Drug & supplement interaction

Fennel + Drospirenone, Estetrol

Drospirenone, Estetrol brand name: Nextstellis.

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

Drospirenone, Estetrol falls into 3 drug categories that Fennel can interact with; the most serious is rated moderate. Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.

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

Fennel and Drospirenone, Estetrol

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

Why Are There 3 Interactions?

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

Moderate

CONTRACEPTIVE DRUGS

1 of 3

Why this applies to Drospirenone, Estetrol

Drospirenone, Estetrol falls under CONTRACEPTIVE DRUGS — the group Fennel interacts with.

Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.

Some constituents of fennel have estrogenic activity.
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

Nextstellis is a birth control pill that pairs drospirenone with estetrol, a plant-like estrogen. The concern here is purely theoretical: fennel contains compounds (like anethole) that can act a little like estrogen and may compete at the same receptors your pill works on. In theory, very high amounts of fennel might blunt the hormone signal and slightly weaken the pill's reliability.

I want to be honest, this is based on lab pharmacology, not real cases of pregnancies, so the risk looks low. Normal cooking and seasoning with fennel almost certainly won't matter. The caution is really about concentrated fennel supplements or fennel essential oil taken regularly. If you're using one of those, check with your pharmacist or doctor before relying on this pill alone.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Drospirenone, Estetrol also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.

In vitro research suggests that fennel inhibits CYP3A4 enzyme activity. 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

Nextstellis combines drospirenone and estetrol, two hormones in this birth control pill that your body partly clears using an enzyme called CYP3A4. In a test-tube setting, fennel appeared to slow that enzyme down. If that happened in real life, it could let these hormones build up a bit, which might mean more of the usual hormone-related effects like breast tenderness, nausea, bloating, or mood changes.

Here's the reassuring part: this was only seen in lab studies, never in actual people, so it's very much a theoretical concern. Eating fennel as a food or spice is unlikely to matter at all. Concentrated fennel supplements or the essential oil are the bigger question mark, so just run those past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. PubMed
  2. Subehan, Zaidi, S. F., Kadota, S., and Tezuka, Y. Inhibition on human liver cytochrome P450 3A4 by constituents of fennel (Foeniculum vulgare): identification and characterization of a mechanism-based inactivator. J Agric.Food Chem. 12-12-2007;55(25):101 PubMed
Moderate

ESTROGENS

3 of 3

Drospirenone, Estetrol also falls under ESTROGENS.

Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.

Some constituents of fennel have estrogenic activity.
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 deal with fennel and Nextstellis (your drospirenone and estetrol birth control pill). Fennel contains plant compounds, like anethole, that can act a little bit like estrogen in the body. In theory, large amounts could nudge in on the same estrogen receptors your pill works through. That's the worry on file.

I want to be honest with you though: this concern is theoretical, based on lab pharmacology, not on real cases of pills failing. Normal cooking and seasoning amounts of fennel are very unlikely to matter. The bigger question mark is concentrated fennel supplements or the essential oil taken daily. If you're thinking about those, just run it by your pharmacist or doctor first so nobody's guessing about your contraception.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.

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

Fennel Also Interacts With Other Medications

Fennel has 739 moderate known drug interactions in our database — the Drospirenone, Estetrol one above is among them. If you take anything else, check it against the full list below.

Moderate 739 No known interaction 2,091 (incl. Drospirenone, Estetrol)
Taking anything else?

Check Another of Your Medications Against Fennel

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

From our Q&A

Questions About Fennel or Drospirenone, Estetrol

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Fennel or Drospirenone, Estetrol, 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 Drospirenone, Estetrol

This page covers Fennel only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Drospirenone, Estetrol page lists 245 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 200 moderate · 39 minor.

From our pharmacist’s overview on the Drospirenone, Estetrol page

“The stakes with Nextstellis (drospirenone and estetrol) are the ones that come with any birth control pill, because an interaction that lowers its hormone levels can mean an unplanned pregnancy, and I would treat this list with genuine seriousness. Most of what is here changes how the body handles the hormones.”

Reviewed by 2 · Jul 18, 2026

Open the Drospirenone, Estetrol interaction page

One more smart check

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

We hold 2,219 real supplement products containing Fennel, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Fennel. Your product may carry other ingredients that interact with Drospirenone, Estetrol too, on top of Fennel — 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 Fennel and Drospirenone, Estetrol 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 Fennel
Top 10%

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

29 days ago today
Medication Drospirenone, Estetrol
Top half

#1,236 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 Fennel

What is Fennel?

Fennel
  • Digestive upset and bloating
  • Infant colic
  • Menstrual cramps
  • Cough and respiratory complaints
  • Breast milk support (traditional)

Fennel is a Mediterranean herb widely used as a food and spice, and traditionally taken for digestive complaints, colic, and menstrual cramps. Some small studies suggest possible benefit for certain stomach and menstrual symptoms, but the evidence is limited. It is generally well tolerated in food amounts, but concentrated supplements and the essential oil should be used with caution and after checking with your pharmacist or doctor.

Read the full Fennel monograph & all interactions
Keep checking

Other Drugs & Fennel

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

0Major
739Moderate
0Minor
2,090No known interaction
739 Moderate 2,090 No interaction
Moderate

739 interactions

Showing 60 of 739 moderate interactions — see all 739 on the Fennel page.

No interaction 2,090 drugs checked — show the list

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

Showing the 60 most looked-up of 2,090 medications checked with no known interaction — see the full Fennel list.

See the full Fennel interactions page
See every supplement checked against Drospirenone, Estetrol, 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
Fennel monograph › Uses, safety, and every drug interaction in one place Drospirenone, Estetrol supplement interactions › Every supplement checked against Drospirenone, Estetrol, 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 Fennel and Drospirenone, Estetrol Together: Common Questions

Can you take Fennel with Drospirenone, Estetrol?
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 Fennel and Drospirenone, Estetrol?
Drospirenone, Estetrol belongs to more than one drug category, and Fennel 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 Fennel and Drospirenone, Estetrol 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.