Drug & supplement interaction

Echinacea + 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 2 drug categories that Echinacea can interact with; the most serious is rated moderate. Echinacea might inhibit the metabolism of CYP1A2 and increase plasma levels of some drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Echinacea and Estradiol, Norethindrone Acetate

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Echinacea interacts with whole categories of medication. Estradiol, Norethindrone Acetate falls into 2 of those categories, so it can interact with Echinacea in 2 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 2

Why this applies to Estradiol, Norethindrone Acetate

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

Echinacea might inhibit the metabolism of CYP1A2 and increase plasma levels of some drugs.
Echinacea appears to inhibit CYP1A2 enzymes in humans. Additionally, echinacea seems to increase plasma concentrations of caffeine, a CYP1A2 substrate, by around 30%. Theoretically, echinacea might increase levels of other drugs metabolized by CYP1A2.
Severity Moderate Likelihood Possible Evidence B

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 with Activella (estradiol plus norethindrone). Echinacea can mildly block a liver enzyme called CYP1A2, which helps process estrogen. If that enzyme slows down a bit, your estradiol could hang around at slightly higher levels than usual. In practice that might mean more of the typical estrogen side effects, like breast tenderness, bloating, nausea, headaches, or spotting.

I don't want you to lose sleep over this one. The strongest human evidence is for caffeine going up about 30 percent, and the estrogen effect here is mostly theoretical. For occasional, short-term echinacea use it's unlikely to cause real trouble. Still, if you plan to take it regularly or notice new symptoms, run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Gorski JC, Huang S, Zaheer NA, et al. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo.Clin Pharmacol Ther 2003;73 (Abstract PDII-A-8):P94. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

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

Echinacea may induce hepatic CYP3A4 and inhibit intestinal CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Several clinical trials have shown that taking echinacea for up to one month does not significantly affect the metabolism of various CYP3A4 substrates, including midazolam, docetaxel, etravirine, lopinavir-ritonavir, and darunavir-ritonavir. However, other clinical research shows that echinacea may increase the clearance of midazolam, suggesting that echinacea might induce CYP3A4. The discrepancy is thought to be due to differing effects of echinacea on intestinal versus hepatic CYP3A4 enzymes. Echinacea appears to induce hepatic CYP3A4 but inhibit intestinal CYP3A4. In some cases, these effects might cancel each other out, but in others, drug levels may be increased or decreased depending on the level of effect at hepatic and intestinal sites. The effect of echinacea on CYP3A4 activity may differ depending on the CYP3A4 substrate.
Severity Moderate Likelihood Possible Evidence B

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

The hormones in Activella, estradiol and norethindrone, are partly broken down by an enzyme called CYP3A4. Echinacea has a mixed effect on this enzyme: it may speed it up in the liver while slowing it in the gut. Because these pushes can pull in opposite directions, the real-world effect on your hormone levels is hard to predict and may be small for many people.

If echinacea nudges your hormone levels down, you could notice things like breakthrough bleeding or a return of menopause symptoms such as hot flashes. If levels edge up, side effects like breast tenderness, nausea, or bloating could become more noticeable. The clinical evidence here is limited and inconsistent, so this isn't a reason to panic. Still, it's worth a quick chat with your pharmacist or doctor before adding echinacea.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  2. Yale SH, Glurich I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 2005;11:433-9.
  3. Gorski JC, Huang S, Zaheer NA, et al. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo.Clin Pharmacol Ther 2003;73 (Abstract PDII-A-8):P94. PubMed
  4. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004;76:428-40. .
  5. Penzak, S. R., Robertson, S. M., Hunt, J. D., Chairez, C., Malati, C. Y., Alfaro, R. M., Stevenson, J. M., and Kovacs, J. A. Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy s
  6. Schroder-Aasen T, Molden G, Nilsen OG. In vitro inhibition of CYP3A4 by the multiherbal commercial product Sambucus Force and its main constituents Echinacea purpurea and Sambucus nigra. Phytother Res 2012;26(11):1606-13.
  7. Goey AK, Meijerman I, Rosing H, et al. The effect of Echinacea purpurea on the pharmacokinetics of docetaxel. Br J Clin Pharmacol 2013;76(3):467-74.
  8. Moltó J, Valle M, Miranda C, et al. Herb-drug interaction between Echinacea purpurea and etravirine in HIV-infected patients. Antimicrob Agents Chemother 2012;56(10):5328-31. PubMed
  9. Hansen TS, Nilsen OG. In vitro CYP3A4 metabolism: inhibition by Echinacea purpurea and choice of substrate for the evaluation of herbal inhibition. Basic Clin Pharmacol Toxicol 2008;103:445-9.

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

Echinacea Also Interacts With Other Medications

Echinacea has 814 moderate, 1 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 814 Minor 1 No known interaction 2,015 (incl. Estradiol, Norethindrone Acetate)
Taking anything else?

Check Another of Your Medications Against Echinacea

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

From our Q&A

Questions About Echinacea 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 Echinacea 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 Echinacea 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 Echinacea as Part of a Dietary Supplement Product? Check It for Interactions

We hold 350 real supplement products containing Echinacea, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Echinacea. Your product may carry other ingredients that interact with Estradiol, Norethindrone Acetate too, on top of Echinacea — 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 Echinacea 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 Echinacea
Top 5%

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

29 days ago today
Medication Estradiol, Norethindrone Acetate
Steady interest

#2,347 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 Echinacea

What is Echinacea?

Echinacea
  • Common cold
  • Flu and respiratory infections
  • Immune support
  • Sore throat
  • Wound and skin care (traditional)

Echinacea is a popular herb taken to help prevent or shorten the common cold, but study results are mixed and the overall benefit appears small at best. It is generally well tolerated for short-term use in most healthy adults, though people with allergies to daisy-family plants and those who are pregnant or breastfeeding should be cautious and talk to a pharmacist or doctor first.

Read the full Echinacea monograph & all interactions
Keep checking

Other Drugs & Echinacea

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

0Major
814Moderate
1Minor
2,014No known interaction
814 Moderate 1 Minor 2,014 No interaction
Moderate

814 interactions

Showing 60 of 814 moderate interactions — see all 814 on the Echinacea page.

Minor

1 interaction

No interaction 2,014 drugs checked — show the list

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

Showing the 60 most looked-up of 2,014 medications checked with no known interaction — see the full Echinacea list.

See the full Echinacea 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
Echinacea 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 Echinacea and Estradiol, Norethindrone Acetate Together: Common Questions

Can you take Echinacea 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 2 interactions listed for Echinacea and Estradiol, Norethindrone Acetate?
Estradiol, Norethindrone Acetate belongs to more than one drug category, and Echinacea 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 Echinacea 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

Still Have a Question About Estradiol, Norethindrone Acetate and Echinacea?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.