 activity. So this is mostly a theoretical, unlikely, and minor concern. Still, it's worth a quick mention to your pharmacist or doctor before adding the supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harkey MR, Henderson GL, Zhou L, et al. Effects of Siberian ginseng (Eleutherococcus senticosus) on c-DNA-expressed P450 drug metabolizing enzymes. Alt Ther 2001;7:S14.
  2. Donovan JL, DeVane CL, Chavin KD, et al. Siberian Ginseng (Eleutheroccus senticosus) Effects on CYP2D6 and CYP3A4 Activity in Normal Volunteers. Drug Metab Dispos 2003;31:519-22.. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Eleuthero Also Interacts With Other Medications

Eleuthero has 678 moderate, 461 minor known drug interactions in our database — the Estradiol, Norethindrone Acetate one above is among them. If you take anything else, check it against the full list below.

Moderate 678 Minor 461 No known interaction 1,691 (incl. Estradiol, Norethindrone Acetate)
Taking anything else?

Check Another of Your Medications Against Eleuthero

Covers the 2,830 medications we’ve checked against Eleuthero. Pick one to open its full report.

From our Q&A

Questions About Eleuthero or Estradiol, Norethindrone Acetate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Eleuthero or Estradiol, Norethindrone Acetate, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Estradiol, Norethindrone Acetate

This page covers Eleuthero only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Norethindrone Acetate page lists 212 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 171 moderate · 38 minor.

From our pharmacist’s overview on the Estradiol, Norethindrone Acetate page

“Activella pairs estradiol with norethindrone as hormone therapy, and because the treatment depends on steady hormone levels in the blood, supplements that raise or lower those levels warrant real scrutiny. Three of the 212 interacting ingredients rate major, and all three hit that weak point: St.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Norethindrone Acetate interaction page

One more smart check

Taking Eleuthero as Part of a Dietary Supplement Product? Check It for Interactions

We hold 3,795 real supplement products containing Eleuthero, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Eleuthero. Your product may carry other ingredients that interact with Estradiol, Norethindrone Acetate too, on top of Eleuthero — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Eleuthero and Estradiol, Norethindrone Acetate Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Eleuthero
Top 5%

#65 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Estradiol, Norethindrone Acetate
Steady interest

#2,227 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Eleuthero

What is Eleuthero?

Eleuthero
  • Fatigue and low energy
  • Physical and athletic performance
  • Stress resistance (adaptogen)
  • Immune support
  • Mental focus and alertness

Eleuthero is an herb traditionally used as an 'adaptogen' to fight fatigue, boost energy, and help the body handle stress. The scientific evidence behind these uses is limited and mixed, so it should not replace proven treatments. It is generally well tolerated short-term, but pregnant and breastfeeding people and those with certain conditions should avoid it or check with a healthcare provider first.

Read the full Eleuthero monograph & all interactions
Keep checking

Other Drugs & Eleuthero

Browse every other medication we’ve checked against Eleuthero — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
678Moderate
461Minor
1,690No known interaction
678 Moderate 461 Minor 1,690 No interaction
Moderate

678 interactions

Showing 60 of 678 moderate interactions — see all 678 on the Eleuthero page.

Minor

461 interactions

Showing 60 of 461 minor interactions — see all 461 on the Eleuthero page.

No interaction 1,690 drugs checked — show the list

We also checked Eleuthero against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,690 medications checked with no known interaction — see the full Eleuthero list.

See the full Eleuthero interactions page
See every supplement checked against Estradiol, Norethindrone Acetate, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Eleuthero monograph › Uses, safety, and every drug interaction in one place Estradiol, Norethindrone Acetate supplement interactions › Every supplement checked against Estradiol, Norethindrone Acetate, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Eleuthero and Estradiol, Norethindrone Acetate Together: Common Questions

Can you take Eleuthero with Estradiol, Norethindrone Acetate?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Eleuthero and Estradiol, Norethindrone Acetate?
Estradiol, Norethindrone Acetate belongs to more than one drug category, and Eleuthero interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Eleuthero and Estradiol, Norethindrone Acetate interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.