Drug & supplement interaction

Peony + Estradiol, Norgestimate

Estradiol, Norgestimate brand name: Ortho-Prefest.

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

Estradiol, Norgestimate falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Peony and Estradiol, Norgestimate

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

Why Are There 2 Interactions?

Peony interacts with whole categories of medication. Estradiol, Norgestimate falls into 2 of those categories, so it can interact with Peony 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, Norgestimate

Estradiol, Norgestimate 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 if you take Ortho-Prefest (estradiol plus norgestimate) and are curious about peony root. The estrogen part of this combo is partly handled by a liver enzyme called CYP1A2. In lab and animal studies, peony seems to gently slow that enzyme down. In theory, that could let a little more estrogen linger in your system, which might mean more of the usual hormone-related effects like breast tenderness, bloating, nausea, headaches, or breakthrough spotting.

I want to be straight with you though: this is only test-tube and animal data, and it has not been shown in real people. For most folks the effect is likely small. Still, it's worth a quick chat with your pharmacist or doctor before adding a concentrated peony supplement.

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 2

Estradiol, Norgestimate 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

Here's the gist with Ortho-Prefest, which is a combination of estradiol (an estrogen) and the progestin norgestimate, used for hormone replacement during menopause. Lab and animal studies suggest peony root has some weak estrogen-like activity of its own. The thought is that taking large amounts of peony alongside your hormone therapy could either add to your estrogen effects or compete at the same receptors, so the practical result is a bit unpredictable.

I want to be honest: this is theoretical, based on test-tube and animal data, not real patient cases. If anything shifted, you might notice things like breast tenderness, bloating, nausea, headaches, or spotting. Small culinary or short-term traditional doses are unlikely to matter much. Before adding a concentrated peony supplement, just check with your pharmacist or doctor first.

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].

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 Estradiol, Norgestimate 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. Estradiol, Norgestimate)
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 Estradiol, Norgestimate

This page covers Peony only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Norgestimate page lists 159 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), Adrafinil (moderate) and African Wild Potato (moderate).

By severity: 3 major · 126 moderate · 30 minor.

From our pharmacist’s overview on the Estradiol, Norgestimate page

“Ortho-Prefest pairs estradiol with norgestimate, a hormone therapy most often prescribed for menopause symptoms, and its interaction list warrants genuine care rather than a quick skim. Of the 159 supplements and herbs on file, three carry a major rating, and all involve common products.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Norgestimate 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 Estradiol, Norgestimate 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 Estradiol, Norgestimate 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%

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

29 days ago today
Medication Estradiol, Norgestimate
Top half

#944 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 Estradiol, Norgestimate, 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 Estradiol, Norgestimate supplement interactions › Every supplement checked against Estradiol, Norgestimate, 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 Estradiol, Norgestimate Together: Common Questions

Can you take Peony with Estradiol, Norgestimate?
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 Peony and Estradiol, Norgestimate?
Estradiol, Norgestimate 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 Estradiol, Norgestimate 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.