Drug & supplement interaction

Red Clover + Drospirenone, Estetrol

Drospirenone, Estetrol brand name: Nextstellis.

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

Drospirenone, Estetrol falls into 3 drug categories that Red Clover can interact with; the most serious is rated moderate. Theoretically, concomitant use of large amounts of red clover might interfere with estrogen therapy.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Red Clover and Drospirenone, Estetrol

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

Why Are There 3 Interactions?

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

Moderate

ESTROGENS

1 of 3

Why this applies to Drospirenone, Estetrol

Drospirenone, Estetrol falls under ESTROGENS — the group Red Clover interacts with.

Theoretically, concomitant use of large amounts of red clover might interfere with estrogen therapy.
Red clover contains phytoestrogens which might have estrogenic activity in some people. Theoretically, red clover might compete for estrogen receptors and interfere with estrogen-containing drug therapy.
Severity Moderate Likelihood Probable Evidence D

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Nextstellis combines drospirenone with estetrol, a plant-based form of estrogen, and it's used as a daily birth control pill. Red clover carries phytoestrogens, which are weak plant compounds that loosely mimic estrogen. The concern here is mostly on paper: in theory, these compounds could nudge in on the same estrogen receptors your pill works through and slightly muddy its hormonal signal.

The good news is this interaction is theoretical only, based on how the chemicals behave, not on real cases of pills failing. The phytoestrogens in red clover are far weaker than the estrogen in your medication, so a meaningful change is unlikely. Still, since this is birth control, I'd keep your doctor or pharmacist in the loop before adding a concentrated red clover supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr 1997;17:353-81. PubMed
  2. Wuttke W, Jarry H, Seidlova-Wuttke D. Plant-derived alternative treatments for the aging male: facts and myths. Aging Male 2010;13(2):75-81. PubMed
  3. Villaseca P. Non-estrogen conventional and phytochemical treatments for vasomotor symptoms: what needs to be known for practice. Climacteric 2012;15(2):115-124. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

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

Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.
In vitro evidence shows that red clover inhibits CYP1A2. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine, a CYP1A2 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the simple version for Nextstellis (drospirenone and estetrol). In a test tube, red clover can slow down a liver enzyme called CYP1A2, which is one of the pathways your body uses to clear certain medicines. The worry on paper is that this could let drug levels creep up a bit. In theory, higher hormone levels could mean more of the usual side effects like breast tenderness, nausea, headaches, or spotting.

But here's the reassuring part: this is only lab-dish evidence, and when red clover was actually tested in people, it didn't change how the body handled a CYP1A2 marker drug. So a real-world problem is unlikely. That said, since red clover acts like a weak plant estrogen, it's still worth a quick chat with your pharmacist or doctor before combining the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

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

Theoretically, red clover might increase levels of drugs metabolized by CYP3A4; however, a small clinical study found no effect.
In vitro evidence shows that red clover might inhibit CYP3A4 isoenzymes. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of alprazolam, a CYP3A4 probe substrate.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for your Nextstellis (drospirenone with estetrol): in the lab, red clover looked like it might slow down CYP3A4, the liver enzyme that helps clear the hormones in your pill. If that happened in real life, hormone levels could nudge up a bit, which in theory might mean more of the usual side effects like breast tenderness, nausea, bloating, or spotting.

But here's the reassuring part: when researchers actually tested red clover in people, it did not meaningfully change how the body handled a CYP3A4 drug. So this concern stays mostly theoretical and is considered minor and unlikely. Neither hormone here is a prodrug, so you don't lose effectiveness. Still, since red clover acts a bit like estrogen, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  3. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. 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

Red Clover Also Interacts With Other Medications

Red Clover has 43 moderate, 825 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 43 Minor 825 No known interaction 1,962 (incl. Drospirenone, Estetrol)
Taking anything else?

Check Another of Your Medications Against Red Clover

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

Everything else you take

See Every Supplement That Interacts With Drospirenone, Estetrol

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

We hold 1,480 real supplement products containing Red Clover, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Red Clover. Your product may carry other ingredients that interact with Drospirenone, Estetrol too, on top of Red Clover — 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 Red Clover 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 Red Clover
Top 25%

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

29 days ago today
Medication Drospirenone, Estetrol
Steady interest

#1,641 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 Red Clover

What is Red Clover?

Red Clover
  • Menopause symptoms (hot flashes)
  • High cholesterol
  • Bone health/osteoporosis
  • Skin and hair concerns
  • Women's health

Red clover is a plant rich in isoflavones (plant compounds with weak estrogen-like activity) that is most often used for menopause symptoms like hot flashes. The evidence is mixed and generally weak, with some studies showing modest benefit and others showing none. Because of its hormone-like effects, it's not for everyone—talk with your pharmacist or doctor before trying it, especially if you have a hormone-sensitive condition.

Read the full Red Clover monograph & all interactions
Keep checking

Other Drugs & Red Clover

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

0Major
43Moderate
825Minor
1,961No known interaction
43 Moderate 825 Minor 1,961 No interaction
Moderate

43 interactions

Minor

825 interactions

Showing 60 of 825 minor interactions — see all 825 on the Red Clover page.

No interaction 1,961 drugs checked — show the list

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

Showing the 60 most looked-up of 1,961 medications checked with no known interaction — see the full Red Clover list.

See the full Red Clover 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
Red Clover 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 Red Clover and Drospirenone, Estetrol Together: Common Questions

Can you take Red Clover 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 Red Clover and Drospirenone, Estetrol?
Drospirenone, Estetrol belongs to more than one drug category, and Red Clover 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 Red Clover 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 Red Clover?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.