Drug & supplement interaction

Licorice + Drospirenone, Estetrol

Drospirenone, Estetrol brand name: Nextstellis.

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

Drospirenone, Estetrol falls into 4 drug categories that Licorice can interact with; the most serious is rated moderate. Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Licorice and Drospirenone, Estetrol

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Licorice interacts with whole categories of medication. Drospirenone, Estetrol falls into 4 of those categories, so it can interact with Licorice in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 4

Why this applies to Drospirenone, Estetrol

Drospirenone, Estetrol falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Licorice interacts with.

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity. Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity. However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species. Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.
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

Nextstellis combines two hormones, drospirenone and estetrol, and your body processes them partly through a liver enzyme called CYP3A4. Licorice can nudge that enzyme in either direction depending on the type, so the science here is genuinely mixed and mostly theoretical. If licorice speeds the enzyme up, your hormone levels could dip a bit, which in theory might make the pill slightly less reliable or cause breakthrough spotting. If it slows the enzyme, levels could edge higher.

There's a second wrinkle worth knowing: drospirenone is potassium-sparing, and regular (glycyrrhizin-containing) licorice can shift sodium and potassium too. I wouldn't panic over a cup of tea, but before using concentrated licorice supplements regularly, please check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kent UM, Aviram M, Rosenblat M, Hollenberg PF. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab Dispos 2002;30:709-15.. PubMed
  2. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  3. Tu, J. H., He, Y. J., Chen, Y., Fan, L., Zhang, W., Tan, Z. R., Huang, Y. F., Guo, D., Hu, D. L., Wang, D., and Hong-Hao Zhou. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol 2010;66(8):805-810. PubMed
  4. Li G, Simmler C, Chen L, et al. Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci. 2017;109:182-190. PubMed
Moderate

ESTROGENS

2 of 4

Drospirenone, Estetrol also falls under ESTROGENS.

Theoretically, licorice might increase or decrease the effects of estrogen therapy.
Theoretically, licorice might interfere with estrogen therapy due to estrogenic and anti-estrogenic effects.
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 with estetrol, an estrogen birth control pill. The concern here with licorice is mostly theoretical, and it comes from lab and animal studies, not solid human research. Licorice can act a little like estrogen in some tissues and block it in others, so in theory it might slightly nudge your estrogen effect up or down. We honestly can't predict which way for any one person.

One thing worth flagging: drospirenone can raise potassium, while real licorice (the glycyrrhizin kind) tends to lower it and raise blood pressure, so they pull in different directions on your body's salt balance. Occasional culinary amounts likely don't matter, but regular supplement doses might. Please check with your pharmacist or doctor before combining them, especially if you have blood pressure or kidney concerns.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause 2002;9:145-50. PubMed
  2. Francini-Pesenti F, Puato M, Piccoli A, Brocadello F. Liquorice-induced hypokalaemia and water retention in the absence of hypertension. Phytother Res 2008;22:563-5. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

3 of 4

Drospirenone, Estetrol also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
In vitro research shows that licorice can increase P-glycoprotein 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 gist for your Nextstellis (which combines drospirenone and estetrol, a birth control pill). Some lab work suggests licorice may rev up a transporter called P-glycoprotein. If that happens, it could nudge a bit less of these hormones into your system, which in theory might make the pill slightly less effective. Honestly, though, this is based only on test-tube and animal data, not real patients, so I wouldn't lose sleep over it.

One thing worth flagging: drospirenone can raise potassium, and large or long-term licorice use lowers potassium and bumps blood pressure, so they pull in opposite directions there. Occasional culinary licorice is unlikely to matter, but regular concentrated supplements deserve a quick chat with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang H, Dong L, Qu F, et al. Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism. Pharm Biol. 2020 Dec;58(1):352-356. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

4 of 4

Drospirenone, Estetrol also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, licorice might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that licorice induces CYP1A2 enzymes.
Severity Minor 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 situation with Nextstellis (which combines drospirenone and estetrol) and licorice. In lab studies, licorice appears to speed up an enzyme called CYP1A2. If that played out in real people, it could in theory clear this birth control pill a little faster and slightly lower its hormone levels. The worry would be weaker contraceptive protection or some breakthrough spotting.

That said, this is only a theoretical concern based on test-tube research, not real patient cases, and the official rating is minor. There's a separate point worth knowing: drospirenone can raise potassium, and licorice in large or long-term doses lowers potassium and can raise blood pressure, so they tug in different directions. If you want to use licorice regularly, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. 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

Licorice Also Interacts With Other Medications

Licorice has 976 moderate, 63 minor 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 976 Minor 63 No known interaction 1,791 (incl. Drospirenone, Estetrol)
Taking anything else?

Check Another of Your Medications Against Licorice

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

From our Q&A

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

We hold 4,721 real supplement products containing Licorice, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Licorice. Your product may carry other ingredients that interact with Drospirenone, Estetrol too, on top of Licorice — 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 Licorice 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 Licorice
Top 5%

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

29 days ago today
Medication Drospirenone, Estetrol
Top half

#1,162 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 Licorice

What is Licorice?

Licorice
  • Sore throat and cough
  • Heartburn and stomach upset
  • Mouth ulcers and digestive complaints
  • Inflammation
  • Traditional tonic/adrenal support

Licorice root is a traditional remedy used for sore throats, coughs, and digestive complaints, but solid human evidence is limited for most uses. Regular licorice contains glycyrrhizin, which can raise blood pressure and lower potassium when taken in large amounts or for a long time, so deglycyrrhizinated (DGL) products are often preferred. Talk to your pharmacist or doctor before using it, especially if you have high blood pressure, heart, or kidney problems.

Read the full Licorice monograph & all interactions
Keep checking

Other Drugs & Licorice

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

0Major
976Moderate
63Minor
1,790No known interaction
976 Moderate 63 Minor 1,790 No interaction
Moderate

976 interactions

Showing 60 of 976 moderate interactions — see all 976 on the Licorice page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Licorice page.

No interaction 1,790 drugs checked — show the list

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

Showing the 60 most looked-up of 1,790 medications checked with no known interaction — see the full Licorice list.

See the full Licorice 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
Licorice 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 Licorice and Drospirenone, Estetrol Together: Common Questions

Can you take Licorice 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 4 interactions listed for Licorice and Drospirenone, Estetrol?
Drospirenone, Estetrol belongs to more than one drug category, and Licorice 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 Licorice 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

Still Have a Question About Drospirenone, Estetrol and Licorice?

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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.