Drug & supplement interaction

Peony + 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 Peony can interact with; the most serious is rated moderate. Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.

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

Peony and Drospirenone, Estetrol

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

Why Are There 4 Interactions?

Peony interacts with whole categories of medication. Drospirenone, Estetrol falls into 4 of those categories, so it can interact with Peony 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 1A2 (CYP1A2) SUBSTRATES

1 of 4

Why this applies to Drospirenone, Estetrol

Drospirenone, Estetrol falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Peony interacts with.

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. 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 birth control pill Nextstellis (drospirenone and estetrol). Lab and animal studies suggest peony may mildly slow down an enzyme called CYP1A2, which is one of the pathways your body uses to clear certain medicines. If that happens, the hormones in your pill could build up a little, which in theory might mean more of the usual side effects like nausea, breast tenderness, headaches, bloating, or mood changes.

But I want to keep this in perspective. This is only a theoretical concern based on test-tube work, and it has never been shown in real people. For most folks it likely won't cause a problem. Still, since peony has limited human evidence, it's worth a quick chat with your pharmacist or doctor before adding it, especially if you notice new symptoms.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang W, Tian DD, Zheng B, et al. Peony-glycyrrhiza decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models. Drug Metab Dispos 2015;43(7):1147-53. PubMed
Moderate

ESTROGENS

2 of 4

Drospirenone, Estetrol also falls under ESTROGENS.

Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.
In vitro and animal research shows that peony extract has estrogenic activity. Theoretically, peony might compete for estrogen receptors and/or cause additive 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 estetrol (a plant-like estrogen) with drospirenone, and it's mainly used for birth control. Here's the thing about peony: in lab dishes and animal studies, it seems to have some weak estrogen-like activity of its own. So in theory, taking large, concentrated amounts of peony alongside your pill could pile on a little extra estrogen effect. That might mean more of the usual estrogen-related nuisances, like breast tenderness, bloating, nausea, or headaches.

I want to be honest though: this is a theoretical concern based on test-tube and animal data, not real cases in people. The occasional culinary or tea amount is unlikely to matter. If you're using concentrated peony supplements regularly, just give your pharmacist or doctor a heads-up so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Xu Y, Li X, Chen T, et al. Radix Paeoniae Alba increases serum estrogen level and up-regulates estrogen receptor expression in uterus and vagina of immature/ovariectomized mice. Phytother Res. 2019;33(1):117-29. [RETRACTED].
Moderate

CONTRACEPTIVE DRUGS

3 of 4

Drospirenone, Estetrol also falls under CONTRACEPTIVE DRUGS.

Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.
In vitro and animal research shows that peony extract has estrogenic activity. Concomitant use might also increase the risk for estrogen-related adverse 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

Here's the situation with peony and your birth control pill, Nextstellis (which combines drospirenone and estetrol, a form of estrogen). In lab dishes and animal studies, peony seems to act a little like estrogen by latching onto the same receptors. The worry is mostly the other direction: that peony's own estrogen-like activity could add to your pill's estrogen and slightly raise the chance of estrogen-related side effects, like breast tenderness, bloating, nausea, headaches, or mood changes.

I want to be honest that this is theoretical. It comes from cell and animal research, not from real patients, so we don't truly know if it matters in everyday life. Still, since this is your contraception, it's worth a quick chat with your pharmacist or doctor before adding peony, especially in concentrated supplement form.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Xu Y, Li X, Chen T, et al. Radix Paeoniae Alba increases serum estrogen level and up-regulates estrogen receptor expression in uterus and vagina of immature/ovariectomized mice. Phytother Res. 2019;33(1):117-29. [RETRACTED].
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

4 of 4

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

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. 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 Nextstellis pill, which combines drospirenone and estetrol. Both hormones are broken down in part by a liver enzyme called CYP3A4. In test-tube studies, peony appears to weakly slow that same enzyme down. If that happened in your body, the hormones could clear a bit more slowly and build up slightly, which might mean more of the usual side effects like nausea, breast tenderness, mood changes, or spotting.

I want to be honest, though: this is only lab-based, theoretical data, and it has not been shown in real people. Food-sized amounts of peony are unlikely to matter, but concentrated supplements are harder to predict. If you'd like to use peony, just run it by your pharmacist or doctor first so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang W, Tian DD, Zheng B, et al. Peony-glycyrrhiza decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models. Drug Metab Dispos 2015;43(7):1147-53. 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

Peony Also Interacts With Other Medications

Peony has 810 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 810 No known interaction 2,020 (incl. Drospirenone, Estetrol)
Taking anything else?

Check Another of Your Medications Against Peony

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

Everything else you take

See Every Supplement That Interacts With Drospirenone, Estetrol

This page covers Peony 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 Peony as Part of a Dietary Supplement Product? Check It for Interactions

We hold 71 real supplement products containing Peony, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Peony. Your product may carry other ingredients that interact with Drospirenone, Estetrol too, on top of Peony — 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 Peony 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 Peony
Top 25%

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

29 days ago today
Medication Drospirenone, Estetrol
Top half

#873 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 Peony

What is Peony?

Peony
  • Menstrual cramps and irregular periods
  • Muscle cramps and spasms
  • Anxiety and stress
  • Inflammation and pain
  • Polycystic ovary syndrome (PCOS)

Peony root is a traditional Chinese medicine herb often used for menstrual problems, cramps, and inflammation, frequently as part of combination formulas. Human evidence for most uses is limited or preliminary, so it should not replace proven treatments. Talk to your pharmacist or doctor before using it, especially if you are pregnant, breastfeeding, or taking other medicines.

Read the full Peony monograph & all interactions
Keep checking

Other Drugs & Peony

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

0Major
810Moderate
0Minor
2,019No known interaction
810 Moderate 2,019 No interaction
Moderate

810 interactions

Showing 60 of 810 moderate interactions — see all 810 on the Peony page.

No interaction 2,019 drugs checked — show the list

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

Showing the 60 most looked-up of 2,019 medications checked with no known interaction — see the full Peony list.

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

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