Drug & supplement interaction

Red Clover + Segesterone Acetate, Ethinyl Estradiol

Segesterone Acetate, Ethinyl Estradiol brand name: Annovera.

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

Segesterone Acetate, Ethinyl Estradiol 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?
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Interaction report

Red Clover and Segesterone Acetate, Ethinyl Estradiol

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. Segesterone Acetate, Ethinyl Estradiol 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 Segesterone Acetate, Ethinyl Estradiol

Segesterone Acetate, Ethinyl Estradiol 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

Annovera is a vaginal ring that releases two hormones, segesterone acetate (a progestin) and ethinyl estradiol (an estrogen), to prevent pregnancy. Red clover carries phytoestrogens, plant compounds that loosely mimic estrogen. On paper, these plant compounds could compete with the estrogen in your ring at the same receptors, which might slightly blunt how your body responds to the hormones.

It's important to know this is only a theoretical concern. There's no solid human evidence that red clover weakens birth control or causes pregnancy, and food amounts of clover are very unlikely to matter. Still, since reliable contraception is the goal here, I wouldn't gamble on it. Please check with your pharmacist or doctor before pairing concentrated red clover supplements with Annovera.

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

Segesterone Acetate, Ethinyl Estradiol 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 short version: the worry on file is that red clover might slow down a liver enzyme called CYP1A2, which helps process the estrogen part of Annovera (ethinyl estradiol). If that enzyme were blocked, estrogen levels could theoretically creep up, leading to things like nausea, breast tenderness, bloating, or headaches.

The good news is that this is mostly a lab-dish concern. When researchers actually gave people red clover isoflavones for two weeks, it did not change how the body handled a CYP1A2 test drug. So a real-world effect on your birth control is unlikely. Still, red clover has mild estrogen-like activity of its own, so it's 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

Segesterone Acetate, Ethinyl Estradiol 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

Annovera is a vaginal ring that releases two hormones, segesterone acetate and ethinyl estradiol, to prevent pregnancy. Both are handled by a liver enzyme called CYP3A4. The thinking here is that red clover might slow that enzyme a little, which could let hormone levels drift up. In theory, that could mean more of the usual estrogen-type effects like nausea, breast tenderness, bloating, or headache.

The good news: this is a very weak, mostly theoretical concern. In a real human study, red clover did not change levels of a CYP3A4 test drug at all. So a meaningful problem here is unlikely. Still, since these are hormones, it's worth a quick word with your pharmacist or doctor before adding red clover, especially given its plant-estrogen activity.

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, 823 minor known drug interactions in our database — the Segesterone Acetate, Ethinyl Estradiol one above is among them. If you take anything else, check it against the full list below.

Moderate 43 Minor 823 No known interaction 1,964 (incl. Segesterone Acetate, Ethinyl Estradiol)
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 Segesterone Acetate, Ethinyl Estradiol

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Segesterone Acetate, Ethinyl Estradiol page lists 229 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Beer (major), Grapefruit (major), Siberian Cocklebur (major), St. John's Wort (major) and Wine (major).

By severity: 5 major · 193 moderate · 31 minor.

From our pharmacist’s overview on the Segesterone Acetate, Ethinyl Estradiol page

“St. John's wort is the interaction I would explain first to anyone using Annovera (segesterone acetate with ethinyl estradiol, a vaginal ring for birth control).”

Reviewed by 2 · Jul 18, 2026

Open the Segesterone Acetate, Ethinyl Estradiol 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 Segesterone Acetate, Ethinyl Estradiol 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 Segesterone Acetate, Ethinyl Estradiol 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%

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

29 days ago today
Medication Segesterone Acetate, Ethinyl Estradiol
Steady interest

#1,971 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
823Minor
1,963No known interaction
43 Moderate 823 Minor 1,963 No interaction
Moderate

43 interactions

Minor

823 interactions

Showing 60 of 823 minor interactions — see all 823 on the Red Clover page.

No interaction 1,963 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 1,963 medications checked with no known interaction — see the full Red Clover list.

See the full Red Clover interactions page
See every supplement checked against Segesterone Acetate, Ethinyl Estradiol, 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 Segesterone Acetate, Ethinyl Estradiol supplement interactions › Every supplement checked against Segesterone Acetate, Ethinyl Estradiol, 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 Segesterone Acetate, Ethinyl Estradiol Together: Common Questions

Can you take Red Clover with Segesterone Acetate, Ethinyl Estradiol?
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 Segesterone Acetate, Ethinyl Estradiol?
Segesterone Acetate, Ethinyl Estradiol 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 Segesterone Acetate, Ethinyl Estradiol 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.