Drug & supplement interaction

Peony + Mestranol, Norethindrone

Mestranol, Norethindrone brand names: Necon 1/50, Ortho Novum 21, Ortho-Novum 1/50-28, Norinyl 1 50 21 Day, Ortho Novum 1 Plus 50, and others.

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

Mestranol, Norethindrone falls into 2 drug categories that Peony can interact with; the most serious is rated moderate. Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Peony and Mestranol, Norethindrone

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. Mestranol, Norethindrone 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

CONTRACEPTIVE DRUGS

1 of 2

Why this applies to Mestranol, Norethindrone

Mestranol, Norethindrone falls under CONTRACEPTIVE DRUGS — the group Peony interacts with.

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

Your birth control pill combines an estrogen (mestranol) with a progestin (norethindrone) to prevent pregnancy. The concern here is mostly on paper: in lab dishes and animal studies, peony root seems to act a little like estrogen and may compete at the same estrogen receptors. We don't have solid human studies showing this actually changes how well your pill works or how you feel.

In theory, peony could either nudge against your pill's estrogen activity or add to estrogen-type effects like breast tenderness, bloating, nausea, or spotting. Because this is only a theoretical worry, I wouldn't panic. Still, since reliable contraception matters, please run peony past your pharmacist or doctor before adding it, and don't stop your pill on your own.

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

2 of 2

Mestranol, Norethindrone 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

This birth control pill combines mestranol (which your body turns into the estrogen ethinyl estradiol) and norethindrone, a progestin. Both hormones are broken down in part by a liver enzyme called CYP3A4. Peony has been shown, in test-tube studies only, to mildly slow that same enzyme. If it did the same thing in people, your body might clear these hormones a little slower, leaving slightly higher levels around. In theory that could mean more estrogen-type side effects like nausea, breast tenderness, bloating, or spotting.

Here is the reassuring part: this is purely a theoretical, lab-based concern that has never been seen in humans, and the effect on the enzyme was described as weak to moderate. I wouldn't expect a real problem, but it's still smart to mention peony to your pharmacist or doctor before adding it.

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 Mestranol, Norethindrone 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. Mestranol, Norethindrone)
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 Mestranol, Norethindrone

This page covers Peony only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Mestranol, Norethindrone page lists 193 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 · 147 moderate · 40 minor.

Open the Mestranol, Norethindrone 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 Mestranol, Norethindrone 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 Mestranol, Norethindrone 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%

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

29 days ago today
Medication Mestranol, Norethindrone
Top half

#1,206 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 Mestranol, Norethindrone, 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 Mestranol, Norethindrone supplement interactions › Every supplement checked against Mestranol, Norethindrone, 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 Mestranol, Norethindrone Together: Common Questions

Can you take Peony with Mestranol, Norethindrone?
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 Mestranol, Norethindrone?
Mestranol, Norethindrone 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 Mestranol, Norethindrone 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.